1,511 results match your criteria Toxicity Isoniazid


Solid lipid nanoparticles for ocular delivery of isoniazid: evaluation, proof of concept and in vivo safety & kinetics.

Nanomedicine (Lond) 2019 Feb 29;14(4):465-491. Epub 2019 Jan 29.

University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.

Aim: Evaluation of solid lipid nanoparticles (SLNs) for ocular delivery of isoniazid (INH).

Materials & Methods: INH-SLNs were characterized for morphological, thermal, crystalline and nuclear magnetic resonance properties. In vitro release and ex vivo corneal permeability of INH-SLNs was also evaluated. Read More

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http://dx.doi.org/10.2217/nnm-2018-0278DOI Listing
February 2019
1 Read

Medical treatment for urogenital tuberculosis (UGTB).

Authors:
Christian Wejse

GMS Infect Dis 2018 9;6:Doc04. Epub 2018 Aug 9.

Department of Infectious Diseases/Center for Global Health, Dept of Public Health, Aarhus University, Denmark.

Urogenital tuberculosis (UGTB) should in general be treated as pulmonary TB with a four-drug regimen of Isoniazid, Rifampicin, Ethambutol and Pyrazinamide for a total of 6 months, Ethambutol and Pyrazinamide only the first two months. Some patients may need longer treatment (cavitary disease, kidney abscess/malfunction, HIV co-infection). Treatment of multi-drug resistant tuberculosis (MDR-TB) requires use of long-term intravenous treatment with aminoglycosides and other drugs with considerable toxicity for 18-24 months. Read More

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http://dx.doi.org/10.3205/id000039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301712PMC
August 2018
4 Reads

Pharmacokinetics of isoniazid in Indian children with tuberculosis on daily treatment.

Int J Tuberc Lung Dis 2019 Jan 20;23(1):52-57. Epub 2018 Dec 20.

Department of Clinical Pharmacology, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai, India.

Objective: To assess the pharmacokinetics of isoniazid (INH) at 10 mg/kg/day among Indian children.

Methods: INH levels were estimated using liquid chromatography-tandem mass spectroscopy in 35 children aged 1-15 years on daily anti-tuberculosis treatment. Blood samples were collected 0, 1, 2, 3, 6 and 24 h after INH administration. Read More

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http://dx.doi.org/10.5588/ijtld.18.0463DOI Listing
January 2019

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives.

J Clin Transl Res 2018 28;4(1). Epub 2018 May 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, US.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. Read More

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http://dx.doi.org/10.18053/jctres.04.201801.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261533PMC
May 2018
4 Reads

Efficacy Versus Hepatotoxicity of High-dose Rifampin, Pyrazinamide, and Moxifloxacin to Shorten Tuberculosis Therapy Duration: There Is Still Fight in the Old Warriors Yet!

Clin Infect Dis 2018 Nov;67(suppl_3):S359-S364

Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.

Background: One approach that could increase the efficacy and reduce the duration of antituberculosis therapy is pharmacokinetics/pharmacodynamics-based optimization of doses. However, this could increase toxicity.

Methods: We mimicked the concentration-time profiles achieved by human equivalent doses of moxifloxacin 800 mg/day, rifampin 1800 mg/day, and pyrazinamide 4000 mg/day (high-dose regimen) vs isoniazid 300 mg/day, rifampin 600 mg/day, and pyrazinamide 2000 mg/day (standard therapy) in bactericidal and sterilizing effect studies in the hollow fiber system model of tuberculosis (HFS-TB). Read More

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http://dx.doi.org/10.1093/cid/ciy627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260156PMC
November 2018
5 Reads

Roles of Cytochrome P450 in Metabolism of Ethanol and Carcinogens.

Adv Exp Med Biol 2018 ;1032:15-35

Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.

Cytochrome P450 (P450) enzymes are involved in the metabolism of carcinogens, as well as drugs, steroids, vitamins, and other classes of chemicals. P450s also oxidize ethanol, in particular P450 2E1. P450 2E1 oxidizes ethanol to acetaldehyde and then to acetic acid, roles also played by alcohol and aldehyde dehydrogenases. Read More

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http://dx.doi.org/10.1007/978-3-319-98788-0_2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371814PMC
January 2018
11 Reads

Conjugation of a 5-nitrofuran-2-oyl moiety to aminoalkylimidazoles produces non-toxic nitrofurans that are efficacious in vitro and in vivo against multidrug-resistant Mycobacterium tuberculosis.

Eur J Med Chem 2018 Sep 29;157:1115-1126. Epub 2018 Aug 29.

Saint Petersburg Research Institute of Phthisiopulmonology, 2-4 Ligovsky Prospekt, Saint Petersburg, 191036, Russian Federation.

Within the general nitrofuran carboxamide chemotype, chimera derivatives incorporating diversely substituted imidazoles attached via an alkylamino linker were synthesized. Antimycobacterial evaluation against drug-sensitive M. tuberculosis H37Rv strain identified five active druglike compounds which were further profiled against patient-derived M. Read More

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http://dx.doi.org/10.1016/j.ejmech.2018.08.068DOI Listing
September 2018
10 Reads

Expression and genotype-dependent catalytic activity of N-acetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1.

Biochem Pharmacol 2018 Oct 25;156:340-347. Epub 2018 Aug 25.

Translational and Molecular Medicine Department, Research Center for Health Sciences and Biomedicine, Autonomous University of San Luis Potosí, Mexico; Chemical Sciences School, Autonomous University of San Luis Potosí, Mexico. Electronic address:

N-acetyltransferase 2 (NAT2) catalyzes the biotransformation of numerous arylamine and hydrazine drugs and carcinogens. Genetic polymorphisms of NAT2 modify drug efficacy and toxicity and susceptibility to diseases such as cancer and type 2 diabetes. Expression of NAT2 has been documented in the liver and gastrointestinal tract but not in other tissues. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.08.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350916PMC
October 2018
3 Reads

[Study on cytotoxicity of three-dimensional printed β-tricalcium phosphate loaded poly (lactide-co-glycolide) anti-tuberculosis drug sustained release microspheres and its effect on osteogenic differentiation of bone marrow mesenchymal stem cells].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2018 09;32(9):1131-1136

Department of Orthopedics, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou Gansu, 730000,

Objective: To study the effect of three-dimensional (3D) printed β-tricalcium phosphate (β-TCP) scaffold loaded poly (lactide-co-glycolide) (PLGA) anti-tuberculosis drug sustained release microspheres on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and its cytotoxicity.

Methods: Isoniazid and rifampicin/PLGA sustained release microspheres were prepared by W/O/W multiple emulsion method. The β-TCP scaffolds were prepared by 3D printing technique. Read More

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http://dx.doi.org/10.7507/1002-1892.201803067DOI Listing
September 2018
5 Reads

Spray-dried fucoidan microparticles for pulmonary delivery of antitubercular drugs.

J Microencapsul 2018 Jun;35(4):392-405

a Centre for Biomedical Research , University of Algarve , Faro , Portugal.

Pulmonary tuberculosis accounts for 80% of cases and the delivery of antitubercular drugs into the lungs allows targeting the infected organ and, possibly, reducing systemic drug toxicity. This work aimed at using fucoidan as matrix of inhalable microparticles that associate two first-line antitubercular drugs, for an application in pulmonary tuberculosis therapy. Fucoidan is composed of fucose and sulphated sugar residues, moieties described as being recognised by surface receptors of alveolar macrophages, which host mycobacteria. Read More

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http://dx.doi.org/10.1080/02652048.2018.1513089DOI Listing
June 2018
1 Read

Synthesis and evaluation of substituted 3-cinnamoyl-4-hydroxy-pyran-2-one (CHP) in pursuit of new potential antituberculosis agents.

Medchemcomm 2018 Jan 6;9(1):165-172. Epub 2017 Dec 6.

Academy of Scientific and Innovative Research , Indian Institute of Integrative Medicine (CSIR) , Sanatnagar , Srinagar , Jammu and Kashmir 190005 , India . Email:

Tuberculosis is an ever-evolving infectious disease that urgently needs new drugs. In the search for new antituberculosis agents, a library of 3-cinnamoyl-4-hydroxy-6-methyl-2-pyran-2-ones (CHPs) () was synthesized and evaluated against a standard virulent laboratory strain of H37Rv. Out of 25 compounds, , , and ( and ) showed least, moderate, good and appreciable activities, respectively, based on minimum inhibitory concentrations (MICs). Read More

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http://dx.doi.org/10.1039/c7md00366hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072353PMC
January 2018
5 Reads

Synthesis and Spectrum of Biological Activities of Novel N-arylcinnamamides.

Int J Mol Sci 2018 Aug 7;19(8). Epub 2018 Aug 7.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia.

A series of sixteen ring-substituted -arylcinnamamides was prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against , three methicillin-resistant strains, H37Ra, , and . Several of the tested compounds showed antistaphylococcal, antitubercular, and antifungal activities comparable with or higher than those of ampicillin, isoniazid, and benomyl. Read More

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http://dx.doi.org/10.3390/ijms19082318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121455PMC
August 2018
3 Reads

New Ways to Treat Tuberculosis Using Dendrimers as Nanocarriers.

Pharmaceutics 2018 Jul 26;10(3). Epub 2018 Jul 26.

Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, BP 44099, 31077 Toulouse CEDEX 4, France.

Tuberculosis (TB) is a contagious infection that usually attacks not only the lungs, but also brain and spine. More than twenty drugs have been developed for the treatment of TB, but most of them were developed some years ago. They are used in different combinations. Read More

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http://dx.doi.org/10.3390/pharmaceutics10030105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161254PMC
July 2018
6 Reads

Interferon-gamma release assay for tuberculosis screening of solid-organ transplant recipients is cost-effective.

Authors:
A Kowada

J Infect 2019 Jan 24;78(1):58-65. Epub 2018 Jul 24.

General Affairs Department, Ota City Office, Tokyo, Japan. Electronic address:

Objectives: Tuberculosis (TB) is a serious infectious disease with high mortality for solid-organ transplantation. Preventive therapy of latent tuberculosis infection (LTBI) has been considered to reduce TB risk and improve outcomes of transplantation. The aim of this study was to evaluate the cost-effectiveness of the interferon-gamma release assays (IGRAs); QuantiFERON-TB Gold in-Tube (QFT) and T-SPOT. Read More

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http://dx.doi.org/10.1016/j.jinf.2018.07.003DOI Listing
January 2019
7 Reads

Genipin-crosslinked carboxymethyl chitosan nanogel for lung-targeted delivery of isoniazid and rifampin.

Carbohydr Polym 2018 Oct 7;197:403-413. Epub 2018 Jun 7.

Department of Light Chemical Engineering, Guangdong Polytechnic, Foshan 528041, PR China. Electronic address:

Lung-targeted genipin-crosslinked deacetylated chitosan (GEN-CS)/isoniazid (INH)/rifampin (RMP) nanogel particles (NGPs) were prepared as a treatment for tuberculosis caused by multidrug-resistant Mycobacterium tuberculosis (MTB) to surmount the undesirable side effects and decrease the cytotoxicity of INH and RMP when being against MTB. The size, morphology, in vitro release property, long-term antibacterial performance, stability, in vitro cytotoxicity, in vivo toxicity, and in vivo release property of GEN-CS/INH/RMP NGPs inhalation powder were investigated. The results showed that the GEN-CS/INH/RMP NGPs inhalation powder exhibited extended antibacterial activity because of its long-term release of INH and RMP. Read More

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http://dx.doi.org/10.1016/j.carbpol.2018.06.034DOI Listing
October 2018
13 Reads

Toxicity associated with tuberculosis chemotherapy in the REMoxTB study.

BMC Infect Dis 2018 Jul 11;18(1):317. Epub 2018 Jul 11.

University of St Andrews Medical School, St Andrews, UK.

Background: The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin.

Methods: All grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Read More

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http://dx.doi.org/10.1186/s12879-018-3230-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042413PMC
July 2018
8 Reads

Efficacy and Safety of High-Dose Rifampin in Pulmonary Tuberculosis. A Randomized Controlled Trial.

Am J Respir Crit Care Med 2018 09;198(5):657-666

9 Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.

Rationale: We examined whether increased rifampin doses could shorten standard therapy for tuberculosis without increased toxicity.

Objectives: To assess the differences across three daily oral doses of rifampin in change in elimination rate of Mycobacterium tuberculosis in sputum and frequency of rifampin-related adverse events.

Methods: We conducted a blinded, randomized, controlled phase 2 clinical trial of 180 adults with new smear-positive pulmonary tuberculosis, susceptible to isoniazid and rifampin. Read More

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http://dx.doi.org/10.1164/rccm.201712-2524OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118011PMC
September 2018
4 Reads

Berberis aristata Ameliorates Testicular Toxicity Induced by Combination of First-Line Tuberculosis Drugs (Rifampicin + Isoniazid + Pyrazinamide) in Normal Wistar Rats.

J Diet Suppl 2018 Jun 28:1-14. Epub 2018 Jun 28.

a Department of Zoology , Panjab University , Chandigarh , India.

First-line antituberculosis drugs, namely, isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA), contribute to diverse pathological complications. Testicular toxicity is one such complication. Berberis aristata DC is an herb with potentially curative characteristics. Read More

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http://dx.doi.org/10.1080/19390211.2018.1470127DOI Listing
June 2018
7 Reads

Interfacial Phenomenon Based Biocompatible Alginate-Chitosan Nanoparticles Containing Isoniazid and Pyrazinamide.

Pharm Nanotechnol 2018 ;6(3):209-217

School of Pharmacy, BBD University, Lucknow (UP), India.

Background: Tuberculosis (TB) is one of the major health challenge in the world. The current treatment of TB needs daily administration of combined drug therapy for six or more months. Sometime non-adherence and less bioavailability from current therapy develops multidrug resistance, as a result, high dose requirement and subsequent intolerable toxicity are seen. Read More

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http://dx.doi.org/10.2174/2211738506666180625120038DOI Listing
January 2019
6 Reads

Isoniazid-induced hepatotoxicity and neurotoxicity in rats investigated by H NMR based metabolomics approach.

Toxicol Lett 2018 Oct 21;295:256-269. Epub 2018 Jun 21.

Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei Street, Nanjing 210094, PR China. Electronic address:

Isoniazid (INH) is a well-known therapeutic and preventive agent against tuberculosis. However, high rates of side effects with various symptoms concerning hepatotoxicity and neurotoxicity have been reported, hindering its wide and safe application in clinic. In this investigation, rats were intoxicated with INH by gavage at doses of 200 and 400 mg/kg for 7 consecutive days to develop a rat model of acute INH-induced toxicity, which was investigated by a H NMR-based metabolomics complemented with clinical assays, histopathological inspection and western blotting. Read More

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http://dx.doi.org/10.1016/j.toxlet.2018.05.032DOI Listing
October 2018
13 Reads

Latent tuberculosis infection: Opportunities and challenges.

Respirology 2018 10 14;23(10):893-900. Epub 2018 Jun 14.

Denver Health and Hospital Authority, Denver Public Health Department, CO, USA.

Diagnosing and treating latent tuberculosis (TB) infection (LTBI) is recognized by the World Health Organization as an important strategy to accelerate the decline in global TB and achieve TB elimination. Even among low-TB burden countries that have achieved high rates of detection and successful treatment for active TB, a number of barriers have prevented implementing or expanding LTBI treatment programmes. Of those infected with TB, relatively few will develop active disease and the current diagnostic tests have a low predictive value. Read More

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http://dx.doi.org/10.1111/resp.13346DOI Listing
October 2018
3 Reads

Hepatoprotective effect of lawsone on rifampicin-isoniazid induced hepatotoxicity in in vitro and in vivo models.

Environ Toxicol Pharmacol 2018 Jul 15;61:87-94. Epub 2018 May 15.

Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O Box 2455, Riyadh 11451, Saudi Arabia. Electronic address:

The Drug-induced liver injury is one of the common unfavourable impacts, which seriously affects any drug therapy. This study documented the hepatoprotective efficacy of lawsone, the major bioactive naphthoquinone present in Lawsonia inermis L. (Lythraceae) using in vitro and in vivo models. Read More

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http://dx.doi.org/10.1016/j.etap.2018.05.006DOI Listing
July 2018
10 Reads
1.862 Impact Factor

Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity.

J Integr Med 2018 07 8;16(4):263-272. Epub 2018 May 8.

Histopathology Laboratory, Braithwaite Memorial Specialist Hospital, 50001 Rivers State, Nigeria; Medical Laboratory Science Department, Faculty of Science, Rivers State University of Science and Technology, Nkpoku Oroworukwo, Port Harcourt, PMB 5080 Rivers State, Nigeria.

Objectives: The aim of this study is to evaluate the hepatoprotective effect of Lasianthera africana (Icacinaceae) against isoniazid (INH) and rifampicin (RIF)-induced liver damage in rats.

Methods: The hepatoprotective effects of hot aqueous L. africana (HALA) leaf extract (0. Read More

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http://dx.doi.org/10.1016/j.joim.2018.05.001DOI Listing
July 2018
3 Reads

High-throughput toxicity testing of chemicals and mixtures in organotypic multi-cellular cultures of primary human hepatic cells.

Toxicol In Vitro 2018 Sep 8;51:83-94. Epub 2018 May 8.

Department of Chemical Engineering, Virginia Tech, Suite 245 Goodwin Hall, 635 Prices Fork Road, Blacksburg, VA 24061, USA; ICTAS Center for Systems Biology of Engineered Tissue, Virginia Tech, 333 Kelly Hall, 325 Stanger Street, Blacksburg, VA 24061, USA; School of Biomedical Engineering and Sciences, Virginia Tech, 333 Kelly Hall, 325 Stanger Street, Blacksburg, VA 24061, USA. Electronic address:

High-throughput screening (HTS) of liver toxicants can bridge the gap in understanding adverse effects of chemicals on humans. Toxicity testing of mixtures is time consuming and expensive, since the number of possible combinations increases exponentially with the number of chemicals. The combination of organotypic culture models (OCMs) and HTS assays can lead to the rapidly evaluation of chemical toxicity in a cost and time-effective manner while prioritizing chemicals that warrant additional investigation. Read More

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http://dx.doi.org/10.1016/j.tiv.2018.05.006DOI Listing
September 2018
6 Reads

Hepatoprotective Evaluation of against Drug-induced Hepatotoxicity of Antitubercular Agents in Rats.

Pharmacogn Mag 2018 Apr-Jun;14(54):180-185. Epub 2018 Apr 10.

Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India.

Background: Medicinal herbs are significantly effective against a variety of liver disorders and was traditionally used for the treatment of anti-inflammatory, pain disorder, and various types of hepatic ailment.

Objective: The purpose of this study was to evaluate the hepatoprotective activity of fruit peel extract against antitubercular drugs (isoniazid + rifampicin [INH + RIF])-induced hepatotoxicity in rats.

Materials And Methods: Liver toxicity was induced by INH + RIF at a dose level of 50 mg/kg each, intraperitoneally. Read More

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http://dx.doi.org/10.4103/pm.pm_237_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909312PMC
April 2018
3 Reads

A proposed management algorithm for late-onset efavirenz neurotoxicity.

S Afr Med J 2018 Mar 28;108(4):271-274. Epub 2018 Mar 28.

Division of Neurology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa.

A high proportion of HIV-positive patients in South Africa receive concomitant efavirenz (EFV) and isoniazid (INH) therapy. EFV is metabolised in the liver via CYP2B6, and genetic polymorphism of CYP2B6 is known to result in slowed metabolism of the drug. INH is also metabolised in the liver, causing inhibition of a pathway that plays an important role in slow EFV metabolisers. Read More

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http://dx.doi.org/10.7196/SAMJ.2017.v108i4.12914DOI Listing
March 2018
2 Reads

Discovery of Novel Enhancers of Isoniazid Toxicity in .

Molecules 2018 Apr 4;23(4). Epub 2018 Apr 4.

Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany.

The number of effective first-line antibiotics for the treatment of infection is strongly limited to a few drugs. Due to emerging resistance against those drugs, second- and third-line antibiotics have been established in therapy with certain problems and also increasing mycobacterial resistance. An alternative to such novel drugs or combined therapeutic regimes which may reduce resistance development is finding enhancers of mycobacterial drug effectiveness, especially enhancers that counteract causative resistance mechanisms. Read More

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http://www.mdpi.com/1420-3049/23/4/825
Publisher Site
http://dx.doi.org/10.3390/molecules23040825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017859PMC
April 2018
9 Reads

Synthesis and evaluation of novel coumarin-oxime ethers as potential anti-tubercular agents: Their DNA cleavage ability and BSA interaction study.

Eur J Med Chem 2018 Apr 20;150:864-875. Epub 2018 Mar 20.

Centre for Nano and Material Sciences, Jain University, Jain Global Campus, Jakkasandra Post, Bangalore, 562112, India. Electronic address:

As a contribution to the development of novel coumarin-oxime ether conjugates with therapeutically interesting properties, a series of coumarin-oxime ether (1a-1j) was synthesised using S2 reaction of bromomethyl coumarins with butane-2,3-dione monoxime. Invitro anti-tuberculosis activityagainstMTBHRv strain was established for the coumarin-oxime ether (1a-1j). Most of the compounds exhibited significant activity with minimum inhibitory concentration (MIC)in the range of 0. Read More

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http://dx.doi.org/10.1016/j.ejmech.2018.03.042DOI Listing
April 2018
17 Reads
3.450 Impact Factor

Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study.

BMC Med 2018 03 28;16(1):46. Epub 2018 Mar 28.

University of St Andrews Medical School, St Andrews, UK.

Background: Drug-induced liver injury (DILI) is a common complication of tuberculosis treatment. We utilised data from the REMoxTB clinical trial to describe the incidence of predisposing factors and the natural history in patients with liver enzyme levels elevated in response to tuberculosis treatment.

Methods: Patients received either standard tuberculosis treatment (2EHRZ/4HR), or a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Read More

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http://dx.doi.org/10.1186/s12916-018-1033-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875008PMC
March 2018
11 Reads

Investigating the CYP2E1 Potential Role in the Mechanisms Behind INH/LPS-Induced Hepatotoxicity.

Front Pharmacol 2018 7;9:198. Epub 2018 Mar 7.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.

Tuberculosis (TB) is one of the oldest infectious diseases that affected humankind and remains one of the world's deadliest communicable diseases that could be considered as global emergency, but the discovery and development of isoniazid (INH) in the 1950s paved the way to an effective single and/or combined first-line anti-TB therapy. However, administration of INH induces severe hepatic toxicity in some patients. Previously, we establish a rat model of INH hepatotoxicity utilizing the inflammatory stress theory, in which bacterial lipopolysaccharide (LPS) potentially enhanced INH toxicity. Read More

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http://dx.doi.org/10.3389/fphar.2018.00198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850051PMC
March 2018
5 Reads

Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation.

NPJ Syst Biol Appl 2018 26;4:10. Epub 2018 Feb 26.

Institute of Applied Microbiology-iAMB, Aachen Biology and Biotechnology-ABBt, RWTH Aachen University, 52074 Aachen, Germany.

Drug-induced perturbations of the endogenous metabolic network are a potential root cause of cellular toxicity. A mechanistic understanding of such unwanted side effects during drug therapy is therefore vital for patient safety. The comprehensive assessment of such drug-induced injuries requires the simultaneous consideration of both drug exposure at the whole-body and resulting biochemical responses at the cellular level. Read More

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http://dx.doi.org/10.1038/s41540-018-0048-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827733PMC
February 2018
8 Reads

Isoniazid induces apoptosis: Role of oxidative stress and inhibition of nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2).

Life Sci 2018 Apr 27;199:23-33. Epub 2018 Feb 27.

PCS 103 Genotoxicity Lab, Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address:

Aims: Long-term treatment of Isoniazid (INH) in tuberculosis (TB) patients can lead to anti-tuberculosis drug-induced hepatotoxicity. To understand the mechanism of hepatotoxicity, an attempt has been made to elucidate the role of Nrf2, a transcription factor induced by oxidative stress, in INH induced apoptosis liver cancer cell lines.

Materials And Methods: Cytotoxicity was evaluated by MTT assay. Read More

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http://dx.doi.org/10.1016/j.lfs.2018.02.037DOI Listing
April 2018
8 Reads
2.702 Impact Factor

New hydrazides derivatives of isoniazid against Mycobacterium tuberculosis: Higher potency and lower hepatocytotoxicity.

Eur J Med Chem 2018 Feb 31;146:529-540. Epub 2018 Jan 31.

Fundacao Oswaldo Cruz, Instituto de Tecnologia em Fármacos, Farmanguinhos-Fiocruz, Departamento de Sintese Farmacos, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil. Electronic address:

Tuberculosis (TB) is one of the leading causes of death worldwide. The emergence of multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) and TB-HIV co-infection are major public health challenges. The anti-TB drugs of first choice were developed more than 4 decades ago and present several adverse effects, making the treatment of TB even more complicated and the development of new chemotherapeutics for this disease imperative. Read More

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http://dx.doi.org/10.1016/j.ejmech.2018.01.071DOI Listing
February 2018
10 Reads

[An unintended diagnosis: Serotonergic toxicity secondary to drug interactions. Case reports].

Arch Argent Pediatr 2018 Feb;116(1):e115-e120

Unidad de Toxicología, Hospital de Niños "Ricardo Gutiérrez", Ciudad Autónoma de Buenos Aires.

Serotonin toxicity is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, intentional self-poisoning and inadvertent interactions (SSRI-isoniazid). Although this pathology is increasingly common, it is not well recognized by physicians and manifestations may be wrongly attributed to another cause. Read More

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http://dx.doi.org/10.5546/aap.2018.e115DOI Listing
February 2018
2 Reads

Protective effects of salep against isoniazid liver toxicity in wistar rats.

J Tradit Complement Med 2018 Jan 21;8(1):239-243. Epub 2017 Jun 21.

Zoonoses Research Center, Jahrom University of Medical Sciences, Jahrom, Iran.

Introduction: Isoniazid is a drug for treatment of tuberculosis. One of the main side effects of this drug is hepatotoxicity, which is a major cause of treatment interruption in tuberculosis. This study is about the preventive effect of Salep on this side effect of isoniazid. Read More

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http://dx.doi.org/10.1016/j.jtcme.2017.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756020PMC
January 2018
5 Reads

Isoniazid Preventive Therapy for People With HIV Who Are Heavy Alcohol Drinkers in High TB-/HIV-Burden Countries: A Risk-Benefit Analysis.

J Acquir Immune Defic Syndr 2018 Apr;77(4):405-412

Section of Infectious Diseases, Boston Medical Center, Boston, MA.

Background: Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV) and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in 3 high TB-/HIV-burden countries. Read More

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http://dx.doi.org/10.1097/QAI.0000000000001610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825241PMC
April 2018
13 Reads

Mannose-functionalized solid lipid nanoparticles are effective in targeting alveolar macrophages.

Eur J Pharm Sci 2018 Mar 8;114:103-113. Epub 2017 Dec 8.

CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal.

Mannose receptor is highly expressed on alveolar macrophages, being a potential target to promote the specific local drug delivery of anti-tuberculosis agents through the use of functionalized nanocarriers. In this work, isoniazid (Isn)-loaded solid lipid nanoparticles (SLN), reinforced with stearylamine (SA) were produced by double emulsion technique and further surface-functionalized with mannose in a straightforward chemical approach. Upon pre-formulation assessment, SLN close to 500 nm average size, positively charged and with association efficiency of ISN close to 50% were obtained. Read More

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http://dx.doi.org/10.1016/j.ejps.2017.12.006DOI Listing
March 2018
29 Reads

Pharmacokinetics and pharmacogenetics of anti-tubercular drugs: a tool for treatment optimization?

Expert Opin Drug Metab Toxicol 2018 Jan 18;14(1):59-82. Epub 2017 Dec 18.

a Unit of Infectious Diseases, Department of Medical Sciences , University of Torino , Torino , Italy.

Introduction: WHO global strategy is to end tuberculosis epidemic by 2035. Pharmacokinetic and pharmacogenetic studies are increasingly performed and might confirm their potential role in optimizing treatment outcome in specific settings and populations. Insufficient drug exposure seems to be a relevant factor in tuberculosis outcome and for the risk of phenotypic resistance. Read More

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http://dx.doi.org/10.1080/17425255.2018.1416093DOI Listing
January 2018
6 Reads

Synthesis and In Vitro Antimycobacterial Activity of Novel N-Arylpiperazines Containing an Ethane-1,2-diyl Connecting Chain.

Molecules 2017 Nov 30;22(12). Epub 2017 Nov 30.

Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork T12 P928, UK.

Novel 1-(2-{3-/4-[(alkoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)-piperazin-1-ium chlorides (alkoxy = methoxy to butoxy; -) have been designed and synthesized through multistep reactions as a part of on-going research programme focused on finding new antimycobacterials. Lipophilic properties of these compounds were estimated by RP-HPLC using methanol/water mobile phases with a various volume fraction of the organic modifier. The log values, which were extrapolated from intercepts of a linear relationship between the logarithm of a retention factor (log ) and volume fraction of a mobile phase modifier (), varied from 2. Read More

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http://dx.doi.org/10.3390/molecules22122100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6149664PMC
November 2017
12 Reads

Cytotoxic and acute toxicity studies of isoniazid derivatives.

Pak J Pharm Sci 2017 Nov;30(6(Supplementary)):2411-2415

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, USA.

Cancer is ultimately the result of cells that hysterically grow and do not die. Cells can experience uncontrolled growth if there are mutations to DNA, and therefore, alterations to the genes involved in cell division. Cancer occurs when a cell's gene mutations make the cell unable to correct DNA damage and is unable to destroy itself. Read More

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November 2017
6 Reads

Association between effectiveness of tuberculosis treatment and cytochrome P-4502E1 polymorphism of the patients.

Int J Mycobacteriol 2017 Oct-Dec;6(4):396-400

Department of Internal Medicine, Kharkiv National Medical University; Department of Internal Medicine, V. N. Karazin Kharkiv National University, Kharkiv, Ukraine.

Context: The risk of antituberculosis (TB) drug-induced liver injury could be determined by patients' genotype polymorphism of the xenobiotic-metabolizing enzymes. To find the meaning of cytochrome P-4502E1 (CYP2E1) polymorphism in TB patients. Corresponding of CYP2E1 polymorphism in TB patients with the level of isoniazid and rifampicin as well as for the outcome and toxicity development during inpatient TB treatment. Read More

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http://dx.doi.org/10.4103/ijmy.ijmy_168_17DOI Listing
September 2018
5 Reads

Modulation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation by ursolic acid (UA) attenuates rifampin-isoniazid cytotoxicity.

Phytomedicine 2017 Dec 25;36:37-49. Epub 2017 Sep 25.

Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan; Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address:

Background: Interactions between transcriptional inducers of cytochrome P450 (CYP450) enzymes and therapeutic drugs may be prevented by antagonizing the activation of a nuclear receptor (NR), pregnane X receptor (PXR, NR1I2), thus improving therapeutic efficacy.

Purpose: In the present study, we aim to identify that ursolic acid (UA), a widely distributed pentacyclic triterpene, may act as an effective antagonist of PXR and its sister NR receptor, constitutive androstane receptor (CAR, NR1I3).

Methods: The hepatocellular carcinoma cell line, HepG2, was used to evaluate the promoter activity of PXR and CAR target genes, CYP3A4 and CYP2B6, respectively. Read More

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http://dx.doi.org/10.1016/j.phymed.2017.09.016DOI Listing
December 2017
17 Reads
3.130 Impact Factor

Assessment of hepatotoxicity of first-line anti-tuberculosis drugs on Wistar rats.

Naunyn Schmiedebergs Arch Pharmacol 2018 01 9;391(1):83-93. Epub 2017 Nov 9.

Cytogenetics Laboratory, Department of Zoology, Panjab University, Chandigarh, 160014, India.

Adverse drug reactions are inevitable risk factors associated with use of modern medicines. First-line anti-tuberculosis drugs contribute to diverse pathological complications, and hepatotoxicity is one of them. This study investigated the effects of anti-TB drugs in combination (rifampicin [RIF] + isoniazid [INH] + pyrazinamide [PZA]) on Wistar rats. Read More

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http://dx.doi.org/10.1007/s00210-017-1434-8DOI Listing
January 2018
12 Reads

Impairment of Mitochondrial Biogenesis and Dynamics Involved in Isoniazid-Induced Apoptosis of HepG2 Cells Was Alleviated by p38 MAPK Pathway.

Front Pharmacol 2017 26;8:753. Epub 2017 Oct 26.

Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, PLA, Beijing, China.

Isoniazid (INH), a widely used first-line antitubercular drug, has been noted to be associated with hepatotoxicity. In spite of extensive researches over many decades, the mechanism of INH-induced hepatotoxicity still remains poorly understood. Recently, mitochondrial toxicity has been emerging as a new paradigm for INH-induced hepatotoxicity. Read More

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http://dx.doi.org/10.3389/fphar.2017.00753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662931PMC
October 2017
20 Reads

Systematic Review of Salivary Versus Blood Concentrations of Antituberculosis Drugs and Their Potential for Salivary Therapeutic Drug Monitoring.

Ther Drug Monit 2018 02;40(1):17-37

University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands.

Background: Therapeutic drug monitoring is useful in the treatment of tuberculosis to assure adequate exposure, minimize antibiotic resistance, and reduce toxicity. Salivary therapeutic drug monitoring could reduce the risks, burden, and costs of blood-based therapeutic drug monitoring. This systematic review compared human pharmacokinetics of antituberculosis drugs in saliva and blood to determine if salivary therapeutic drug monitoring could be a promising alternative. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345279PMC
February 2018
21 Reads

First-line antituberculosis drugs disrupt endocrine balance and induce ovarian and uterine oxidative stress in rats.

J Basic Clin Physiol Pharmacol 2018 Mar;29(2):131-140

Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria, Phone: +234-81-6304-7157, E-mail:

Background: The first-line antituberculosis (anti-TB) drugs, isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PZA), are effective in the treatment of pulmonary tuberculosis. However, the toxicity of these drugs in the clinical setting limits their use. Here, we evaluated the effects of anti-TB drugs on the reproductive system in female rats. Read More

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http://dx.doi.org/10.1515/jbcpp-2017-0087DOI Listing
March 2018
16 Reads

Cytochrome P450 1A1 and 1B1 promoter CpG island methylation regulates rat liver injury induced by isoniazid.

Mol Med Rep 2018 Jan 31;17(1):753-762. Epub 2017 Oct 31.

Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063200, P.R. China.

DNA methylation is an important component of epigenetics that is involved in the occurrence and development of a variety of diseases. The present study aimed to clarify the relationship between cytochrome P450 (CYP)1A1 and CYP1B1 promoter CpG island methylation and isoniazid‑induced liver injury in rats, and to explore the possible mechanism, rats were given an intragastric dose of isoniazid (55 mg·kg‑1·d‑1). High performance liquid chromatography was used to analyze the DNA methylation level of the whole genome in liver tissue. Read More

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http://dx.doi.org/10.3892/mmr.2017.7929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780152PMC
January 2018
19 Reads

Synthesis and biological evolution of hydrazones derived from 4-(trifluoromethyl)benzohydrazide.

Bioorg Med Chem Lett 2017 12 21;27(23):5185-5189. Epub 2017 Oct 21.

Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.

Reflecting the known biological activity of isoniazid-based hydrazones, seventeen hydrazones of 4-(trifluoromethyl)benzohydrazide as their bioisosters were synthesized from various benzaldehydes and aliphatic ketones. The compounds were screened for their in vitro activity against Mycobacterium tuberculosis, nontuberculous mycobacteria (M. avium, M. Read More

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http://dx.doi.org/10.1016/j.bmcl.2017.10.050DOI Listing
December 2017
10 Reads

Pharmacokinetic studies of a three-component complex that repurposes the front line antibiotic isoniazid against Mycobacterium tuberculosis.

Tuberculosis (Edinb) 2017 12 4;107:149-155. Epub 2017 Sep 4.

NMR Lab, Chemistry Department, Texas A&M University, College Station, TX, USA.

The frontline tuberculosis (Tb) antibiotic isoniazid has been repurposed using a three component complex aimed at increasing the delivery efficiency and adding new avenues to its mechanism of action. This study focuses on pharmacokinetic studies of the isoniazid-sucrose-copper (II)-PEG-3350 complex. The assays include the Plasma Protein Binding Assay (85. Read More

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http://dx.doi.org/10.1016/j.tube.2017.08.011DOI Listing
December 2017
9 Reads