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J Bras Nefrol 2021 Apr 9. Epub 2021 Apr 9.

Instituto de Cardiologia do Distrito Federal, Brasília, DF, Brasil.

Introduction: Tuberculosis (TB) is a possible serious complication of solid organ transplantation, associated with high mortality and morbidity. Post-transplant TB has varied pathogenesis with many approaches to its prevention, which is the most important way to reduce its incidence. Treatment of TB in organ recipients is challenging because of drug toxicity and interaction with immunosuppressants. Read More

Toxicology 2021 05 23;455:152749. Epub 2021 Mar 23.

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi Province, 712100, PR China. Electronic address:

Isoniazid (INH), a synthetic first-line tuberculosis antibiotic, has been widely used in clinical treatment. It has been reported to cause toxic effects at multiple tissue sites and also increases the incidence of adverse pregnancy outcomes; but the mechanism of action of INH on the reproductive system of female mammals remains unclear. Here, we demonstrate that oral INH (40 mg/kg/day every other day for 28 days) severely affects oocyte maturation and fertilization, late blastocyst development and fertility. Read More

Clin Toxicol (Phila) 2021 Jun 23;59(6):451-456. Epub 2021 Mar 23.

New Mexico Poison and Drug Information Center, Albuquerque, NM, USA.

Background: Seizures are a common manifestation of toxic exposures requiring immediate and possibly ongoing management. Guidelines recommend benzodiazepines as first-line therapy for toxic seizures; however, there is a paucity of literature regarding optimal secondary treatment. We systematically evaluated the available literature for second-line treatment of toxic seizures. Read More

Hum Exp Toxicol 2021 Mar 17:960327121997975. Epub 2021 Mar 17.

Department of Biochemistry, 29751Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Drug induced liver toxicity is a serious health complication leading to high mortality rates and post marketing withdrawal of drugs. Although considered to be the gold standard biomarkers; aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase have been found to have specificities beyond liver, therefore more specific and predictive markers for the detection of antitubercular drug mediated liver damage are required. Unfortunately, the effectiveness of currently used first line antitubercular drugs namely isoniazid, rifampicin, pyrazinamide is often accompanied with liver injury, impeding the cure of patients. Read More

Pharmacotherapy 2021 Mar 4. Epub 2021 Mar 4.

Research Center, CIUSSS du Nord-de-l'île-de-Montréal, University of Montreal, Montreal, Quebec, Canada.

Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. Read More

Front Microbiol 2020 26;11:634640. Epub 2021 Jan 26.

Division of Bioinformatics and Biochemistry, Department of Materials, Environmental Sciences and Urban Planning, Polytechnic University of Marche, Ancona, Italy.

Given the upsurge of drug-resistant tuberculosis worldwide, there is much focus on developing novel drug combinations allowing shorter treatment duration and a lower toxicity profile. Nicotinamide adenine dinucleotide (NAD) biosynthesis targeting is acknowledged as a promising strategy to combat drug-susceptible, drug-resistant, and latent tuberculosis (TB) infections. In this review, we describe the potential synergy of NAD biosynthesis inhibitors with several TB-drugs in prospective novel combination therapy. Read More

Eur J Pharm Biopharm 2021 Mar 24;160:82-91. Epub 2021 Jan 24.

University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. Electronic address:

Solid lipid nanoparticles (SLNs) are presently being promoted to improve bioavailability of encapsulated drugs. These are well tolerated in living systems, as they are made from biocompatible material. Despite finding extensive applicability, these systems have not been sufficiently investigated for the toxicity so far. Read More

Niger Med J 2020 Sep-Oct;61(5):281-283. Epub 2020 Oct 13.

Department of Paediatrics, Paediatric Pulmonology Unit, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria.

The emergence of resistant strains of mycobacterium tuberculosis (TB) to antituberculous drugs has compounded the management of the chronic infection. More than 90% of rifampicin (RIF)-resistant isolates are also isoniazid resistant; hence, rifampicin resistance (RR) is a surrogate marker for multidrug resistant TB (MDR-TB). Although there are limited reports of pediatric RR/MDR-TB in Nigeria, there had not been similar report in our hospital until now. Read More

Int J Infect Dis 2021 Mar 19;104:562-567. Epub 2021 Jan 19.

Service de Pharmacologie Clinique, CHU Monastir/ Faculté de Médecine, Université de Monastir, Tunisia.

Aims: To develop a pharmacokinetic model of isoniazid (INH) concentration taking into account demographic factors and genetic variables [N-acetyltransferase 2 (NAT2) genotype], and to propose an initial INH dosage that could maximize the probability of achieving the desired INH concentration.

Methods: A retrospective analysis was undertaken of INH concentration data collected from patients with tuberculosis in Tunisia.

Results: In total, 118 patients were included in this study. Read More

Infection 2021 Feb 23;49(1):29-56. Epub 2020 Dec 23.

Christian-Albrechts-University of Kiel, Institue for Infection Medicine, Brunswiker Str. 4, D-24105, Kiel, Germany.

Background: Selective toxicity antibacteribiotics is considered to be due to interactions with targets either being unique to bacteria or being characterized by a dichotomy between pro- and eukaryotic pathways with high affinities of agents to bacterial- rather than eukaryotic targets. However, the theory of selective toxicity oversimplifies the complex modes of action of antibiotics in pro- and eukaryotes.

Methods And Objective: This review summarizes data describing multiple modes of action of antibiotics in eukaryotes. Read More

J Clin Tuberc Other Mycobact Dis 2021 Feb 16;22:100201. Epub 2020 Nov 16.

U.S. Centers for Disease Control and Prevention, Division of TB Elimination, Atlanta, GA, United States.

Background: In 2019, the World Health Organization released guidelines reflecting major changes in multidrug-resistant tuberculosis (MDR-TB) management-prioritizing fluoroquinolones, bedaquiline, and linezolid (LZD) while de-emphasizing previously favored injectable agents. In some cases, linezolid use is associated with gastrointestinal intolerance, mitochondrial toxicity, and significant drug interactions. CDC's Division of Tuberculosis Elimination supports a network of regional TB Centers of Excellence, which provide medical consultation to healthcare providers. Read More

Future Med Chem 2021 Feb 9;13(3):251-267. Epub 2020 Dec 9.

Department of Microbiology & Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 31151, South Korea.

Tuberculosis is the leading cause of mortality among infectious diseases worldwide. Finding a new competent anti tubercular therapy is essential. We screened thousands of compounds and evaluated their efficacy against . Read More

Front Cell Infect Microbiol 2020 13;10:582416. Epub 2020 Nov 13.

SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit & DST/NRF Centre of Excellence for Biomedical TB Research, Institute of Infectious Disease and Molecular Medicine & Department of Pathology, University of Cape Town, Cape Town, South Africa.

Compounds with novel modes of action are urgently needed to develop effective combination therapies for the treatment of tuberculosis. In this study, a series of compounds was evaluated for activity against replicating and Vero cell line toxicity. Fourteen of the compounds with activities in the low micrometer range and a favorable selectivity index were classified using reporter strains of which showed that six interfered with cell wall metabolism and one disrupted DNA metabolism. Read More

Chemosphere 2021 Feb 28;265:129109. Epub 2020 Nov 28.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, Shandong Province, PR China. Electronic address:

Aims: This study evaluated the neurodevelopmental toxicity of isoniazid (INH) in zebrafish embryos and the underlying mechanism.

Methods: Zebrafish embryos were exposed to different concentrations (2 mM, 4 mM, 8 mM, 16 mM, 32 mM) INH for 120 hpf. During the exposure period, the percentage of embryo/larva mortality, hatching, and morphological malformation were checked every 24 h until 120 hpf. Read More

Antimicrob Agents Chemother 2020 12 16;65(1). Epub 2020 Dec 16.

Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

Optimal dosing of children with tuberculous meningitis (TBM) remains uncertain and is currently based on the treatment of pulmonary tuberculosis in adults. This study aimed to investigate the population pharmacokinetics of isoniazid, rifampin, pyrazinamide, and ethambutol in Vietnamese children with TBM, to propose optimal dosing in these patients, and to determine the relationship between drug exposure and treatment outcome. A total of 100 Vietnamese children with TBM were treated with an 8-month antituberculosis regimen. Read More

Curr Top Med Chem 2021 ;21(4):295-306

Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa.

Background: Tuberculosis remains one of the most deadly infectious diseases worldwide due to the emergence of multi-drug resistance (MDR) and extensively drug resistance (XDR) strains of Mycobacterium tuberculosis (MTB).

Aims: Currently, available drugs are getting resistant and toxic. Hence, there is an urgent need for the development of potent molecules to treat tuberculosis. Read More

Antimicrob Agents Chemother 2020 12 16;65(1). Epub 2020 Dec 16.

Mycobacterium Research Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India

Isoniazid (INH), one of the first-line drugs used for the treatment of tuberculosis, is a prodrug which is activated by the intracellular KatG enzyme of The activated drug hinders cell wall biosynthesis by inhibiting the InhA protein. INH-resistant strains of usually have mutations in , , , , and genes. However, INH-resistant strains which do not have mutations in any of these genes are reported, suggesting that these strains may adopt some other mechanism to become resistant to INH. Read More

Indian J Radiol Imaging 2020 Apr-Jun;30(2):218-221. Epub 2020 Jul 13.

Senior Consultant Radiologist and HOD, Consultant Radiologist, Consultant Radiologist, Department of Radiology and Imaging Sciences, Meenakshi Hospital, Tanjore, Tamil Nadu, India.

Dentate nucleus, the largest deep nucleus of the cerebellum, is affected by numerous conditions, including leukodystrophies, toxins, drugs, infections, and various metabolic and inflammatory conditions. This case report is a drug-induced cerebellitis, caused by isoniazid (INH), characterized in magnetic resonance imaging (MRI) as bilateral dentate nuclei hyperintensity. Isoniazid, an antituberculosis therapy (ATT) drug, is both neurotoxic and hepatotoxic but cerebellitis is a rare complication. Read More

J Mater Chem B 2020 12 16;8(45):10353-10359. Epub 2020 Oct 16.

School of Chemical Engineering, Sichuan University, Chengdu 610065, P. R. China.

Hydrazine is a well-known genotoxic impurity which may be present in some important drugs, such as isoniazid and hydralazine. It may be ingested along with the drug or generated as a metabolite in the human body. Hence, monitoring the level of hydrazine in the human body is of great importance. Read More

Pharmaceutics 2020 Oct 10;12(10). Epub 2020 Oct 10.

LAQV, REQUIMTE, Departamento de Química da Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.

Tuberculosis is one of the ten causes of morbidity and mortality worldwide caused by complex. Some of the anti-tuberculosis drugs used in clinic studies, despite being effective for the treatment of tuberculosis, present serious adverse effects as well as poor bioavailability, stability, and drug-resistance problems. Thus, it is important to develop approaches that could provide shorter drug regimens, preventing drug resistance, toxicity of the antibiotics, and improve their bioavailability. Read More

Clin Ther 2020 11 5;42(11):e220-e241. Epub 2020 Oct 5.

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA. Electronic address:

Purpose: This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis (TB), evaluates whether the current INH dose regimen is appropriate in patients with TB, and evaluates the impact of N-acetyl-transferase-2 (NAT2) status on the PK properties of INH.

Methods: A systematic approach was conducted to find studies with relevant INH PK data published in the English language up to February 2018. The PK properties of INH were extracted with their respective INH dosages and were dose normalized to allow a fair comparison between healthy volunteers and patients with TB. Read More

Pak J Pharm Sci 2020 Mar;33(2(Supplementary)):805-814

Punjab University College of Pharmacy, University of Punjab, Lahore, Pakistan.

Rosa brunonii L., a less investigated plant contains flavonoid glycosides and is used to treat stomach ailments, heart problems, and diabetes in folk. The crude extract of the plant possesses antioxidant activity. Read More

Indian J Tuberc 2020 Jul 20;67(3):407-410. Epub 2020 Jan 20.

Department of Medicine, LTM Medical College & LTM General Hospital, Mumbai, India.

Isoniazid is an essential drug in the management of tuberculosis but there is a high degree of variation in the Indian population's capacity to acetylate or inactivate isoniazid to the inactive metabolite acetyl isoniazid, and they can be distinctly characterized phenotypically as being either slow or rapid inactivators (the concentration of the enzyme being higher in rapid inactivators). Several mutations in the N-acetyl transference 2 (NAT2) gene account for majority of the slow acetylator genotypes in the human population (NAT2*5A, NAT2*5B, and NAT2*6A). Such individuals are at a greater risk of drug-induced adverse reactions due to reduced drug elimination, compared to those possessing the wild type allele. Read More

Behav Pharmacol 2020 12;31(8):738-747

Department of Chemistry, Pontifical Catholic University of Rio de Janeiro.

Converging evidence indicates that neurotoxicity and memory impairment in Alzheimer's disease is induced by brain accumulation of soluble amyloid-β oligomers (AβOs). Physiological metals are poorly distributed and concentrated in the senile plaques typical of Alzheimer's disease, where they may be coordinated to the amyloid-β peptide (Aβ). Indeed, zinc and copper increase Aβ oligomerization and toxicity. Read More

Bioorg Med Chem Lett 2020 10 24;30(19):127434. Epub 2020 Jul 24.

Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University SubCampus, Osmanabad 413501, MS, India. Electronic address:

In the present study, a series of new isoniazid embedded triazole derivatives have been synthesized. These compounds were evaluated for their in vitro antitubercular and antimicrobial activities. Among the screened compounds, six have exhibited potent antitubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC value 0. Read More

Drug Chem Toxicol 2020 Jul 26:1-5. Epub 2020 Jul 26.

Faculty of Medicine and Pharmacy, Laboratory of Chemistry-Biochemistry, Environment, Nutrition, and Health, Hassan II University, Casablanca, Morocco.

Drug-induced hepatotoxicity is one of the most challenging hepatic diseases faced nowadays due to a large number of drugs currently used in clinical practice, the enormous dietary supplements which are potentially hepatotoxic, as well as the ability to appear with different clinical symptoms and the absence of specific markers. The current research survey was conducted to investigate drug-induced hepatotoxicity and demographic characteristics of patients with liver damage in the general Maghrebian population between 1992 and 2018. To achieve this goal a questionnaire was adopted to report details on the undesirable effects of drugs and demographic characteristics of affected patients. Read More

Toxicol Appl Pharmacol 2020 09 14;402:115134. Epub 2020 Jul 14.

Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, China,. Electronic address:

Isoniazid (INH)-induced liver injury may be associated with inhibition of the liver farnesoid X receptor (FXR). However, the relationship between FXR and INH-induced liver injury remained unclear. The present study was performed to clarify the role of inhibition of FXR in the pathogenesis of INH-induced liver injury and to further identify potential inhibitors of FXR from INH and its metabolites. Read More

Eur J Immunol 2020 12 29;50(12):1976-1987. Epub 2020 Jul 29.

Immunology Division, CSIR-Institute of Microbial Technology, Chandigarh, India.

Tuberculosis (TB) continues to remain a global threat due to the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains and toxicity associated with TB drugs. Intestinal microbiota has been reported to affect the host response to immunotherapy and drugs. However, how it affects the potency of first-line TB drug isoniazid (INH) is largely unknown. Read More

Cells 2020 07 9;9(7). Epub 2020 Jul 9.

Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Tuberculosis is a global health threat that affects millions of people every year, and treatment-limiting toxicity remains a considerable source of treatment failure. Recent reports have characterized the nature of -mediated hepatotoxicity and the systemic toxicity of antitubercular drugs. The antitubercular drug isoniazid plays a role in such pathologic states as acute intermittent porphyria, anemia, hepatotoxicity, hypercoagulable states (deep vein thrombosis, pulmonary embolism, or ischemic stroke), pellagra (vitamin B deficiency), peripheral neuropathy, and vitamin B deficiency. Read More

Carbohydr Res 2020 Sep 27;495:108070. Epub 2020 Jun 27.

School of Chemical Sciences, Central University of Gujarat, Gandhinagar, 382030, India. Electronic address:

Nanoparticles-based drug delivery is at the forefront in the field of pharmaceutical and medicinal research to eradicate or alleviate the associated impediments, such as prolonged treatment time, high doses, toxicity and resistance problem of anti-tuberculosis drugs for the treatment of age-old tuberculosis disease. Herein, the first-line anti-tuberculosis drugs were loaded into the biodegradable starch nanocrystals and native starch to improve the therapeutic profile addressing the existing issues related to conventional drugs. The loading performance of anti-tuberculosis drugs with starch nanocrystals and native starch was found in the range of 65-95%. Read More