Publications by authors named "Saleh A Bahashwan"

12 Publications

  • Page 1 of 1

Pharmacological activities of some triazinopyrazolothieno pyrimidine derivatives.

Acta Pharm 2017 Sep;67(3):407-414

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Triazinopyrazolothieno pyrimidine derivatives 1-5 were evaluated for their anti-inflammatory, analgesic and anticancer activities and acute toxicity. Anti-inflammatory activity of the compounds was studied using the carrageenan test. All tested compounds showed analgesic activity, 3-methoxycarbonyl-4,6-dimethyl-8-[(N-methylindolyl)methyl] pyrimido [5',4':4,5]thieno [3',2'-3,4]pyrazolo [5,1-c]triazine (4) showed activity comparable to that of diclofenac. Compounds 1-5 were also screened for anticancer activity on a human lung cancer cell line (A549) and a human prostate cancer cell line (DU145) using the MTT micro-cultured tetrazolium assay method. Compound 4 showed also significant anticancer activity against both cancer cell lines, comparable to that of doxorubicin. The most active compounds were tested for their acute toxicity and median lethal doses were evaluated.
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http://dx.doi.org/10.1515/acph-2017-0022DOI Listing
September 2017

Knowledge, awareness, and attitudes toward antibiotic use and antimicrobial resistance among Saudi population.

Int J Clin Pharm 2016 Oct 29;38(5):1261-8. Epub 2016 Aug 29.

Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Charles University, 50005, Prague, Hradec Kralove, Czech Republic.

Background Inappropriate use of antibiotics is a public health problem of great concern. Objective To evaluate knowledge of antibiotics, race, gender and age as independent risk factors for self-medication. Setting Residents and population from different regions of Saudi Arabia. Methods We conducted a cross sectional survey study among residents. Data were collected between June 2014 to May, 2015 from 1310 participants and data were recorded anonymously. The questionnaire was randomly distributed by interview of participants and included sociodemographic characteristics, antibiotics knowledge, attitudes and behavior with respect to antibiotics usage. Main outcome measure Population aggregate scores on questions and data were analyzed using univariate logistic regression to evaluate the influence of variables on self-prescription of antibiotics. Results The response rate was 87.7 %. A cumulative 63.6 % of participants reported to have purchased antibiotics without a prescription from pharmacies; 71.1 % reported that they did not finish the antibiotic course as they felt better. The availability of antibiotics without prescription was found to be positively associated with self-medication (OR 0.238, 95 % CI 0.17-0.33). Of those who used prescribed or non-prescribed antibiotics, 44.7 % reported that they kept left-over antibiotics from the incomplete course of treatment for future need. Interestingly, 62 % of respondents who used drugs without prescription agreed with the statement that antibiotics should be access-controlled prescribed by a physician. We also found significant association between storage, knowledge/attitudes and education. Conclusions The overall level of awareness on antibiotics use among residents in Saudi Arabia is low. This mandates public health awareness intervention programs to be implemented on the use of antibiotics.
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http://dx.doi.org/10.1007/s11096-016-0362-xDOI Listing
October 2016

Airway oxidative stress causes vascular and hepatic inflammation via upregulation of IL-17A in a murine model of allergic asthma.

Int Immunopharmacol 2016 May 5;34:173-182. Epub 2016 Mar 5.

Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Oxidants are generated in asthmatic airways due to infiltration of inflammatory leukocytes and resident cells in the lung. Reactive oxygen species (ROS) such as hydrogen peroxide and superoxide radical may leak into systemic circulation when generated in uncontrolled manner and may impact vasculature. Our previous studies have shown an association between airway inflammation and systemic inflammation; however so far none has investigated the impact of airway oxidative inflammation on hepatic oxidative stress and Th1/Th2/Th17 cytokine markers in liver/vasculature in a murine model of asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of systemic/hepatic Th1/Th2/Th17 cytokines balance and hepatic oxidative stress. Mice were sensitized intraperitoneally with cockroach extract (CE) in the presence of aluminum hydroxide followed by several intranasal (i.n.) challenges with CE. Mice were then assessed for systemic/hepatic inflammation through assessment of Th1/Th2/Th17 cytokines and oxidative stress (iNOS, protein nitrotyrosine, lipid peroxides and myeloperoxidase activity). Challenge with CE led to increased Th2/Th17 cytokines in blood/liver and hepatic oxidative stress. However, only Th17 related pro-inflammatory markers were upregulated by hydrogen peroxide (H2O2) inhalation in vasculature and liver, whereas antioxidant treatment, N-acetyl cysteine (NAC) downregulated them. Hepatic oxidative stress was also upregulated by H2O2 inhalation, whereas NAC attenuated it. Therefore, our study shows that airway oxidative inflammation may contribute to systemic inflammation through upregulation of Th17 immune responses in blood/liver and hepatic oxidative stress. This might predispose these patients to increased risk for the development of cardiovascular disorders.
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http://dx.doi.org/10.1016/j.intimp.2016.03.003DOI Listing
May 2016

Oxidative airway inflammation leads to systemic and vascular oxidative stress in a murine model of allergic asthma.

Int Immunopharmacol 2015 May 3;26(1):237-45. Epub 2015 Apr 3.

Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina, Saudi Arabia.

Oxidant-antioxidant imbalance plays an important role in repeated cycles of airway inflammation observed in asthma. It is when reactive oxygen species (ROS) overwhelm antioxidant defenses that a severe inflammatory state becomes apparent and may impact vasculature. Several studies have shown an association between airway inflammation and cardiovascular complications; however so far none has investigated the link between airway oxidative stress and systemic/vascular oxidative stress in a murine model of asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of vascular/systemic oxidant-antioxidant balance. Rats were sensitized intraperitoneally with ovalbumin (OVA) in the presence of aluminum hydroxide followed by several intranasal (i.n.) challenges with OVA. Rats were then assessed for airway and vascular inflammation, oxidative stress (ROS, lipid peroxides) and antioxidants measured as total antioxidant capacity (TAC) and thiol content. Challenge with OVA led to increased airway inflammation and oxidative stress with a concomitant increase in vascular inflammation and oxidative stress. Oxidative stress in the vasculature was significantly inhibited by antioxidant treatment, N-acetyl cysteine; whereas hydrogen peroxide (H2O2) inhalation worsened it. Therefore, our study shows that oxidative airway inflammation is associated with vascular/systemic oxidative stress which might predispose these patients to increased cardiovascular risk.
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http://dx.doi.org/10.1016/j.intimp.2015.03.032DOI Listing
May 2015

Androgen receptor antagonists and anti-prostate cancer activities of some newly synthesized substituted fused pyrazolo-, triazolo- and thiazolo-pyrimidine derivatives.

Int J Mol Sci 2014 Nov 24;15(11):21587-602. Epub 2014 Nov 24.

Pharmacology and Toxicology Department, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

A series of substituted pyrazole, triazole and thiazole derivatives (2-13) were synthesized from 1-(naphtho[1,2-d]thiazol-2-yl)hydrazine as starting material and evaluated as androgen receptor antagonists and anti-prostate cancer agents. The newly synthesized compounds showed potent androgen receptor antagonists and anti-prostate cancer activities with low toxicity (lethal dose 50 (LD50)) comparable to Bicalutamide as reference drug. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, and MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, LD50 values and pharmacological activities of the synthesized compounds are reported.
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http://dx.doi.org/10.3390/ijms151121587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264242PMC
November 2014

Modulatory effects of meloxicam on cardiotoxicity and antitumor activity of doxorubicin in mice.

Cancer Chemother Pharmacol 2014 Sep 23;74(3):559-69. Epub 2014 Jul 23.

Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, P.O. Box 30001, El-Madinah, El-Munaworah, Saudi Arabia,

Purpose: This study was undertaken to assess the possible modulatory effects and mechanisms of meloxicam, a cyclooxygenase-2 inhibitor, on the antitumor activity and cardiotoxicity of doxorubicin in a mice model of mammary carcinoma.

Methods: Solid tumor mass was developed in female albino mice using Ehrlich carcinoma cells. Forty mice-bearing tumor were divided randomly into four groups for treatment: with saline, meloxicam 10 mg/kg, doxorubicin 5 mg/kg and meloxicam 1 h ahead of doxorubicin, twice weekly for 2 weeks. Tumor volume was followed up and cardiac protective utility was estimated via measuring heart and serum parameters.

Results: Meloxicam expressed a non-significant increase in doxorubicin antitumor activity. Conversely, meloxicam significantly (p < 0.01) mitigated doxorubicin-induced elevation of serum cardiac enzymes [creatine kinase, lactate dehydrogenase and troponin-I]; cardiac lipid peroxidations marker; cardiac active caspase-3 content; and cardiac prostaglandin E2 content. Meloxicam significantly abrogated doxorubicin-induced disturbance in heart histology and relative heart weight to body weight. Meloxicam normalized doxorubicin-induced suppression in heart antioxidant enzymes activities and gene expressions [superoxide dismutase, glutathione peroxidase (GSH-Px) and catalase], and heart GSH content. In addition, meloxicam ameliorated doxorubicin-induced disturbance in phase II metabolizing enzyme, cardiac quinone reductase (QR), at activity level and mRNA expression.

Conclusion: Meloxicam protects heart against doxorubicin toxicity without affecting its antitumor activity against solid mammary cancer model in mice. This protective effect is attributed to antioxidant effect, antiradical effect, antiinflammatory action, antiapoptotic effect and induction of QR enzyme.
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http://dx.doi.org/10.1007/s00280-014-2544-3DOI Listing
September 2014

Synthesis and pharmacological activities of some new triazolo- and tetrazolopyrimidine derivatives.

Molecules 2013 Dec 6;18(12):15051-63. Epub 2013 Dec 6.

Pharmacology and Toxicology Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawara 3893, Saudi Arabia.

A new series of fused triazolo- and tetrazolopyrimidine derivatives 2-14 were synthesized and their anti-inflammatory and ulcerogenic activities were evaluated. The pharmacological screening showed that many of these obtained compounds have good anti-inflammatory activities, comparable to the reference drug. The toxicity of the compounds was also assayed via the determination of their LD50 values. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, MS spectral data and elemental analysis.
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http://dx.doi.org/10.3390/molecules181215051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269734PMC
December 2013

Anti-parkinsonism, hypoglycemic and anti-microbial activities of new poly fused ring heterocyclic candidates.

Int J Biol Macromol 2013 Jun 15;57:165-73. Epub 2013 Mar 15.

Pharmacology and Toxicology Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

A new series of poly fused pyrazolothienopyrimidine derivatives (2-14) were synthesized and their anti-parkinsonism, hypoglycemic and anti-microbial activities were evaluated. Some of the newly synthesized compounds exhibited better pharmacological and biological activities than the reference controls with low concentrations. The structures of newly synthesized compounds were confirmed by chemical, elemental and spectroscopic evidences. The detailed synthesis, spectroscopic data, and pharmacological activities were reported.
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http://dx.doi.org/10.1016/j.ijbiomac.2013.03.019DOI Listing
June 2013

Pharmacological activities of some new polycyclic triazolopyrazolopyridazine derivatives.

Int J Biol Macromol 2012 Jul-Aug;51(1-2):7-17. Epub 2012 May 8.

Pharmacy Department, College of Medical Rehabilitation Sciences, Taibah University, Madinah Munawara, Saudi Arabia.

In continuation of our previous work, a novel series of polycyclic derivatives were synthesized and their anti-inflammatory, analgesic and antimicrobial activities were evaluated. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). Some of the newly compounds exhibited better biological and pharmacological activities than the reference controls with low toxicity (LD(50)). The structure of the new compounds has been established on the bases of chemical and spectroscopic evidences. The detailed synthesis, spectroscopic data, LD(50) and pharmacological activities of the synthesized compounds were reported.
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http://dx.doi.org/10.1016/j.ijbiomac.2012.05.002DOI Listing
October 2012

Abrogation of cisplatin-induced nephrotoxicity in mice by alpha lipoic acid through ameliorating oxidative stress and enhancing gene expression of antioxidant enzymes.

Eur J Pharmacol 2011 Oct 13;668(1-2):278-84. Epub 2011 Jul 13.

Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia.

Cisplatin is chemotherapeutic drug used in treatment of malignancies. However, its clinical utility is limited by nephrotoxicity. The purpose of present study is to investigate biochemical and molecular effects of alpha lipoic acid (ALA) to protect against cisplatin-induced nephrotoxicity in mice. Cisplatin (12 mg/kg/day) was administered i.p. for 4 days. Group of mice were given ALA (20 mg/kg/day) for 18 days. Another set were administered ALA for 4 days before and 14 days after cisplatin intoxication. The results obtained revealed that kidney/body weight ratio of cisplatin-treated mice was increased by +40%. ALA intake declined the ratio by -19%. Serum creatinine and urea levels were increased in cisplatin-treated mice by +375% and +69%, respectively. These changes were moved to normalcy upon ALA intake. Cisplatin treatment elevated malondialdehyde (MDA) by 27 fold and declined reduced glutathione (GSH) by -49%. Cisplatin decreased catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes by -47%, -49% and -59%, respectively. ALA decreased the MDA by -286% and increased the GSH, catalase, SOD and GPx levels by +60%, +81%, +90% and +38%, respectively. ALA increased mRNA expression of catalase, CuZn SOD and GPx genes near to normalcy compared to cisplatin-treated mice. Cisplatin-treated mice increased caspase-3-activity by +223%, nitric oxide (NO) by +74% and inducible nitric oxide synthase (iNOS) by 10 fold. ALA intake declined these changes by -43%, -45% and -73%, respectively. ALA may play renoprotective role on cisplatin-induced nephrotoxicity through antioxidant and antiapoptotic mechanisms combined with initiation of mRNA expression of antioxidant genes.
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http://dx.doi.org/10.1016/j.ejphar.2011.06.051DOI Listing
October 2011

Schistosoma mansoni changes the activity of phase II drug-metabolizing enzymes: role of praziquantel as antibilharzial drug.

Drug Metab Lett 2010 Aug;4(3):134-8

Department of Clinical Biochemistry, Faculty of Medicine, PO Box 30001, Taibah University, Al-Madinah, Saudi Arabia.

Schistosomiasis is one of the major health problems in many developing countries and causes liver damage. In addition, under the influence of schistosomiasis most of the endogenous toxic compounds can be conjugated with glutathione via glutathione S-transferase. Therefore, the present study showed the effect of Schistosoma mansoni after 20, 30, 45, 60, and 75 days post-infection on the activity of glutathione-S-transferase (GST) and glutathione reductase (GR), and on the levels of glutathione [GSH] in the livers of male mice. In addition, anti-schistosomal drug (praziquantel) was administered orally [60 mg/kg body weight] for three consecutive days before decapitation of the infected mice at each time point. In the present, depletion of GSH levels was observed at 45, 60 and 75 days post-infection. However, treatment of infected mice at 45, 60, and 75 days post-infection with praziquantel for three consecutive days before decapitation at each time point restored the increased GSH levels to their normal values compared with control groups. Inhibition of GST and induction of GR activities in the livers of S. mansoni-infected mice at all time-points were restored to their normal levels after praziquantel treatment. It is concluded that S. mansoni infection changed the activities of GST, GR and GSH levels. Moreover, it has been found that praziquantel treatment of S. mansoni-infected mice restored such alterations to their normal values and this recovery could alleviate the deleterious effects of S. mansoni infection. In addition, the present study could provide new evidence to the damage occurred in livers of S. mansoni-infected hosts. Also, it is suggested that praziquantel is the best drug of choice for schistosoma mansoni treatment.
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http://dx.doi.org/10.2174/187231210791698447DOI Listing
August 2010

Schistsoma Mansoni Changes the Activity of Glutathione S-Transferase and Glutathione Levels in the Liver of Male Mice: Role of Praziquantel as Anti-Schistosomal Drug.

Drug Metab Lett 2010 Jun 15. Epub 2010 Jun 15.

Department of Clinical Biochemistry, Faculty of Medicine, PO Box 30001, Taibah University, Al-Madinah, Saudi Arabia.

Schistosomiasis is one of the major health problems in many developing countries and causes liver damage. In addition, under the influence of schistosomaisis, most of the endogenous toxic compounds can be conjugated with glutathione via glutathione S-transferase. Therefore, the present study showed the effect of Schistosoma mansoni after 20, 30, 45, 60, and 75 days post-infection on the activity of glutathione-S-transferase (GST) and glutathione reductase (GR), and on the levels of glutathione [GSH] in the livers of male mice. In addition, anti-schistosomal drug (praziquantel) was administered orally [60 mg/kg body weight] for three consecutive days before decapitation of the infected mice at each time point. In the present, depletion of GSH levels was observed at 45, 60 and 75 days post-infection. However, treatment of infected mice at 45, 60, and 75 days post-infection with praziquantel for three consecutive days before decapitation at each time point restored the increased GSH levels to their normal values compared with control groups. Inhibition of GST and induction of GR activities in the livers of S. mansoni-infected mice at all time-points were restored to their normal levels after praziquantel treatment. It is concluded that S. mansoni infection changed the activities of GST, GR and GSH levels. Moreover, it has been found that praziquantel treatment of S. mansoni-infected mice restored such alterations to their normal values and this recovery could alleviate the deleterious effects of S. mansoni infection. In addition, the present study could provide new evidence to the damage occurred in livers of S. mansoni-infected hosts. Also, it is suggested that praziquantel is the best drug of choice for schistosoma mansoni treatment.
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June 2010
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