Affiliation:
1. Drug Metabolism and Toxicology Research Laboratories , Department of Biochemistry , University of Ibadan , Ibadan , Nigeria
2. Faculty of Basic Medical Sciences, Department of Medical Microbiology and Parasitology , University of Ibadan , Ibadan , Nigeria
3. Department of Medical Microbiology and Parasitology , University College Hospital , Ibadan , Nigeria
4. Drug Metabolism and Toxicology Research Laboratories , Department of Biochemistry, University of Ibadan , Ibadan , Nigeria , Phone: +234-81-6304-7157, E-mail:
Abstract
Abstract
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.
Methods:
Thirty-five female Wistar rats were assigned into five groups of seven animals each. The control group received normal saline, whereas others received INH (5 mg/kg), RIF (10 mg/kg), EMB (15 mg/kg), and PZA (15 mg/kg) through gavage thrice a week for 8 consecutive weeks.
Results:
Administration of anti-TB drugs significantly (p<0.05) reduced uterine and ovarian weight, as well as the relative weight of the uterus when compared with controls. In addition, anti-TB drugs increased the activities of alanine aminotransferase as well as the level of total bilirubin. Treatment with INH, RIF, and PZA significantly (p<0.05) reduced the levels of follicle-stimulating and luteinizing hormones, estrogen, and prolactin. The INH, RIF, EMB, and PZA caused significant (p<0.05) increases in uterine malondialdehyde (MDA) levels by 281%, 214%, 273% and 190%, respectively, whereas INH and EMB increased the ovarian malondialdehyde by 111% and 129%, respectively. These drugs significantly (p<0.05) decreased the activities of ovarian glutathione-S-transferase and uterine glutathione peroxidase, superoxide dismutase, and catalase. Histology revealed the erosion of uterine mucosa, debris in the lumen of the uterus, congestion, and underdeveloped follicles in ovaries.
Conclusions:
The first-line anti-TB drugs elicited reproductive toxicity in the uterus and ovaries of rats through mechanisms that involved oxidative stress.
Subject
Drug Discovery,Pharmacology,General Medicine,Physiology
Reference43 articles.
1. Madhavi M, Samudruam P, Hemanth A, Lalitha V. Effect of antioxidant vitamins C and E supplementation its plasma levels and on lipid profile in pulmonary tuberculosis patients. Am J Infect Dis 2009;5:263–72.
2. World Health Organization. Reproductive health strategy to accelerate progress towards the attainment of international development goals and targets. http://whqlibdoc.who.int/hq/2004/WHO_RHR_04.8.pdf. 2004.
3. Adekambi T, Ibegbu CC, Kalokhe AS, Yu T, Ray SM, Rengarajan J. Distinct effector memory CD4+ T cell signatures in latent Mycobacterium tuberculosis infection, BCG vaccination and clinically resolved tuberculosis. PLoS One 2012;7:e36046.
4. World Health Organization. Global tuberculosis report: Epidemiology. Geneva: World Health Organization, WHO/HTM/TB/2015.22, 2015.
5. De Backer AI, Mortele KJ, Keulenear BL, Parizel PM. Tuberculosis: epidemiology, manifestation, and the value of medical imaging in diagnosis. JBR-BTR 2006;89:143–50.
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