The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice.

Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA), and/or their fixed-dose combination (FDC) are extensively prescribed in the cure of Tuberculosis (TB) globally. In spite of the beneficial effect, these drugs are capable of inducing cellular toxicity. Existing information on the genotoxic effects of the first-line anti-TB drugs is limited and contentious. Herein, we evaluated the reproductive genotoxicity of RIF, INH, EMB, PZA, and their FDC utilizing the mouse sperm morphology assay. Histological examination of the testes of exposed mice was also performed. Male Swiss albino mice (11-13 weeks old) were intraperitoneally exposed for 5 consecutive days to each of the anti-TB drugs at four different doses of 6.25, 12.5, 25, and 50 mg/kg bw of PZA; 2.5, 5.0, 10, and 20 mg/kg bw of RIF; 1.25, 2.5, 5.0 and 10 mg/kg bw of INH; 3.75, 7.5, 15 and 30 mg/kg bw of EMB; and 7, 14, 28 and 56 mg/kg bw of FDC corresponding respectively to ×0.25, ×0.5, ×1 and ×2.0 of the standard daily dose. In comparison with the negative control (normal saline), there was no significant difference in the testicular weight and organo-somatic index of exposed mice. There was an increase (p > 0.05) in the frequency of abnormal spermatozoa at most of the tested doses of each drug and a dose-dependent decrease with the FDC. Each of the anti-TB drugs except the FDC induced pathological lesions in the testes. These findings suggest that the individual first-line anti-TB drug unlike the FDC has the potential to provoke testicular anomalies in male mice.

Metal Bioaccumulation, Cytogenetic and Clinico-Biochemical Alterations in Rattus norvegicus Exposed In Situ to a Municipal Solid Waste Landfill in Lagos, Nigeria.

This study aimed at determining in animal model the health effects of in situ exposure to landfill chemicals. We evaluated metal concentrations in tissues and cytogenetic and clinico-biochemical effects in Wistar rats (Rattus norvegicus) exposed in situ at Olusosun landfill in Lagos, Nigeria. Male rats (n = 30/point) were exposed at three different points to ambient air and underground water (via drinking) at the landfill for 4-, 8-, 12-, 16-, 20- and 24-week periods. Rats concurrently sited at a residential area, 17.3 km from the landfill site served as control. There was significantly (p < 0.05) time-dependent: accumulation of lead, cadmium, chromium, copper and zinc in the liver and kidney and increase in body weight gain, in exposed rats compared to control. There was significant induction of micronuclei and cytotoxicity (reduced PCE/NCE ratios) in exposed rats. Haematological parameters (RBC, PCV, Hb and WBC) and serum biomarkers of hepato-renal damage [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activities; creatinine and urea levels] revealed significant increases. There was significant increase in hepatic levels of reduced glutathione, malondialdehyde, catalase activities, and decrease in superoxide dismutase, at all periods. Chromium and copper concentrations in the liver and kidney revealed significant positive correlations with either one or more of AST, ALT, LDH and urea. Significant metal concentrations in the underground water and tissues suggest that heavy metals are responsible for the observed alterations, and this may have been via oxidative stress. These findings suggest potential health risk due to occupational and residential exposure to landfill pollutants.