Down-regulation of CatSper 1 and CatSper 2 genes by lead and mercury.

In the study of the expression of CatSper genes, consideration of the effects of environmental metal toxicity is very important. Therefore, in this study, the effects of lead acetate and mercury chloride exposure on expression of CatSper genes, sperm parameters, histology of testis and prooxidant antioxidant balance (PAB) values of serum were investigated. A total of 28 mice was divided into four groups. The control group did not receive injections. The sham group received normal saline intraperitoneally. Lead and mercury groups were injected 60 and 1.25 mg/kg/daily lead acetate and mercury chloride respectively intraperitoneally for 2 weeks. After 35 days, the sperm analysis and histology of left testis were performed. In addition, serum was obtained to measure the PAB values. The right testis was used for molecular analysis of real-time PCR. Administration with either lead acetate or mercury caused significant damage to the seminiferous tubules as well as a reduction in sperm parameters compared to the control group. The relative expression of CatSper 1 and CatSper 2 in the lead group was lower than that of the control group (-0.01 ±â€¯0.24, -0.007 ±â€¯0.52 vs. 1 ±â€¯0.50, P = 0.34). The relative expression of CatSper 1 and CatSper 2 was significantly lower in the mercury group compared to the control ones (-0.24 ±â€¯2.28, -4.49 ±â€¯4.86 vs. 1 ±â€¯0.50, P = 0.21). PAB values significantly increased in lead or mercury exposed- mice compared to the control ones (0.93 ±â€¯0.17, 1.54 ±â€¯0.17 vs. 0.51 ±â€¯0.11; P ≤ 0.000). The results of this study showed that administration with either lead acetate or mercury chloride caused degenerative damage in seminiferous tubules and reduction in sperm quality and expression of CatSper 1, 2 genes in mice. Therefore, it is possible in infertile men who have had exposure to lead acetate or mercury chloride. Owing to structural similarities, these metals are substitutes for calcium ions and have effects on calcium channels. These cause immobility in sperm by blocking CatSper-specific calcium channels. However, more studies are required to elucidate the mechanism underlying the impact of different doses of heavy metals on CatSper genes expression.

Study of oxidative-stress in isoniazid-rifampicin induced hepatic injury in young rats.

The role of oxidative-stress as a mechanism of hepatotoxicity caused by combination of isoniazid (INH) and Rifampicin (RMP) was investigated in young growing rats. A successful model of hepatotoxicity was produced by giving 50 mg/kg/day each of INH and RMP in two weeks. Liver showed type II hepatocellular changes (microvesicular fat deposition) with mild portal triaditis. The glutathione and related thiols were significantly decreased in both blood and liver tissues with combination of INH and RMP treatment. Superoxide dismutase, glutathione peroxidase, catalase and glutathione-S-transferases with CDNB and DCNB as substrates were decreased in the combination treated group. Glutathione reductase, glutathione-S-transferase with ethacrynic acid as substrate and lipid peroxidation exhibited a significant increase with treatment. The altered profile of antioxidant enzymes with increased lipid peroxidation indicated the enhanced oxidative-stress in combination of INH and RMP treatment. All the findings are faithfully reflected in the blood tissue except superoxide dismutase which showed significant enhancement in this tissue. INH and RMP hepatotoxicity is thus appeared to be mediated through oxidative-stress.