The protective effect of taurine on cyclophosphamide-induced testicular toxicity in rats.

This study aimed to evaluate the protective effect of taurine (TAU) with regard to antioxidant, anti inflammatory and antiapoptotic pathways on cyclophosphamide (CP)-induced testicular toxicity in rats. Forty Sprague-Dawley male rats were used in this experimental study. The CP group animals received a single dose of 200mg/kg CP on Day 8 intraperitoneally (i.p). The other groups were treated with TAU (75, 150 and 300mg/kg) orally for 14 days prior to and following a single i.p injection of CP. Morphometrical analysis and histological examination of testicular tissue were performed. Serum testosterone, LH and FSH levels were measured in serum using commercial ELISA kits. The testicular injury induced by CP was evaluated in terms of oxidative stress, inflammation and apoptosis with a significant inflammatory and apoptotic response and an insignificant oxidative stress. TAU treatment resulted in improvement in body weight gain, oxidative stress, inflammation and apoptosis, some of which were significant. The improvement was more pronounced for antiapoptotic effect of taurine in the testis of CP-treated animals. It was concluded that TAU may prevent and/or treat the testicular toxicity by ameloirating oxidative stress, inflammation and apoptosis.

Effect of CYP3A5 and ABCB1 Gene Polymorphisms on Tacrolimus Blood Concentration in Renal Transplant Recipients.

BACKGROUND: Tacrolimus (Tac) is a calcineurin inhibitor (CNI). Its therapeutic range is narrow and pharmacokinetic properties vary among patients. CYP3A5 and MDR1 single-nucleotide polymorphisms (SNPs) are the most effective polymorphisms that play an significant role in the pharmacokinetics of Tac. METHODS: We investigated the influence of CYP3A5 (A6986G) and MDR1 (C3435T) gene polymorphisms on Tac trough concentration (C0), dose requirements (mg/kg), and dose-adjusted concentrations (ng/mL per mg/kg/d). CYP3A5 [*1/*1 (expresser), *1/*3 (expresser); *3/*3 (non-expresser)] and MDR1 (CC, CT, TT) gene polymorphisms were determined by allele-specific polymerase chain reaction in 67 adult Turkish renal transplant patients. The Tac dose (mg/kg/d) and C0 of each patient was acquired from the patient's file and dose-adjusted concentrations (ng/mL per mg/kg/d) were calculated at the 1st, 3rd, 6th, and 12th months after transplantation. The correlated serum hematocrit, platelet, urea, creatinine, and albumin were also determined. RESULTS: The CYP3A5*1/*3 and CYP3A5*3/*3 allelic frequencies were 5.97% and 94.03%, respectively. There were no patients with the CYP3A5*1/*1 genotype. Tac dose was significantly lower in *3/*3 genotype than in *1/*1 genotype (3rd and 6th months: p ≤ 0.001; 12th month: p ≤ 0.05). Dose-adjusted Tac concentration was statistically higher in the *3/*3 genotype than in *1/*1 genotype at the 3rd and 6th months (p ≤ 0.05). The allelic frequencies of MDR1 CC, CT, and TT were 26.87%, 49.25%, and 23.88%, respectively. No statistically significant differences were detected between MDR1 genotypes and in all analyzed laboratory parameters. CONCLUSIONS: CYP3A5 but not MDR1 genetic polymorphisms affected the Tac pharmacokinetics and dose requirements in renal transplant recipients. Pharmacogenetic methods can be used for selecting the initial dose to individualize immunosuppressive therapy.