Exogenous Ascorbate Administration Elevates Testicular Oxidative Damage and Histological Injuries in Rats after Busulfan Treatment

Abstract

Several anticancer drugs are coadministered with ascorbate (ASCB) to complement their cytotoxic effects. However, it is not known if the treatment regimen prevents collateral oxidative damage to non-target sites. The current study evaluated the effect of ASCB cotreatment on the testes of young adult rats treated with an anticancer drug, busulfan (BUS). About 40 Wistar rats were arbitrarily assigned into four groups (N = 10), namely, control (<0.2% dimethyl sulfoxide vehicle), BUS (4 mg/kg b.w.; intraperitoneally for 4 days), BUS + ASCB (4 mg BUS/kg b.w. for 4 days + 100 mg ASCB/kg b.w.; intraperitoneally for 14 days and 7 days prior to start of BUS injection), and ASCB (100 mg/kg b.w.; intraperitoneally for 21 days). At the end of study, ASCB + BUS cotreatment reduced spermatogenesis score index, superoxide dismutase activity, total ASCB and decreased hydrogen peroxide level, and elevated catalase activity and nitrite concentration much more than treatment with BUS alone (P < 0.05). Other observations included elevated malondialdehyde level, DNA damage, and diminished glutathione concentration in the testes of BUS + ASCB animals. Interestingly, ASCB administration raised testicular ASCB concentration beyond the control values (P < 0.05) and the antioxidant status of the testes. Histological aberrations included many single layers of germ cells, shrinked tubules, and vacuolated structures in the epithelium of BUS + ASCB, similar to those of BUS-treated animals. In conclusion, BUS treatment deregulated the redox status of the testes and caused a dramatic consumption of ASCB which were enhanced by exogenous ASCB resulting to testicular damage.