Taurine protects rat testes against doxorubicin-induced oxidative stress as well as p53, Fas and caspase 12-mediated apoptosis

Abstract

The protective effect of taurine against doxorubicin-induced testicular oxidative stress and apoptosis was investigated in rats. Male rats 8 weeks of age were treated with doxorubicin alone (3 mg/kg, i.p. every other day for 3 doses), taurine alone (150 mg/kg, i.p. every other day for 3 doses) or taurine plus doxorubicin (each dose given 1 day post-taurine). After 28 days, rat testes were collected and analysed. Rats treated with doxorubicin alone displayed reduced body and testicular weights, decreased sperm counts, increased the extent of testicular toxicity (as evident from the decreased activity of testicular marker enzyme, SDH) and oxidative stress (reduced GSH, increased GSSG and MDA levels), decreased antioxidant (SOD, CAT, GST, GPx, GR) and membrane-bound (Na+-K+ and Ca2+ ATPases) enzyme activities as well as plasma testosterone. Reverse transcriptase-PCR analysis revealed that doxorubicin induced a marked decrease in the expression of key enzymes for testicular androgenesis (3β-HSD, 17β-HSD) and testicular steroidogenic acute regulatory (StAR) protein. Western blot analysis showed that doxorubicin administration markedly increased the levels of caspase-9, 3, -8, -12, Fas, Bid and disturbed the Bcl-2 family protein balance. These results suggest that doxorubicin can trigger intrinsic, extrinsic and endoplasmic reticulum-associated apoptotic pathways in testicular pathophysiology. Doxorubicin also triggered activation of JNK, p38MAP kinases and p53. However, taurine could effectively prevent nearly all of these doxorubicin-induced testicular abnormalities, thereby proving to be an effective cytoprotectant.