Ginseng intestinal metabolite-I (GIM-I) reduces doxorubicin toxicity in the mouse testis

The protective effect of ginseng intestinal metabolite-I (GIM-I) against doxorubicin-induced testicular toxicity was investigated in 5-week-old ICR male mice. GIM-I was administered orally to mice at a dose of 50 mg/kg daily for 4 weeks. From the second week, doxorubicin was coadministered intraperitoneally to the animals at a dose of 3 mg/kg once a week for 3 weeks (a total of 9 mg/kg). The body weight, spermatogenic activities (Sertoli cell, repopulation, and epididymal indices), and serum levels of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) were significantly decreased by doxorubicin treatment (P<0.01), while the combined treatment of GIM-I with doxorubicin resulted in parameters similar to the control. In the testes of doxorubicin-treated animals, almost all of the germ cells disappeared and were replaced by fibrinoid debris in the seminiferous tubules. Germ cell injury was significantly attenuated by GIM-I coadministration. The mRNA for phospholipid hydroperoxide glutathione peroxidase (PHGPx), a testis-specific antioxidant, was greatly decreased by doxorubicin treatment, and less decreased with GIM-I coadministration. These findings indicate that GIM-I may be partially protective against doxorubicin-induced testicular toxicity.