Dose-response effect of polyphenon-60 from green tea (P60-GT) on hexavalent chromium-induced genotoxic damage and apoptosis in mice.

Abstract

This study aimed to examine the dose-response effects of polyphenon-60 derived from green tea (P60-GT) on hexavalent chromium [Cr(VI)]-induced genotoxic damage and apoptosis. Male Hsd:ICR mice were divided into 4 groups: (1) Control (vehicle only), (2) P60-GT (15, 30, or 45 mg/kg gavage), (3) Cr(VI) (20 mg/kg of CrO₃ intraperitoneally), and (4) P60-GT+CrO₃ (P60-GT administered 4 hr before CrO₃). Peripheral blood samples were collected at 24, 48, and 72 hr to assess the number of micronuclei (MN), apoptosis, and cell viability, while plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured at 0 and 48 hr. Cr(VI) significantly increased MN frequency, suppressed 8-OHdG repair, and reduced cell viability. Pre-treatment with P60-GT reduced MN frequency by up to 74%, with the 30 mg/kg dose demonstrating the highest efficacy. This dose restored cell viability, enhanced 8-OHdG repair, and enhanced apoptosis, suggesting activation of DNA repair and apoptotic pathways as potential antigenotoxic mechanisms. The 15 mg/kg dose exhibited anti-apoptotic effects, while the 30 and 45 mg/kg doses promoted apoptosis. However, the 45 mg/kg dose resulted in 100% lethality by 72 hr, likely due to synergistic toxicity with Cr(VI). These findings demonstrate the dose-dependent protective effects of P60-GT and emphasize the need for dosage optimization to maximize therapeutic benefits while minimizing toxicity.