The anthocyanin cyanidin-3-O-β-glucoside modulates murine glutathione homeostasis in a manner dependent on genetic background

Anthocyanins are a class of phytochemicals that have generated considerable interest due to their reported health benefits. It has been proposed that commonly consumed anthocyanins, such as cyandin-3-O-β-glucoside (C3G), confer cellular protection by stimulating biosynthesis of glutathione (GSH), an endogenous antioxidant. Currently, it is unknown whether the health effects of dietary anthocyanins are genetically determined. We therefore tested the hypothesis that anthocyanin-induced alterations in GSH homeostasis vary by genetic background. Mice representing five genetically diverse inbred strains (A/J, 129S1/SvImJ, CAST/EiJ, C57BL/6J, and NOD/ShiLtJ) were assigned to a control or 100 mg/kg C3G diet (n=5/diet/strain) for six weeks. GSH and GSSG levels were quantified in liver, kidney, heart, pancreas, and brain samples using HPLC. The C3G diet promoted an increase in renal GSH concentrations, hepatic GSH/GSSG, and cardiac GSH/GSSG in CAST/EiJ mice. C3G treatment also induced an increase in pancreatic GSH/GSSG in C57BL/6J mice. In contrast, C3G did not affect GSH homeostasis in NOD/ShiLtJ mice. Surprisingly, the C3G-diet caused a decrease in hepatic GSH/GSSG in A/J and 129S1/SvImJ mice compared to controls; C3G-treated 129S1/SvImJ mice also exhibited lower total glutathione in the heart. Overall, we discovered that C3G modulates the GSH system in a strain- and tissue-specific manner. To our knowledge, this study is the first to show that the redox effects of anthocyanins are determined by genetic background.