Burczynski FJ, Yan J, Gong Y, Nguyen D, Wang G, Burczynski SD, Smith HJ and Gong Y
The clinical use of diltiazem has been suggested to be a reasonable approach for combating free radical induced liver damage. The hepatoprotective effect was observed with d-cis diltiazem but not with l-cis diltiazem, suggesting that diltiazem is stereospecific in protecting against lipid peroxidation using isolated microsomes. In the present work we examined d-cis diltiazem’s antioxidant property using Chang and PLC hepatocyte cultures, and the combination of diltiazem and silymarin since silymarin itself has been reported to possess hepatoprotectant properties. Diltiazem (5 and 10 μM) significantly reduced free radical levels, as did silymarin. The combination of diltiazem and silymarin further protected cells against oxidative stress (p<0.001) compared to either drug alone. Diltiazem, silymarin and the combination were associated with enhanced ATP and reduced Bax and Bax mRNA levels in both cell types with the combination drug treatment showing a much greater difference. The combination of dilitiazem and silymarin further enhanced cell viability. We conclude that low dose diltiazem and silymarin can function as a hepatoprotectant against free radical damage due to oxidative stress. The protective nature extends to reducing levels of the pro-apoptotic Bax protein.
