Enhanced Effectiveness of Dimethyl-4,4‘-dimethoxy-5,6,5’,6‘-dimethylene dioxybiphenyl-2,2’-dicarboxylate in Combination with Garlic Oil against Experimental Hepatic Injury in Rats and Mice

Abstract

The present study was designed to evaluate the effects of dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (PMC) in combination with garlic oil against chemical-induced hepatic injury in rats and mice. Rats insulted with carbon tetrachloride were concomitantly treated with PMC and/or garlic oil (50 and 100 mg kg−1, respectively) for four weeks. Whereas treatment of animals with garlic oil alone was ineffective in suppressing carbon tetrachloride-induced hepatotoxicity, administration of PMC in combination with garlic oil more effectively protected the liver against the carbon tetrachloride-induced insult than PMC alone, as monitored by serum aminotransferase activity. Hepatoprotective effects of the formulation were further supported by the changes in the numbers of Kupffer cells and dead hepatocytes. Although prior treatment of rats with PMC for three days failed to protect hepatotoxicity elicited by allyl alcohol, the formulation of PMC and garlic oil was capable of blocking allyl alcohol-induced hepatotoxicity by ∼ 40%. To further examine the effect of the agents on lipid metabolism in the liver, hepatic triglycerides and cholesterol contents were assessed in mice after a diet containing PMC and/or garlic oil for one week followed by a single dose of carbon tetrachloride. Garlic oil appeared to be more effective in bringing hepatic lipid levels to those of control than PMC alone. Treatment of animals with PMC in combination with garlic oil synergistically improved chemical-induced impairment of hepatic triglycerides and cholesterol. These results demonstrated that PMC in combination with garlic oil is effective in protecting (or treating) chemical-induced hepatic injury and that the formulation may be effective against chemical-induced fat-infiltration of the liver.