Biochemical aspects of the protective action of propyl gallate on liver injury in rats poisoned with carbon tetrachloride

Abstract

Liver injury in rats intoxicated with a high dose of CCl 4 (2.5 ml/kg, po) is partially prevented by propyl gallate. The accumulation of hepatic triglycerides and the release of liver enzymes into the plasma are more effectively inhibited by this antioxidant in rats given a smaller dose of the hepatotoxin (0.25 ml/kg, po). The antioxidant activity of propyl gallate, administered in vivo, estimated by means of the production of malonyl dialdehyde in liver homogenates in vitro, has been found to decrease progressively after treatment. The concentration of nonesterified fatty acids in the serum is not affected by dosing with propyl gallate. However, propyl gallate releases the block in triglyceride secretion from the liver that occurs after administration of CCl 4. Furthermore, both the uptake of CCl 4 by the liver and the early steps of the free radical reaction (incorporation of labeled metabolites of 14CCl 4 and double bond shifting in microsomal unsaturated lipids) are unchanged by concomitant dosing with propyl gallate. This free radical scavenger, when administered in discrete doses, more markedly influences both CCl 4 liver damage and the efficiency of the hepatic drug metabolizing enzyme system. This effect in vivo is consistent with the reported in vitro interaction of propyl gallate with microsomal electron transport. These findings indicate that propyl gallate partially interferes with the enzymes bound to the endoplasmic reticulum, but affects the secondary phenomena of lipid peroxidation at the level where lipoproteins are secreted and/or the permeability of plasma membrane is altered.