CYTOTOXICITY OF PROPYL GALLATE AND RELATED-COMPOUNDS IN RAT HEPATOCYTES

The cytotoxic effects of propyl gallate (PG), its related gallates and gallic acid have been studied in freshly isolated rat hepatocytes. Ad dition of PG (0.5-2.0 mM) to hepatocyte suspension elicited concentrat ion-dependent eel death accompanied by losses of intracellular ATP, ad enine nucleotide pools, glutathione (GSH) and protein thiols. The rapi d loss of intracellular ATP preceded the onset of cell death caused by PG. In the comparative toxic effects of PG and related gallates at co ncentration of 1 mM, octyl gallate (OG), dodecyl gallate (DG) and buty l gallate (BG) elicited an abrupt depletion of ATP, followed by an acu te cell death. These gallates were more toxic than PG; the toxic effec ts of PG were similar to those of methyl gallate (MG) and ethyl gallat e (EG). In mitochondria isolated from rat liver, PG caused a concentra tion-dependent increase in the rate of state 4 oxygen consumption, ind icating an uncoupling effect. The rate of state 3 oxygen consumption w as inhibited by OG and DG. According to the respiratory control index, the order of impairment potency to mitochondria was OG > BG, DG > PG > EG, MG > gallic acid. These results indicate that PG and related gal lates are toxic to hepatocytes and that the acute cytotoxicity may be due to mitochondrial dysfunction.