Effect of pre-irradiation with low-dose gamma-rays on chemically induced hepatotoxicity and glutathione depletion

We examined the elevation of glutathione (GSH) level in mouse liver and Hep G2 cells after low-dose gamma-ray irradiation and its inhibitory effect on acetaminophen (AAP)-and cumene hydroperoxide (CHP)-induced hepatotoxicity. The liver GSH level in male ddY mice increased 2 hours after irradiation wi th 50 cGy of gamma-rays, reached a maximum at around 4 hours and returned a lmost to the control level by 12 hours. The effect of irradiation at 2 hour s before AAP-treatment on the hepatotoxicity was then investigated in terms of glutamic pyruvic transaminase (GPT) activity in serum and lipid peroxid e (malondialdehyde, MDA) content in the liver GPT activity and MDA level we re markedly increased at 24 hours post-treatment with AAP. Both increases w ere significantly suppressed by a single low-dose pre-irradiation with gamm a-rays (50 cGy). The cellular GSH level of HepG2 cells increased about 3 ho urs after exposure to gamma-rays (50 cGy), peaked at 12 hours and returned almost to the time a value by 48 hours post-irradiation. Exposure of HepG2 cells to CHP induced time- and dose-dependent cytotoxicity, as judged fr om lactate dehydrogenase activity (LDH) released into the medium. Pre-irradia tion with gamma-rays (50 cGy) at 6 hours before addition of I mM CHP to the cells significantly suppressed the elevation of LDH activity at 24 hours p ost-treatment. In both cases the lowered GSH levels induced by AAP and CPH appeared to be restored to the control level by pre-irradiation with a low dose of gamma-rays. These results suggest that low-dose gamma-ray irradiati on might be effective for the prevention of hepatotoxicity involving GSH de ficiency.