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 HepG2 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 with 50 cGy of gamma-rays, reached a maximum at around 4 hours and returned almost to the control level by 12 hours. The effect of irradiation at 2 hours before AAP-treatment on the hepatotoxicity was then investigated in terms of glutamic pyruvic transaminase (GPT) activity in serum and lipid peroxide (malondialdehyde, MDA) content in the liver. GPT activity and MDA level were markedly increased at 24 hours post-treatment with AAP. Both increases were significantly suppressed by a single low-dose pre-irradiation with gamma-rays (50 cGy). The cellular GSH level of HepG2 cells increased about 3 hours after exposure to gamma-rays (50 cGy), peaked at 12 hours and returned almost to the time 0 value by 48 hours post-irradiation. Exposure of HepG2 cells to CHP induced time- and dose-dependent cytotoxicity, as judged from lactate dehydrogenase activity (LDH) released into the medium. Pre-irradiation with gamma-rays (50 cGy) at 6 hours before addition of 1 mM CHP to the cells significantly suppressed the elevation of LDH activity at 24 hours post-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 irradiation might be effective for the prevention of hepatotoxicity involving GSH deficiency.
Research Institute for Biological Sciences, Science University of Tokyo, Chiba, Japan. kjma@rs.noda.sut.ac.jp
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Kojima
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Shimomura
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Matsumori
D000082:Acetaminophen; D000704:Analysis of Variance; D000818:Animals; D001555:Benzene Derivatives; D002251:Carbon Tetrachloride; D005720:Gamma Rays; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D011829:Radiation Dosage; D014407:Tumor Cells, Cultured
D001555:Benzene Derivatives; D000082:Acetaminophen; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; C007164:cumene hydroperoxide