Summary
Rats given a dose of carbon tetrachloride (CCl4) immediately received injections of glucagon and insulin every 4h. They frequently died after 4h and showed a significantly higher mortality between 8h and 28h as compared to the control rats where such deaths occurred 16h later. At 8h, the derangements of SGPT values and prothrombin time were significantly greater in the hormone-treated rats than in the control rats. In these CCl4-intoxicated rats, hepatic reduced glutathione content at 4h was significantly reduced after hormone treatment. The treatment significantly enhanced CCl4 metabolism, conversion of14CCl4 into14CO2 in vitro, by microsomes isolated from the liver, whereas it did not affect the microsomal cytochrome P450 content. These results suggest that glucagon and insulin treatment increased CCl4 hepatotoxicity in rats through activating the cytochrome P450-dependent mono-oxygenase system. This would merit consideration for the clinical application of this treatment.
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References
Armbrecht HJ, Birnbaum LS, Zenser TV, Davis BB (1982) Changes in hepatic microsomal membrane fluidity with age. Exp Gerontol 17:41–48
Baker AL, Jaspan JB, Haines NW, Hatfield GE, Krager PS, Schneider JF, The University of Chicago Medical Housestaff (1981) A randomized clinical trial of insulin and glucagon infusion for treatment of alcoholic hepatitis: Progress report in 50 patients. Gastroenterology 80:1410–1414
Farivar M, Wands JR, Isselbacher KJ, Bucher NLR (1976) Effect of insulin and glucagon on fulminant murine hepatitis. N Engl J Med 295:1517–1519
Harper AE (1963) Glucose-6-phosphatase. In: Bergmeyer H-U (ed) Methods of enzymatic analysis. Academic Press, New York London, pp 788–792
Hasumura Y, Teschke R, Lieber CS (1974) Increased carbon tetrachloride hepatotoxicity, and its mechanism, after chronic ethanol consumption. Gastroenterology 66:415–422
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Oka H, Okita K, Fujiwara K (1982) Glucagon and insulin therapy in fulminant hepatic failure in Japan. In: Picazo J (ed) Glucagon in gastroenterology and hepatology. Pharmacological, clinical, and therapeutic implications. MTP Press, Lancaster, pp 171–180
Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239:2370–2378
Seawright AA, McLean AEM (1967) The effect of diet on carbon tetrachloride metabolism. Biochem J 105:1055–1060
Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 25:192–205
Slater TF (1978) Biochemical studies on liver injury. In: Slater TF (ed) Biochemical mechanisms of liver injury. Academic Press, London New York San Francisco, pp 1–44
Strobel HW, Lu AYH, Heidema J, Coon MJ (1970) Phosphatidylcholine requirement in the enzymatic reduction of hemoprotein P-450 and in fatty acid, hydrocarbon, and drug hydroxylation. J Biol Chem 245:4851–4854
Tribble DL, Aw TY, Jones DP (1987) The pathophysiolgical significance of lipid peroxidation in oxidative cell injury. Hepatology 7:377–387
Zimmerman HJ (1976) Experimental hepatotoxicity. In: Eichler O (ed) Handbook of experimental pharmacology, vol 16: Experimental production of diseases, p5: Liver. Springer, Berlin Heidelberg New York, pp 1–120
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Masaki, N., Yamada, S., Ogata, I. et al. Enhancement of carbon tetrachloride-induced liver injury by glucagon and insulin treatment. Res. Exp. Med. 188, 27–33 (1988). https://doi.org/10.1007/BF01852091
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DOI: https://doi.org/10.1007/BF01852091