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Influence of antibiotics and food intake on liver glutathione and cytochrome P-450 in septic rats

  • Virginie Colomb (a1), Jean Petit (a1), Hélène Matheix-Fortunet (a1), Bernadette Hecketsweiler (a1), Nathalie Kaeffer (a1), Eric Lerebours (a1), Raymond Colin (a1) and Jean-François Lemeland (a2)...


Experimental sepsis in rats induces a restriction in spontaneous food intake and a drop in liver glutathione, cytochrome P-450 (P-450) and aminopyrine demethylase (AD) activity. The present study was designed to assess the effects of antibiotics alone or when combined with food deprivation on these variables. Eighty-nine male Sprague-Dawley rats were assigned to six groups: control (C), acute infection (experimental pyelonephritis, I), acute infection with antibiotics and food given ad lib. (IA), control with antibiotics (CA), acute infection with antibiotics pair-fed to I (IAR), and sham-operated pair-fed to I (SR). Liver glutathione, P-450 and AD activities were reduced by 45·2, 79·8 and 41·2% respectively in group I. Glutathione and AD significantly increased only in those infected rats given antibiotics and allowed free access to food. P-450 did not normalize within the study period in infected rats receiving antibiotics and food repletion. The risk of drug hepatotoxicity in acute septic states is therefore closely related to the nutritional status. From this point of view, nutritional support is almost as important as treatment of infection.

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Baracos, V., Rodemann, H. P., Dinarello, C. A. & Goldberg, A. L. (1983) Stimulation of muscle protein degradation and prostaglandin E2 release by leucocytic pyrogen (interleukin-1). New England Journal of Medicine 308, 553558.
Beutler, E. (1989) Nutritional and metabolic aspects of glutathione. Annual Review of Nutrition 9, 287302.
Bissel, D. M. & Hammaker, L. (1976) Cytochrome P-450 heme and the regulation of hepatic heme oxygenase activity. Archives of Biochemistry and Biophysics 176, 91102.
Bock, K. W., Froling, W. & Remmer, H. (1973) Influence of fasting and hemin on microsomal cytochromes and enzymes. Biochemical Pharmacology 22, 15571564.
Boyd, M. R., Grygiel, J. J. & Minchin, R. F. (1983) Metabolic activation as a basis for organ-selective toxicity. Clinical and Experimental Pharmacology and Physiology 10, 8799.
Brooks, S. J. D., Lyons, J. M. & Braude, A. I. (1974) Immunization against retrograde pyelonephritis. I. Production of an experimental model of severe ascending Escherichia coli pyelonephritis without bacteremia in rats. American Journal of Pathology 14, 345358.
Campbell, T. C. (1977) Nutrition and drug-metabolizing enzymes. Clinical Pharmacology and Therapeutics 22, 699706.
Cho, E. I., Sahyoun, N. & Stegink, L. D. (1981) Tissue glutathione as a cyst(e)ine reservoir during fasting and refeeding of rats. Journal of Nutrition 111, 914922.
Clemens, M. G., Chaudry, I. H. & Baue, A. E. (1984) Alterations in hepatic water and electrolyte balance in sepsis. Archives of Surgery 119, 4448.
Clowes, G. H. A., George, B. C., Villee, C. A. & Saravis, C. A. (1983) Muscle proteolysis induced by a circulating peptide in patients with sepsis or trauma. New England Journal of Medicine 308, 545552.
Cooper, T. B., Simpson, G. M. & Lee, H. J. (1976) Thymoleptic and neuroleptic drug plasma levels in psychiatry: current status. International Review of Neurobiology 19, 269309.
Cox, J. E., Laughton, W. B. & Powley, T. I. (1985) Precise estimation of carcass fat from total body water in rats and mice. Physiology and Behavior 35, 905910.
Edwards, S. & Westerfeld, W. W. (1952) Blood and liver glutathione during protein deprivation. Proceedings of the Society for Experimental Biology and Medicine 79, 5759.
Ellman, G. L. (1959) Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics 82, 7077.
Feldman, C. H., Hutchinson, V. E., Pippenger, C. E., Blumenfeld, T. A., Feldman, B. R. & Davis, W. J. (1980) Effect of dietary protein and carbohydrate on theophylline metabolism in children. Pediatrics 66, 956962.
Fouin-Fortunet, H., Besnier, M. O., Colin, R., Wessely, J. Y. & Rosé, F. (1989 a) Effect of ketoacids on liver glutathione and microsomal enzymes in malnourished rats. Kidney International 36, 222226.
Fouin-Fortunet, H., Delarue, J., N'Djitoyap, C., Desechalliers, J. P., Denis, P., Lerebours, E. & Colin, R. (1990) Nutritional status modifies liver glutathione levels in man. European Journal of Gastroenterology and Hepatology 2, 271275.
Fouin-Fortunet, H., Delarue, J., Rod, F., Desechalliers, J. P., Sauger, F., Lerebours, E., Denis, P., Besnier, M. O., Wessely, J. Y. & Colin, R. (1989 b) Rehabilitation of microsomal enzymes in malnourished rats: comparison of parenteral versus oral refeeding. Clinical Nutrition 8, 101108.
Freund, H. R., Ryan, J. A. & Fischer, J. E. (1978) Amino acid derangements in patients with sepsis: treatment with branched chain amino acid-rich infusions. Annals of Surgery 188, 423430.
Ghezzi, P., Saccardo, B. & Bianchi, M. (1986 a) Recombinant tumor necrosis factor depresses P-450 dependent microsomal drug metabolism in mice. Biochemical and Biophysical Research Communications 136, 316321.
Ghezzi, P., Saccardo, B., Villa, P., Rossi, V., Bianchi, M. & Dinarello, C. A. (1986 b) Role of interleukin-1 in the depression of liver drug metabolism by endotoxin. Infection and Immunity 54, 837840.
Glauser, M. P., Lyons, J. M. & Braude, A. I. (1978) Prevention of chronic experimental pyelonephritis by suppression of acute suppuration. Journal of Clinical Investigation 61, 403407.
Gornall, A. G., Badawill, C. J. & David, M. M. (1949) Determination of serum proteins by means of the biuret reaction. Journal of Biological Chemistry 177, 751766.
Hong, J., Pan, J., Gonzales, F. J., Gelboin, H. V. & Yang, C. S. (1987) The induction of a specific form of cytochrome P-450 (P-450) by fasting. Biochemical and Biophysical Research Communications 142, 10771083.
Hum, S., Koski, K. G. & Hoffer, L. J. (1992) Varied protein intake alters glutathione metabolism in rats. Journal of Nutrition 122, 20102018.
Kaplowitz, N. (1981) The importance and regulation of hepatic glutathione. Yale Journal of Biology and Medicine 54, 497502.
Kato, R., Oshima, T. & Tomisawa, S. (1968) Toxicity and metabolism of drugs in relation to dietary protein. Japanese Journat of Pharmacology 18, 356366.
Lescut, D., Fouin-Fortunet, H., Moore, N., Petit, J., Hecketsweiler, B., Lemeland, J. F., Denis, P. & Colin, R. (1991) Liver glutathione and cytochrome P-450 activity in experimental infection: study of the relative effects of infectious stress and malnutrition. Critical Care Medicine 19, 11831187.
Long, C. L. (1988) Monokine metabolism in the septic syndrome. Journal of Parenteral and Enteral Nutrition 12, 785815.
Lorenz, J., Glatt, H. R., Fleischmann, R., Ferlinz, R. & Oesch, F. (1984) Drug metabolism in man and its relationship to that in three rodent species: monoxygenase, epoxide hydrolase, and glutathione S-transferase activities in subcellular fractions of lung and liver. Biochemical Medicine 32, 4356.
Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. (1951) Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193, 265275.
McCarthy, D. O., Kluger, M. J. & Vander, A. J. (1985) Suppression of food intake during infection: is interleukin-1 involved? American Journal of Clinical Nutrition 42, 11791182.
Maruyama, E., Kojima, K., Higashi, T. & Sakamoto, Y. (1968) Effect of diet on liver glutathione and glutathione reductase. Journal of Biochemistry 63, 398399.
Mazel, P. (1971) Experiments illustrating drug metabolism in vitro. In Fundamentals of Drug Metabolism and Drug Disposition, pp. 546582 [La Du, B. N., Mandel, H. G., Way, E. L., editors]. Baltimore: Williams and Wilkins.
Mehta, S., Kalsi, H. K., Jayaraman, S. & Mathur, V. S. (1975) Chloramphenicol metabolism in children with protein calorie malnutrition. American Journal of Clinical Nutrition 28, 977981.
Meister, A. & Tate, S. (1976) Glutathione and related α-glutamyl compounds: biosynthesis and utilisation. Annual Review of Biochemistry 45, 559604.
Mitchell, J. R., Jollow, D. J., Potter, W. Z., Gilette, J. R. & Brodie, B. B. (1973) Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. Journal of Pharmacology and Experimental Therapeutics 187, 211219.
Moldeus, P. & Quanguan, J. (1987) Importance of the glutathione cycle in drug metabolism. Pharmacology and Therapeutics 33, 3740.
Omura, T. & Sato, R. (1964) The carbon monoxide binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. Journal of Biological Chemistry 239, 23702385.
Omura, T., Sato, R. & Cooper, D. Y. (1965) Function of cytochrome P-450 of microsomes. Federation Proceedings. Federation of American Societies for Experimental Biology 24, 11811189.
Pessayre, D., Dolder, A., Artigou, J. Y. & Wandsheer, J. C. (1979) Effect of fasting on metabolite-mediated hepatotoxicity in the rat. Gastroenterology 77, 264271.
Petit, J., Fouin-Fortunet, H., Colomb, V., Hecketsweiler, B., Lemeldnd, J. F., Denis, P. & Colin, R. (1991) Liver Factors involved in drug metabolism in experimentally infected rats: deleterious effect of ornithine alpha-ketoisocaproate. Clinical Nutrition 10, 328335.
Prescott, L. F., Park, J., Sutherland, G. R.., Smith, I. J. & Proudfoot, A. T. (1976) Cysteamine, methionine, and penicillamine in the treatment of paracetamol poisoning. Lancet ii, 109113.
Remmer, H. (1972) Induction of drug metabolising enzyme system in the liver. European Journal of Clinical Pharmacology 5, 116136.
Renton, K. W. & Mannering, G. J. (1976) Depression of hepatic cytochrome P-450-dependent monooxygenase systems with administered interferon inducing agents. Biochemical and Biophysical Research Communications 73, 343348.
Robinson, M. K., Rounds, J. D., Hong, R. W., Jacobs, D. O. & Wilmore, D. W. (1992) Glutathione deficiency increases organ dysfunction after hemorrhagic shock. Surgery 112, 140149.
Roh, M. S., Moldawer, L. L., Ekman, L. A, Dinarello, C. A, Bistrian, B. R., Jeevanandam, M. & Brennan, M. F. (1986) Stimulatory effect of interleukin-1 upon hepatic metabolism. Metabolism 35, 419424.
Roth, E., Muhlbacher, F., Karner, J. & Steininger, R. (1985) Liver amino acids in sepsis. Surgery 97, 436&442.
Schreiber, G., Howlett, G., Nagashima, M., Millership, A., Martin, H., Urban, J. & Kotler, L. (1982) The acute-phase response of plasma protein synthesis during experimental inflammation. Journal of Biological Chemistry 257, 1027110277.
Sherlock, S. (1979) Hepatic reactions to drugs. Gut 20, 634648.
Tateishi, N., Higashi, T., Shinya, S., Naruse, A. & Sakamoto, Y. (1974) Studies on the regulation of glutathione level in rat liver. Journal of Biochemistry 75, 93103.
Vasko, M. R. & Brater, D. C. (1989) Drug interactions. In Essentials of Critical Care Pharmacology, pp. 126 [Chernow, B., editor]. Baltimore: Williams and Wilkins.
Wade, A. E., White, R. A, Walton, L. C. & Bellows, J. T. (1985) Dietary fat- a requirement for induction of mixed-function oxidase activities in starved-refed rats. Biochemical Pharmacology 34, 37473754.
Ward, M. W. N., Owens, C. W. I. & Rennie, M. J. (1980) Nitrogen estimation in biological samples by use of chemiluminescence. Clinical Chemistry 26, 13361339.
Warnet, J. M., Bakar-Wesseling, l. & Thevenin, M. (1987) Effects of subchronic low-protein diet on some tissue glutathione related enzyme activities in the rat. Archives of Toxicology Suppl. 11, 4549.
White, P. F., Way, W. L. & Trevor, A. J. (1982) Ketamine. Its pharmacology and therapeutic uses. Anesthesiology 56, 119136.
Yang, C. S., Brady, J. F. & Hong, J.-Y. (1992) Dietary effects on cytochromes P-450, xenobiotic metabolism, and toxicity. FASEB Journal 6, 737744.



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