Hostname: page-component-7479d7b7d-t6hkb Total loading time: 0 Render date: 2024-07-11T23:32:40.378Z Has data issue: false hasContentIssue false
  • English
  • Français

Different levels of Schistosoma mansoni infection induce changes in drug-metabolizing enzymes

Published online by Cambridge University Press:  05 June 2009

S.A. Sheweita ,
S.A. Mangoura  and
A.G. El-Shemi
S.A. Sheweita
Affiliation:
Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, PO Box 832, Alexandria, Egypt
S.A. Mangoura
Affiliation:
Department of Pharmacology, Faculty of Medicine, Assiut University, Assuit, Egypt
A.G. El-Shemi
Affiliation:
Department of Pharmacology, Faculty of Medicine, Assiut University, Assuit, Egypt
Get access Rights & Permissions [Opens in a new window]

Abstract

Most carcinogens and xenobiotics are metabolized primarily by the mixed function oxidase system which includes cytochrome P450, cytochrome b5, NADPH-cytochrome c reductase and aryl hydrocarbon [benzo(a)pyrene] hydroxylase. The present study investigates the influence of infection with different levels of Schistosorna mansoni cercariae on the hepatic levels of reduced glutathione, glutathione S-transferase and glutathione reductase in addition to the enzymes of mixed function oxidase. Cercariae infection levels of 60, 120, 180, 300 and 600 per mouse increased: (i) the hepatic content of cytochrome P450 by 27%, 38%, 72%, 57%, 48% respectively; (ii) the aryl hydrocarbon hydroxylase activity by 44%, 64%, 76%, 90%, 51% respectively; and (iii) the hepatic level of reduced glutathione by 67%, 83%, 103%, 60%, 38% respectively. The cytochrome b5 content did not change at the lowest level of infection but increased at the other four levels by 45%, 76%, 49% and 38% respectively. The activity of glutathione S-transferase increased at the first three levels by 42%, 40%, 27% respectively and decreased at the last two levels by 28% and 52% respectively. On the other hand, the activity of glutathione reductase did not change at any level, whereas, NADPH-cytochrome c reductase activity decreased at the last two levels by 44% and 54%. The alterations in the activities of phase I & II of drug-metabolizing enzymes as a result of infection with different levels of S. mansoni may thus change the liver's capacity to detoxify many endogenous compounds and may also potentiate the deleterious effects of aromatic hydrocarbons, e.g. benzo(a)pyrene, upon the liver and probably other organs. Such alterations may also change the therapeutic actions of drugs that are primarily metabolized by the P450 system, when administered to patients with schistosomiasis.

Type
Research Papers
Information
Journal of Helminthology , Volume 72 , Issue 1 , March 1998 , pp. 71 - 78
Copyright
Copyright © Cambridge University Press 1998

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Badawi, A.F., Mostafa, M.H., Boul-Azm, T., Haboubi, N.Y., O'Connor, P.J. & Cooper, D.P. (1992) Promutagenic methylation damage in bladder DNA from patients with bladder cancer associated with schistosomiasis and from normal individuals. Carcinogenesis 13, 877–881.CrossRefGoogle ScholarPubMed
Badawi, A.F., Cooper, D.P., Mostafa, M.H., Doenhoff, M.J., Probert, A., Fallon, P., Cooper, R. & O'Connor, P.J. (1993) Promutagenic methylation damage in liver DNA of mice infected with Schistosoma mansoni. Carcinogenesis 14, 653–657.CrossRefGoogle ScholarPubMed
Brauze, D., Mikstacka, R. & Baer-Dubowska, M. (1991) Formation and presence of benzo(a)pyrene-DNA adducts in different tissues of C57 BL/10 and DBA/2 mice. Carcinogenesis 12, 1607–1611.CrossRefGoogle Scholar
Byram, J.E., Doenhoff, M.J., Musallam, R., Brink, L.H. & Von Lichenberg, F. (1979) Schistosoma mansoni infections in T-cell deprived mice and the ameliorating effect of administrating homologous chronic infection serum. American Journal of Tropical Medicine and Hygiene 28, 274–285.CrossRefGoogle ScholarPubMed
Cheever, A.W. & Andrade, Z.A. (1967) Pathological lesions associated with S. mansoni in man. Transactions of the Royal Society of Tropical Medicine and Hygiene 61, 626–639.CrossRefGoogle Scholar
Cheever, A., Kuntz, R. & Moor, J. (1979) Carcinoma of the urinary bladder in Schistosoma haematobium infection. Animal model: proliferative urothelial lesions in nonhuman primates infected with Schistosoma haema tobium. American Journal of Pathology 84, 673–676.Google Scholar
Connely, J.C. & Bridges, J.W. (1982) The distribution and role of cytochrome P450 in extrahepatic organs. pp. 1–112in Bridges, J.W. & Chasseaud, I.F. (Eds) Progress in drug metabolism. Chichester, Wiley.Google Scholar
Conney, A.H. (1982) Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons. Cancer Research 42, 4875–4917.Google ScholarPubMed
Dimmette, R., Elwi, A. & Sproat, H. (1956) Relationship of schistosomiasis and adenocarcinoma of large intestine. American Journal of Clinical Pathology 26, 266–276.CrossRefGoogle ScholarPubMed
Domingo, E.O., Warren, K.S. & Stenger, R.J. (1967) Increased incidence of hepatoma in mice with chronic schistosomiasis mansoni treated with a carcinogen. American Journal of Pathology 51, 307–321.Google ScholarPubMed
El-Bassiouni, E.A., Mostafa, M.H. & El-Sewedy, S.M. (1984) Hepatic microsomal enzymes in Schistosoma mansoni infected mice. II. Effects of duration of infection and lindane administration on aminopyrene demethylase and aniline hydroxylase. Journal of Environmental Science and Health 19, 193–207.CrossRefGoogle Scholar
El-Bolkainy, M., Mokhtar, N. & Ghoneim, M. (1981) The impact of schistosomiasis on the pathology of bladder carcinoma. Cancer Research 48, 2643–2648.Google ScholarPubMed
EI-Muelhi, M. & Mansour, M. (1990) Hepatic drug conjuga tion and deconjugation systems in hepatosplenic schistosomiasis. Biochemical Pharmacology 40, 1923–1925.CrossRefGoogle Scholar
Esparz, I., Rupple, A., Mestan, J. & Krammer, P.H. (1988) Preactivation of macrophages in mice acutely infected with Schistosoma mansoni. Immunobiology 177, 105–119.CrossRefGoogle Scholar
Gelboin, H.V. (1980) Benzo(a)pyrene metabolism, activation, and carcinogenesis: role and regulation of mixed-function oxidases and related enzymes. Physiological Review 60, 1107–1166.CrossRefGoogle Scholar
Gentile, J.M., Brown, S., Aardema, M., Clark, D. & Blankesspoor, H. (1985) Modified mutagen metabolism in Schistosoma haematobium-infested organisms. Archives of Environmental Health 40, 5–12.CrossRefGoogle Scholar
Gooderham, N.J. & Mannering, G.J. (1985) Depression of the hepatic cytochrome P450 monooxygenase system by treatment of mice with the anti-neoplastic agents 5-azacytidine. Cancer Research 45, 1569–1572.Google Scholar
Gopalan, P., Jensen, D. & Lotlikar, P. (1992) Glutathione conjugation of microsomes-mediated and synthetic aflatoxin B1-8,9-oxide by purified glutathione S-transferases from rats. Cancer Letters 64, 225–233.CrossRefGoogle Scholar
Gopalan, P., Hirumn, S. & Lotlikar, P. (1994) Effect of glutathione levels on aflatoxin B1-DNA binding in livers and kidney of male rats and hamsters pretreated with buthionine sulfoximine and diethylmaleate. Cancer Let ters 76, 25–30.CrossRefGoogle Scholar
Griffin, D.W. (1982) Mechanism of action, metabolism, and toxicity of buthionine sulfoximine and its higher homo logies, potent inhibitors of glutathione synthesis. Journal of Biological Chemistry 257, 13704–13712.CrossRefGoogle Scholar
Guengerich, E.P. (1988) Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy. Cancer Research 48, 2946–2954.Google ScholarPubMed
Guengerich, F.P. (1991) Reactions and significance of cytochrome P-450. Journal of Biological Chemistry 226, 10019–10022.CrossRefGoogle Scholar
Habib, S.L., Sheweita, S.A., Awad, A., Mashaal, N., Soliman, A. & Mostafa, M.H. (1996) Influence of Schistosoma mansoni infection on carcinogen-metabolizing capacities and in vitro aflatoxin B1 metabolism in human liver. Oncology Reports 3, 769–773.Google ScholarPubMed
Habig, W., Pabst, M. & Jakoby, W. (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry 249, 7130–7139.CrossRefGoogle ScholarPubMed
Hamilton, T.C., Winker, M.A. & Lovie, K.G. (1985) Augmentation of adriamycin, mephalan, and cisplatin cytotoxicity in drug-resistant and sensitive human ovarian carcinoma cell lines by buthionine sulfoximine, mediated glutathione depletion. Biochemical Pharmacology 34, 2583–2589.CrossRefGoogle Scholar
Hasler, J.A., Siwela, A.H., Nyathi, C.B. & Chetsanga, C.J. (1986) The effect of schistosomiasis on the activation of aflatoxin B1. Research Communications in Pathology and Pharmacology 51, 421–423.Google ScholarPubMed
Howie, A.F., Forrester, L.M., Glancey, M.J. et al. (1990) Glutathione S-transferase and glutathione peroxidase expression in normal and tumor human tissues. Carcino genesis 11, 451–458.CrossRefGoogle Scholar
Jakoby, W.B. & Habig, W.H. (1980) Glutathione transferases. pp. 63–94in Jakoby, W.B. (Ed.) Enzymatic basis of detoxification. New York, Academic Press.CrossRefGoogle Scholar
James, N., Gay, R. & Hilf, R. (1980) Influence of estrogen on glutathione levels and glutathione-metabolizing enzymes in uteri and R3230 AC mammary tumors of rats. Biochimica et Biophysica Acta 630, 485–496.Google Scholar
Ketterer, B. (1988) Protective role of glutathione and glutathione S-transferases in mutagenesis and carcino genesis. Mutation Research 202, 343–361.CrossRefGoogle Scholar
Kim, S.Y., Chung, J.H., Kang, K.W., Joe, C.O. & Park, K.H. (1992) Relationship between activities of cytochrome P-450 monooxygenase in human placental microsomes and binding of benzo(a)pyrene metabolism to calf thymus DNA. Drug and Chemical Toxicology 15, 313–327.CrossRefGoogle ScholarPubMed
Lawson, J. & Wilson, R. (1980) Metabolic changes associated with the migration of the schistosomula of Schistosoma mansoni in the mammal host. Parasitology 81, 325–336.CrossRefGoogle ScholarPubMed
Lotlikar, P., Insetta, S. & Lyons, P. (1980) Inhibition of microsomes mediated binding of aflatoxin B1 to DNA by glutathione S-transferase. Cancer Letters 9, 143–149.CrossRefGoogle ScholarPubMed
Lowry, O.H., Rosbrough, N.J., Farr, A.L. & Randall, R.J. (1951) Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193, 265–275.CrossRefGoogle ScholarPubMed
Malaveill, C., Brun, G. & Bartsch, H. (1980) Effect of glutathione and uridine 5'-diphosphoglucuronic acid and mutagenesis by benzo(a)pyrene and aflatoxin B1 in the Salmonella/microsome assay. Mutation Research 83, 15–24.CrossRefGoogle Scholar
Miller, E.C. & Miller, J.A. (1976) The metabolism of chemical carcinogens to reactive electrophiles and their possible mechanism of action in carcinogenesis. pp. 737–762 in Searle, C.S. (Ed.) Chemical carcinogens. Washington DC, The American Chemical Society.Google Scholar
Mitchell, J., Jollow, D. & Potter, W. (1973) Acetaminophen induced hepatic necroses IV. Protective role of glutathione. Journal of Pharmacology and Experimental Therapeutics 187, 211–227.Google ScholarPubMed
Miwa, G.T., West, S.B., Huang, M. & Lu, A.Y. (1979) Studies on the association of cytochrome P450 and NADPH-cytochrome C reductase during catalysis in a reconstituted hydroxylating system. Journal of Biological Chemistry 254, 5695–5700.CrossRefGoogle Scholar
Miwa, M., Stueher, D.J., Marlette, M.A., Wishnok, J.S. & Tannenbaum, S. (1987) N-nitrosamine formation by macrophages. pp. 340–344in Bartsch, H., O'Neill, I.K. & Schulte-Hermann, R.C. (Eds) Relevance of N-nit roso compounds to human cancer: exposure and mechanisms. IARC Scientific Publication no. 84.Google Scholar
Mostafa, M., Helmi, S., Badawi, A., Tricker, A.R., Spiegelhoder, B. & Preussman, R. (1994) Nitrate, nitrite and volatile N-nitroso compounds in the urine of Schistosoma haematobium and Schistosoma mansoni infected patients. Carcinogenesis 15, 619–625.CrossRefGoogle ScholarPubMed
Mostafa, M.H., Sheweita, S.A. & Abdel-Moneam, N. (1990) Influence of some anti-inflammatory drugs on the activity of aryl hydrocarbon hydroxylase and the cytochrome P-450 content. Environmental Research 52, 77–82.CrossRefGoogle Scholar
Mostafa, M.H., El-bassiouni, E.A., El-Sewedy, S.M., Akhnouk, S., Tawific, T. & Abel-Rafee, A. (1984) Hepatic microsomal enzymes in Schistosoma mansoni infected mice. I. Effect of duration of infection and lindane administration on dimethylnitrosamine deme thylase. Environmental Research 35, 154–159.CrossRefGoogle Scholar
Mostafa, M.H., Sheweita, S.A., El-Kowedy, A. & Badawi, A.E. (1993) Alterations in the carcinogen metabolizing capacities of mouse liver during Schistosoma mansoni infection. International Journal of Oncology 2, 695–699.CrossRefGoogle ScholarPubMed
Olivier, L. & Stirewalt, M.A. (1952) An efficient methods for exposure of mice to cercariae of Schistosoma mansoni. Journal of Parasitology 38, 19–23.CrossRefGoogle ScholarPubMed
Omura, T. & Sato, R. (1964) The carbon monoxide-binding pigments of liver microsomes. II. Solubilization, purifica tion and properties. Journal of Biological Chemistry 239, 2379–2385.CrossRefGoogle Scholar
Pegg, A.E. (1983) Alkylation and subsequent repair of DNA after exposure to dimethylnitrosamine and related compounds. pp. 83–133in Hodgson, E., Bend, J.B. & Philpot, R.M. (Eds) Reviews in biochemical toxicology. New York, Elsevier.Google Scholar
Rossi, L., Moore, G.A., Orrenius, S. & O'Brien, P.J. (1988) Quinone toxicity in hepatocytes without oxidative stress. Archives of Biochemistry and Biophysics 251, 25–35.CrossRefGoogle Scholar
Sato, K. (1989) Glutathione transferases as markers of preneoplasia and neoplasia. Advanced Cancer Research 52,205–255.CrossRefGoogle ScholarPubMed
Schiller, E.L. & Haese, W.H. (1973) Histologic process of healing in hepatic injury due to eggs of S. mansoni in mice following curative chemotherapy. American Journal of Tropical Medicine and Hygiene 22, 211–214.CrossRefGoogle Scholar
Schwartz, D. (1984) Carcinoma of the uterine cervix and schistosomiasis in West Africa. Gynecology Oncology 19, 365–370.CrossRefGoogle ScholarPubMed
Seelig, G.F. & Meister, A. (1985) Glutathione biosynthesis; γ-glutamylcysteine synthetase from rat kidney. Methods in Enzymology 113, 379–390.CrossRefGoogle ScholarPubMed
Sexton, D.J. & Mutus, B. (1992) Glutathione reductases from a variety of sources are inhibited by physiological levels of glutathione. Comparative Biochemistry and Physiology 103B, 897–901.Google Scholar
Shea, T.C., Kelley, S.L. & Henner, W.D. (1988) Identification of an anionic form of glutathione transferase present in many human tumors and human tumor cell lines. Cancer Research 48, 527–533.Google ScholarPubMed
Sherif, M., El-Mawla, N. & El-Bolkainy, N. (1975) Clinical staging of malignant in patients suspected to have hepatosplenic schistosomiasis. Journal of Tropical Medicine and Hygiene 78, 67–70.Google Scholar
Sheweita, S.A. & Mostafa, M.H. (1995) Recovery of the hepatic carcinogen-metabolizing capacity in schistosome infected mice after treatment with the antischistosomal praziquantel. Oncology Reports 2, 155–159.Google ScholarPubMed
Sheweita, S.A. & Mostafa, M.H. (1996a) N-nitrosamines and their effects on the hepatic level of glutathione and glutathione reductase and glutathione 5-transferase activities in the liver of male mice. Cancer Letters 99,29–34.CrossRefGoogle Scholar
Sheweita, S.A. & Mostafa, M.H. (1996b) N-nitroso com pounds induce changes in carcinogen-metabolizing enzymes. Cancer Letters 106, 243–249.CrossRefGoogle Scholar
Siwela, A.H., Nyathi, C.B., Chetsanga, C.J. & Hasler, J.A. (1990) The effect of schistosomiasis on the covalent binding of 2-acetylaminofluorene to mouse liver macro molecules in vivo and in vitro. Biochemical Pharmacology 40, 379–382.CrossRefGoogle Scholar
Stohs, S.J., Groftstrom, R.C., Burke, M.D. & Orrenius, S. (1976) Xenobiotic metabolism and enzyme induction in isolated intestinal microsomes. Drug Metabolism and Disposition 4, 517–521.Google ScholarPubMed
Thompson, T., Watkins, J. & Gergus, Z. (1982) Effect of microsomal enzyme inducers on the soluble enzymes of hepatic phase II biotransformation. Toxicology and Applied Pharmacology 66, 400–408.CrossRefGoogle ScholarPubMed
Tricker, A.R., Mostafa, M.H., Spiegelhalder, B. & Preussman, R. (1989) Urinary excretion of nitrate, nitrite and N nitroso compounds in schistosomiasis and bilharzial bladder cancer patients. Carcinogenesis 10, 547–552.CrossRefGoogle Scholar
Trush, M.A., Twerdok, L.E. & Esterline, R.I. (1990) Comparison of oxidant activities and the activation of benzo(a)pyrene-7,8-dihydrodiol by polymorphonuclear leukocytes from human, rat and mouse. Xenobiotica 20, 925–932.CrossRefGoogle ScholarPubMed
Weibel, F.J. & Gelboin, H.V. (1975) Arylhydrocarbon (benzo(a)pyrene) hydroxylase in liver from rats of different age, sex and nutritional status. Biochemical Pharmacology 24, 1511–1515.CrossRefGoogle Scholar
Williams, C.H. & Kamin, H. (1962) Microsomal triphospho pyridine nucleotide cytochrome C reductase of liver. Journal of Biological Chemistry 237, 587–595.CrossRefGoogle Scholar
World Health Organization (1985) The control of schistoso masis. Report of a WHO Expert Committee, WHO, Geneva, Technical Report Series No. 728.Google Scholar
Yang, C.S., Patten, C., Lee, M.J., Li, M., Yoo, J.S., Pan, J. & Hong, J. (1987) Enzymatic mechanisms in the metabolic activation of N-nitrosodialkylamine. pp. 104–108in Bartsch, H., O'Neil, I.K. & Schultehermann, R. (Eds) The relevance of N-nitroso compounds to human cancer: exposure and mechanisms. Lyon, Sci. Pub.Google Scholar
Young, N.C. (1987) Inducibility of the hepatic drug-metabo lizing capacity of mice infected with Schistosoma mansoni. American Journal of Tropical Medicine and Hygiene 27, 1181– 1191.Google Scholar