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. 1986 Nov 1;239(3):785–788. doi: 10.1042/bj2390785

Strain differences in the maintenance of cytochrome P-450 and mixed-function-oxidase activities in cultured rat hepatocytes. Effect of prostaglandins.

M H Grant, S J Smith, M D Burke
PMCID: PMC1147357  PMID: 3103607

Abstract

The mixed-function-oxidase (MFO) activities, ethoxyresorufin and pentoxyphenoxazone O-dealkylase, of cultured Hooded-Lister(HL)-rat hepatocytes declined rapidly during 72 h of culture, whereas in Sprague-Dawley(SD)-rat hepatocytes the MFO activities increased between 24 and 72 h in culture. Cytochrome P-450 content declined at the same rate in both HL- and SD-rat hepatocyte cultures. NADPH:cytochrome c reductase and NADH:cytochrome b5 reductase were more stable in SD- than in HL-rat hepatocyte cultures. 16,16-Dimethylprostaglandins E2 and F2 alpha improved the maintenance of cytochrome P-450 content, MFO activity and NADPH:cytochrome c reductase in the HL-rat hepatocyte cultures. In SD-rat hepatocytes, the prostaglandins had no effect on cytochrome P-450 content or NADPH:cytochrome c reductase activity, whereas they prevented the increase observed in MFO activities between 24 and 72 h after culture.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burke M. D., Mayer R. T. Differential effects of phenobarbitone and 3-methylcholanthrene induction on the hepatic microsomal metabolism and cytochrome P-450-binding of phenoxazone and a homologous series of its n-alkyl ethers (alkoxyresorufins). Chem Biol Interact. 1983 Jul 15;45(2):243–258. doi: 10.1016/0009-2797(83)90072-8. [DOI] [PubMed] [Google Scholar]
  2. Burke M. D., Thompson S., Elcombe C. R., Halpert J., Haaparanta T., Mayer R. T. Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues: a series of substrates to distinguish between different induced cytochromes P-450. Biochem Pharmacol. 1985 Sep 15;34(18):3337–3345. doi: 10.1016/0006-2952(85)90355-7. [DOI] [PubMed] [Google Scholar]
  3. Dickins M., Peterson R. E. Effects of a hormone-supplemented medium on cytochrome P-450 content and mono-oxygenase activities of rat hepatocytes in primary culture. Biochem Pharmacol. 1980 May 1;29(9):1231–1238. doi: 10.1016/0006-2952(80)90279-8. [DOI] [PubMed] [Google Scholar]
  4. Falzon M., Milton A. S., Burke M. D. Are the decreases in hepatic cytochrome P-450 and other drug-metabolising enzymes caused by indomethacin in vivo mediated by intestinal bacterial endotoxins? 16,16-Dimethylprostaglandin F2 alpha prevents decreases in hepatic drug-metabolising enzymes due to exogenous endotoxin. Biochem Pharmacol. 1984 Apr 15;33(8):1285–1292. doi: 10.1016/0006-2952(84)90182-5. [DOI] [PubMed] [Google Scholar]
  5. Funck-Brentano C., Tinel M., Degott C., Letteron P., Babany G., Pessayre D. Protective effect of 16,16-dimethyl prostaglandin E2 on the hepatotoxicity of bromobenzene in mice. Biochem Pharmacol. 1984 Jan 1;33(1):89–96. doi: 10.1016/0006-2952(84)90374-5. [DOI] [PubMed] [Google Scholar]
  6. Grant M. H., Hawksworth G. M. The activity of UDP-glucuronyltransferase, sulphotransferase and glutathione-S-transferase in primary cultures of rat hepatocytes. Biochem Pharmacol. 1986 Sep 1;35(17):2979–2982. doi: 10.1016/0006-2952(86)90498-3. [DOI] [PubMed] [Google Scholar]
  7. Grant M. H., Melvin M. A., Shaw P., Melvin W. T., Burke M. D. Studies on the maintenance of cytochromes P-450 and b5, monooxygenases and cytochrome reductases in primary cultures of rat hepatocytes. FEBS Lett. 1985 Oct 7;190(1):99–103. doi: 10.1016/0014-5793(85)80436-1. [DOI] [PubMed] [Google Scholar]
  8. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  9. Lake B. G., Paine A. J. The effect of hepatocyte culture conditions on cytochrome P-450 linked drug metabolising enzymes. Biochem Pharmacol. 1982 Jun 1;31(11):2141–2144. doi: 10.1016/0006-2952(82)90438-5. [DOI] [PubMed] [Google Scholar]
  10. Maslansky C. J., Williams G. M. Primary cultures and the levels of cytochrome P450 in hepatocytes from mouse, rat, hamster, and rabbit liver. In Vitro. 1982 Aug;18(8):683–693. doi: 10.1007/BF02796423. [DOI] [PubMed] [Google Scholar]
  11. Moldéus P., Högberg J., Orrenius S. Isolation and use of liver cells. Methods Enzymol. 1978;52:60–71. doi: 10.1016/s0076-6879(78)52006-5. [DOI] [PubMed] [Google Scholar]
  12. Morrison H., Hammarskiöld V., Jernström B. Status of reduced glutathione in primary cultures of rat hepatocytes and the effect on conjugation of benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide. Chem Biol Interact. 1983 Jul 15;45(2):235–242. doi: 10.1016/0009-2797(83)90071-6. [DOI] [PubMed] [Google Scholar]
  13. OMURA T., SATO R. THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. II. SOLUBILIZATION, PURIFICATION, AND PROPERTIES. J Biol Chem. 1964 Jul;239:2379–2385. [PubMed] [Google Scholar]
  14. Robert A. Current history of cytoprotection. Prostaglandins. 1981;21 (Suppl):89–96. doi: 10.1016/0090-6980(81)90123-4. [DOI] [PubMed] [Google Scholar]
  15. Sirica A. E., Pitot H. C. Drug metabolism and effects of carcinogens in cultured hepatic cells. Pharmacol Rev. 1979 Sep;31(3):205–228. [PubMed] [Google Scholar]
  16. Stachura J., Tarnawski A., Ivey K. J., Mach T., Bogdal J., Szczudrawa J., klimczyk B. Prostaglandin protection of carbon tetrachloride-induced liver cell necrosis in the rat. Gastroenterology. 1981 Aug;81(2):211–217. [PubMed] [Google Scholar]
  17. Steward A. R., Dannan G. A., Guzelian P. S., Guengerich F. P. Changes in the concentration of seven forms of cytochrome P-450 in primary cultures of adult rat hepatocytes. Mol Pharmacol. 1985 Jan;27(1):125–132. [PubMed] [Google Scholar]
  18. Williams G. M., Laspia M. F., Dunkel V. C. Reliability of the hepatocyte primary culture/DNA repair test in testing of coded carcinogens and noncarcinogens. Mutat Res. 1982 Oct;97(5):359–370. doi: 10.1016/0165-1161(82)90003-6. [DOI] [PubMed] [Google Scholar]

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