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. 1974 May 1;61(2):344–358. doi: 10.1083/jcb.61.2.344

NAFENOPIN-INDUCED HEPATIC MICROBODY (PEROXISOME) PROLIFERATION AND CATALASE SYNTHESIS IN RATS AND MICE

Absence of Sex Difference in Response

Jarnardan K Reddy 1, Daniel L Azarnoff 1, Donald J Svoboda 1, Jada D Prasad 1
PMCID: PMC2109285  PMID: 4208071

Abstract

Nafenopin (2-methyl-2[p-(1,2,3,4-tetrahydro-1-naphthyl)phenoxy]-propionic acid; Su-13437), a potent hypolipidemic compound, was administered in varying concentrations in ground Purina Chow to male and female rats, wild type (Csa strain) mice and acatalasemic (Csb strain) mice to determine the hepatic microbody proliferative and catalase-inducing effects. In all groups of animals, administration of nafenopin at dietary levels of 0.125% and 0.25% produced a significant and sustained increase in the number of peroxisomes. The hepatic microbody proliferation in both male and female rats and wild type Csa strain mice treated with nafenopin was of the same magnitude and was associated with a two-fold increase in catalase activity and in the concentration of catalase protein. The increase in microbody population in acatalasemic mice, although not accompanied by increase in catalase activity, was associated with a twofold increase in the amount of catalase protein. The absence of sex difference in microbody proliferative response in nafenopin-treated rats and wild type mice is of particular significance, since ethyl-α-p-chlorophenoxyisobutyrate (CPIB)-induced microbody proliferation and increase in catalase activity occurred only in males. Nafenopin can, therefore, be used as an inducer of microbody proliferation and of catalase synthesis in both sexes of rats and mice. The serum glycerol-glycerides were markedly lowered in all the animals given nafenopin, which paralleled the increase in liver catalase. All the above effects of nafenopin were fully reversed when the drug was withdrawn from the diet of male rats. During reversal, several microbody nucleoids were seen free in the hyaloplasm or in the dilated endoplasmic reticulum channels resulting from a rapid reduction in microbody matrix proteins after the withdrawal of nafenopin from the diet. Because of microbody proliferation and catalase induction with increasing number of hypolipidemic compounds, additional studies are necessary to determine the interrelationships of microbody proliferation, catalase induction, and hypolipidemia.

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Selected References

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  1. Aebi H., Suter H., Feinstein R. N. Activity and stability of catalase in blood and tissues of normal and acatalasemic mice. Biochem Genet. 1968 Nov;2(3):245–251. doi: 10.1007/BF01474764. [DOI] [PubMed] [Google Scholar]
  2. Azarnoff D. L., Svoboda D. J. Microbodies in experimentally altered cells. VI. Thyroxine displacement from plasma proteins and clofibrate effect. Arch Int Pharmacodyn Ther. 1969 Oct;181(2):386–393. [PubMed] [Google Scholar]
  3. BERNHARD W., ROUILLER C. Microbodies and the problem of mitochondrial regeneration in liver cells. J Biophys Biochem Cytol. 1956 Jul 25;2(4 Suppl):355–360. doi: 10.1083/jcb.2.4.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BEST M. M., DUNCAN C. H. HYPOLIPEMIA AND HEPATOMEGALY FROM ETHYL CHLOROPHENOXYISOBUTYRATE (CPIB) IN THE RAT. J Lab Clin Med. 1964 Oct;64:634–642. [PubMed] [Google Scholar]
  5. Beckett R. B., Weiss R., Stitzel R. E., Cenedella R. J. Studies on the hepatomegaly caused by the hypolipidemic drugs nafenopin and clofibrate. Toxicol Appl Pharmacol. 1972 Sep;23(1):42–53. doi: 10.1016/0041-008x(72)90202-5. [DOI] [PubMed] [Google Scholar]
  6. Best M. M., Duncan C. H. Lipid effects of a phenolic ether (Su-13437) in the rat: comparison with CPIB. Atherosclerosis. 1970 Sep-Oct;12(2):185–192. doi: 10.1016/0021-9150(70)90095-x. [DOI] [PubMed] [Google Scholar]
  7. Caravaca J., Dimond E. G., Sommers S. C., Wenk R. Prevention of induced atherosclerosis by peroxidase. Science. 1967 Mar 10;155(3767):1284–1287. doi: 10.1126/science.155.3767.1284. [DOI] [PubMed] [Google Scholar]
  8. Conney A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967 Sep;19(3):317–366. [PubMed] [Google Scholar]
  9. Cuadrado R. R., Bricker L. A. An abnormality of hepatic lipogenesis in a mutant strain of acatalasemic mice. Biochim Biophys Acta. 1973 May 24;306(2):168–172. doi: 10.1016/0005-2760(73)90222-1. [DOI] [PubMed] [Google Scholar]
  10. De Duve C., Baudhuin P. Peroxisomes (microbodies and related particles). Physiol Rev. 1966 Apr;46(2):323–357. doi: 10.1152/physrev.1966.46.2.323. [DOI] [PubMed] [Google Scholar]
  11. De Duve C. Evolution of the peroxisome. Ann N Y Acad Sci. 1969 Dec 19;168(2):369–381. doi: 10.1111/j.1749-6632.1969.tb43124.x. [DOI] [PubMed] [Google Scholar]
  12. Fahimi H. D. Cytochemical localization of peroxidatic activity of catalase in rat hepatic microbodies (peroxisomes). J Cell Biol. 1969 Nov;43(2):275–288. doi: 10.1083/jcb.43.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ganschow R. E., Schimke R. T. Independent genetic control of the catalytic activity and the rate of degradation of catalase in mice. J Biol Chem. 1969 Sep 10;244(17):4649–4658. [PubMed] [Google Scholar]
  14. HOCHSTEIN P., ERNSTER L. ADP-ACTIVATED LIPID PEROXIDATION COUPLED TO THE TPNH OXIDASE SYSTEM OF MICROSOMES. Biochem Biophys Res Commun. 1963 Aug 14;12:388–394. doi: 10.1016/0006-291x(63)90111-6. [DOI] [PubMed] [Google Scholar]
  15. Hess R., Bencze W. L. Hypolipidaemic properties of a new tetralin derivative (CIBA 13,437-Su). Experientia. 1968 May 15;24(5):418–419. doi: 10.1007/BF02144360. [DOI] [PubMed] [Google Scholar]
  16. Hruban Z., Swift H., Slesers A. Ultrastructural alterations of hepatic microbodies. Lab Invest. 1966 Dec;15(12):1884–1901. [PubMed] [Google Scholar]
  17. Hruban Z., Vigil E. L., Slesers A., Hopkins E. Microbodies: constituent organelles of animal cells. Lab Invest. 1972 Aug;27(2):184–191. [PubMed] [Google Scholar]
  18. KAMPSCHMIDT R. F. MECHANISM OF LIVER CATALASE DEPRESSION IN TUMOR-BEARING ANIMALS: A REVIEW. Cancer Res. 1965 Jan;25:34–45. [PubMed] [Google Scholar]
  19. Kinoshita F. K., DuBois K. P. Induction of hepatic microsomal enzymes by herban, diuron, and other substituted urea herbicides. Toxicol Appl Pharmacol. 1970 Sep;17(2):406–417. doi: 10.1016/0041-008x(70)90198-5. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Leighton F., Poole B., Lazarow P. B., De Duve C. The synthesis and turnover of rat liver peroxisomes. I. Fractionation of peroxisome proteins. J Cell Biol. 1969 May;41(2):521–535. doi: 10.1083/jcb.41.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Novikoff A. B., Novikoff P. M., Davis C., Quintana N. Studies on microperoxisomes. V. Are microperoxisomes ubiquitous in mammalian cells? J Histochem Cytochem. 1973 Aug;21(8):737–755. doi: 10.1177/21.8.737. [DOI] [PubMed] [Google Scholar]
  23. OLIVER M. F. FURTHER OBSERVATIONS ON THE EFFECTS OF ATROMID AND OF ETHYL CHLOROPHENOXYISOBUTYRATE ON SERUM LIPID LEVELS. J Atheroscler Res. 1963 Sep-Dec;3:427–444. doi: 10.1016/s0368-1319(63)80023-x. [DOI] [PubMed] [Google Scholar]
  24. Reddy J., Bunyaratvej S., Svoboda D. Microbodies in experimentally altered cells. IV. Acatalasemic (CSb) mice treated with CPIB. J Cell Biol. 1969 Aug;42(2):587–596. doi: 10.1083/jcb.42.2.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Reddy J., Bunyaratvej S., Svoboda D. Microbodies in experimentally altered cells. V. Histochemical and cytochemical studies on the livers of rats and acatalasemic (Csb) mice treated with CPIB. Am J Pathol. 1969 Sep;56(3):351–370. [PMC free article] [PubMed] [Google Scholar]
  26. Reddy J., Chiga M., Bunyaratvej S., Svoboda D. Microbodies in experimentally altered cells. VII. CPID-induced hepatic microbody proliferation in the absence of significant catalase synthesis. J Cell Biol. 1970 Jan;44(1):226–234. doi: 10.1083/jcb.44.1.226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Reddy J., Chiga M., Svoboda D. Stimulation of liver catalase synthesis in rats by ethyl-alpha-p-chlorophenoxyisobutyrate. Biochem Biophys Res Commun. 1971 Apr 16;43(2):318–324. doi: 10.1016/0006-291x(71)90755-8. [DOI] [PubMed] [Google Scholar]
  28. Reddy J., Svoboda D., Azarnoff D. Microbody proliferation in liver induced by nafenopin, a new hypolipidemic drug: comparison with CPIB. Biochem Biophys Res Commun. 1973 May 15;52(2):537–543. doi: 10.1016/0006-291x(73)90745-6. [DOI] [PubMed] [Google Scholar]
  29. Svoboda D., Grady H., Azarnoff D. Microbodies in experimentally altered cells. J Cell Biol. 1967 Oct;35(1):127–152. doi: 10.1083/jcb.35.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Svoboda D., Reddy J. Microbodies in experimentally altered cells. IX. The fate of microbodies. Am J Pathol. 1972 Jun;67(3):541–554. [PMC free article] [PubMed] [Google Scholar]

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