Skip to main content

Indomethacin induced hepatic alterations in mono-oxygenase system and faecal clostridium perfringens enterotoxin in the rat

Agents and Actions volume 31, pages 313–316 (1990)Cite this article

Abstract

The administration of indomethacin to rats, at the dose of 10 mg/kg once daily for three days, caused a loss of microsomal cytochrome P-450 and cytochrome b5 in the liver, and a fall in drug-metabolizing enzyme activities (i.e. aminopyrine N-demethylase, NADP cyt. c. reductase). Indomethacin also induced intestinal lesions and a significant increase in Clostridium perfringens enterotoxin levels in the feces at 24 hours after both the second and third day of treatment.

The above findings suggest that the development of intestinal lesion and the accompanying release of Clostridium perfringens enterotoxin, as well as hepatic enzyme alterations in the rat, result from indomethacin administration.

Some of the data in this paper were presented at the Meeting of British Pharmacological Society in Ireland, July 6th–8th, 1988.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. M. A. Patmas, S. L. Wilborn and S. W. Shankel,Acute multisystem toxicity associated with the use of nonsteroidal antiinflammatory drugs. Arch. Intern. Med.144, 519–521 (1984).

    Article  PubMed  Google Scholar 

  2. M. D. Burke, M. Falzon and A. S. Milton,Decreased hepatic microsomal cytochrome P-450 due to indomethacin: protective roles of 16,16 dimethyl prostaglandin F 2 and inducing agents. Biochem. Pharmacology32, 389–397 (1983).

    Article  Google Scholar 

  3. M. E. Fracasso, L. Cuzzolin, P. Del Soldato, R. Leone, G. P. Velo and G. Benoni,Multisystem toxicity of indomethacin: effects on kidney, liver and intestine in the rat. Agents and Actions22, 310–313 (1987).

    PubMed  Google Scholar 

  4. B. A. Bartholomew and M. F. Stringer,Clostridium perfringens enterotoxin: a brief review. Biochemical Society Transactions12, 195–197 (1985).

    Google Scholar 

  5. L. Niilo,Mechanism of action of the enteropathogenic factor of Clostridium perfringens type A. Infect. Immu.3, 100–106 (1971).

    Google Scholar 

  6. V. Weissenborn, S. Maedge, D. Buettner and K. F. Sewing,Indomethacin-induced gastrointestinal lesions in relations to tissue concentration, food intake and bacterial invasion in the rat. Pharmacology30, 32–39 (1985).

    PubMed  Google Scholar 

  7. H. D. Lowry, M. J. Rosenbrough, A. L. Farr and R. Randall,Protein measurement with the Folin phenol reagent. J. Biol. Chem.193, 265–275 (1951).

    PubMed  Google Scholar 

  8. T. Omura and R. Sato,The carbon monoxide binding pigment of liver microsomes. J. Biol. Chem.239, 2370–2378 (1964).

    PubMed  Google Scholar 

  9. M. Delaforge, M. Jaouen and D. Mansuy,Dual effects of macrolide antibiotics on rat liver cytochrome P-450. Biochem. Pharmacol.32, 2309–2318 (1983).

    Article  PubMed  Google Scholar 

  10. A. V. Phillips and R. G. Langdon,Hepatic triphosphopyridine nucleotide-cytochrome c reductase: isolation, characterization and kinetic studies. J. Biol. Chem.237, 2652–2660 (1962).

    PubMed  Google Scholar 

  11. J. Werringloer, InMethods in Enzymology. Vol. 52 (Eds. S. Fleisher and L. Parker) pp. 297–302. Academic Press, New York 1978.

    Google Scholar 

  12. G. Sakaguchi, T. Uemura and H. P. Riemann,Simplified method for purification of Clostridium perfringens type A enterotoxin. Appl. Microbiol.26, 762–767 (1973).

    PubMed  Google Scholar 

  13. M. Falzon, A. S. Milton and M. D. Burke,Are the decrease in hepatic cyt. P-450 and other drug-metabolizing enzymes caused by indomethacin in vivo mediated by intestinal bacterial endotoxins? Biochem. Pharmac.33, 1285–1292 (1984).

    Article  Google Scholar 

  14. F. A. Fitzpatrick and R. C. Murphy,Cyt. P-450 metabolism of arachidonic acid: formation and biological actions of epoxygenase-derivated eicosanois. Pharm. Rev.40, 229–241 (1989).

    Google Scholar 

Download references

Author information

Affiliations

  1. Institute of Pharmacology, University of Verona, Policlinico Borgo Roma, 37134, Verona, Italy

    M. E. Fracasso, R. Leone, L. Cuzzolin, G. P. Velo & G. Benoni

  2. Laboratory of Research, Italfarmaco S.p.A., Policlinico Borgo Roma, 37134, Milan, Italy

    P. Del Soldato

Authors
  1. M. E. Fracasso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Leone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Cuzzolin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Del Soldato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. P. Velo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Benoni
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fracasso, M.E., Leone, R., Cuzzolin, L. et al. Indomethacin induced hepatic alterations in mono-oxygenase system and faecal clostridium perfringens enterotoxin in the rat. Agents and Actions 31, 313–316 (1990). https://doi.org/10.1007/BF01997625

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01997625

Keywords

  • Enzyme Activity
  • Indomethacin
  • NADP
  • Hepatic Enzyme
  • Clostridium Perfringens