Multisystem toxicity of indomethacin: effects on kidney, liver and intestine in the rat.
Some studies on the relationships among toxic effects in rat liver, kidney and intestine have been carried out. Indomethacin caused a marked reduction in microsomal enzymes, such as cytochrome P450, cytochrome b5 and aminopyrine N-demethylase in the kidney and the liver, greater in the former and for a shorter time than in the latter. Indomethacin induced intestinal lesions and marked overgrowth of intestinal bacteria, mainly of aerobic bacteria in the first 24 hours after its administration and anaerobic bacteria such as Clostridii in the second day. These findings enable us to suggest that the drug induces multisystem lesions through different mechanisms involving either a direct effect on the tissue or other microbiological or pharmacological factors.
Fracasso
M E
ME
Institute of Pharmacology, University of Verona, Italy.
Cuzzolin
L
L
Del Soldato
P
P
Leone
R
R
Velo
G P
GP
Benoni
G
G
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001420:Bacteria, Aerobic / Q000254:growth & development; D001421:Bacteria, Anaerobic / Q000254:growth & development; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004755:Enterobacteriaceae / Q000254:growth & development; D005260:Female; D007213:Indomethacin / Q000494:pharmacology / Q000633:toxicity*; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
D003573:Cytochrome b Group; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase; D007213:Indomethacin