The influence of carbon tetrachloride-induced liver damage on the inflammatory reaction elicited by carrageenan and its treatment with diclofenac.
The effect of impaired hepatic function on the development of the inflammatory process as well as on treatment with diclofenac was investigated. Carbon tetrachloride was used to induce liver injury and the elevation of serum transaminases was taken as evidence for impaired hepatic function. The carrageenan-induced rat hind paw oedema and the granuloma pouch were chosen as models of inflammation. The results of the study revealed that: (1) The intensity of inflammation in both models was markedly attenuated in CCl4-treated animals. (2) Serum total proteins were decreased in liver-injured animals particularly in acute experiments. (3) In liver-injured groups diclofenac showed more pronounced anti-inflammatory activity in chronic experiments, but not in acute ones. (4) Neither CCl4 nor diclofenac affected the levels of histamine and serotonin in the granuloma pouch exudate. The level of prostaglandins was decreased in CCl4 and in diclofenac-treated animals. At the same time, the leukotriene content was elevated. The mechanism by which CCl4 induced liver injury attenuates inflammatory response to carrageenan is not entirely understood. Its effect on protein metabolism and extravasation as well as on PG synthesis could play a possible role. Decreased drug metabolism may be, at least in part, responsible for the enhanced response of diclofenac in the cases of liver-injured animals. Dose adjustment of the drug in case of hepatic impairment might be necessary.
Agha
A M
AM
Department of Pharmacology, Cairo University, Egypt.
El-Khatib
A S
AS
Kenawy
S A
SA
Khayyal
M T
MT
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D002351:Carrageenan; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000150:complications / Q000209:etiology / Q000503:physiopathology*; D004008:Diclofenac / Q000627:therapeutic use*; D005079:Excipients; D006636:Histamine Release; D007249:Inflammation / Q000145:classification / Q000188:drug therapy / Q000503:physiopathology*; D008099:Liver / Q000187:drug effects; D008297:Male; D051381:Rats; D012701:Serotonin / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D004008:Diclofenac; D012701:Serotonin; D002351:Carrageenan; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase