Liver response to indomethacin-induced intestinal injury.
The aim of our study was to evaluate the impact of impaired barrier function of the small intestine induced by indomethacin on biochemical markers of liver damage (serum levels of alanine aminotransferase, aspartate aminotransferase, bilirubin), and liver functional parameters (serum concentration of albumin, liver DNA synthesis). Indomethacin (Sigma) was administered in 2 injections in a dose of 7.5 mg/kg subcutaneously spaced 24 hours apart, rats were sacrificed 24, 48 or 72 hours after the second dose of indomethacin. Control rats received indomethacin vehicle (5% NaHCO3, pH 7.4, 1.0 ml/kg) in the same manner. Small intestine injury was approved by increased permeability (measured as a lactulose-mannitol index). Significant increase of small intestine DNA synthesis (estimated by incorporation of 3H thymidine) in indomethacin-treated rats 48 (p < 0.01) and 72 (p < 0.05) hours after the second dose of indomethacin documents induction of reparative process. All biochemical markers of liver injury were significantly decreased in indomethacin treated rats in all recorded intervals (p < 0.05). By contraries, serum concentration of albumin, which predicates about liver function, was in indomethacin-treated rats significantly decreased in all intervals (p < 0.01). To explain these contrarious results of indomethacin-induced impaired barrier function of the small intestine on the liver deserves further studies.
Cervinková
Zuzana
Z
Department of Physiology, Charles University, Prague, Faculty of Medicine, Hradec Králové. wolff@lfhk.cuni.cz
Radvaková
Dagmar
D
Kohout
Pavel
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D007213:Indomethacin / Q000633:toxicity*; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D007792:Lactulose; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008353:Mannitol; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008353:Mannitol; D007792:Lactulose; D007213:Indomethacin