Reduction of apparent indicators of liver cirrhosis in rats by the arachidonate lipoxygenase inhibitor BW755C.
We have compared the effects of BW755C, a dual inhibitor of the arachidonic acid cyclo-oxygenase and lipoxygenase, with the effects of colchicine and indomethacin on the reversion of the biochemical and histochemical signs of rat liver cirrhosis. This was induced by i.p. administration of CCl4 for 11 weeks. At this point the rats were divided into four groups (10 animals each). CCl4 administration was continued for one month along with either colchicine, BW755C or indomethacin. No additional treatment was given to the control group. BW755C consistently improved all the parameters studied. Although colchicine also improved all but two markers (serum ALT activity and serum proteins) it ranked lower than BW755C in most of them. Indomethacin only modified favourably serum alkaline phosphatase activity, serum proteins, cholesterol and bilirubins and liver collagen content. The effects of BW755C could be mainly attributed to the inhibition of the lipoxygenase pathway. A common feature of colchicine, adrenal steroids and BW755C was the ability to inhibit the formation of leukotriene and other lipoxygenase products. The possibility that this property might contribute to their anti-cirrhotic actions is discussed.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D003078:Colchicine / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D003094:Collagen; D001091:Arachidonate Lipoxygenases; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D003078:Colchicine; D007213:Indomethacin