Inhibition of doxorubicin-induced liver toxicity by a new dihydroquinoline type antioxidant.
The influence of a new dihydroquinoline type antioxidant on doxorubicin-induced hepatic toxicity was studied in mice (CFLP, LATI). Four groups of mice were studied: control, doxorubicin-treated, 5,6-methylen-bis (2,2,4/-trimethyl-1,2-dihydroquinoline/-disulphate (MDS)-treated, as well as doxorubicin and MDS-treated groups. Doxorubicin (15 mg/kg) was administered intraperitoneally, the MDS solution was given by a gastric tube. Liver function was assessed by the serum glutaminic-oxaloacetic-transaminase (SGOT) reaction. The lipid peroxidation in liver tissue was determined by the rate of malondialdehyd (MDA) production, the permeability of the liver lysosomal membrane was established by measuring beta-glucuronidase activity and its release from the cells. The MDS treatment proved to be effective in significantly reducing SGOT elevation, MDA production and lysosomal membrane damage in hepatic tissue. Clinical trials seem to be justified in using antioxidative substances to control doxorubicin toxicity.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004317:Doxorubicin / Q000633:toxicity*; D005966:Glucuronidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011804:Quinolines / Q000494:pharmacology*
D000975:Antioxidants; D011804:Quinolines; D008315:Malondialdehyde; D004317:Doxorubicin; C044964:6,6'-methylenebis(2,2-dimethyl-4-methanesulfonic acid-1,2-dihydroquinoline); D001219:Aspartate Aminotransferases; D005966:Glucuronidase