Hepatotoxicity of gossypol in rats.
Gossypol acetic acid (GAA) at the dosage of 30 mg/kg daily for 2 weeks could prolong the sleeping time of pentobarbital, increase the SGPT level, decrease the liver concentration of cytochrome P-450 and GSH content, inhibit the activity of cytochrome C reductase and aminopyrine-N-demethylase, but was without effect on cytochrome b5 and aniline hydroxylase. At a smaller daily dosage (15 mg/kg for 4 weeks), GAA could induce the rise of SGPT level and GSH content without affecting the liver metabolizing enzymes. GAA at both dosages could induce marked pathological changes of liver cells in treated rats, such as vacuolation of mitochondria, dilation of endoplasmic reticulum and widening of perinuclear space as well as proliferation of collagen fibers in Disse's spaces. GAA could induce the formation of O2 and H2O2 and could inhibit Ca2+ sequestration in rat liver microsomes in vitro. [C14]-gossypol could bind to microsomal protein irreversibly either in the presence or absence of NADPH. It may be concluded that GAA is capable of causing damage to liver cells.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D006072:Gossypol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D008054:Lipid Peroxides / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D006072:Gossypol; C028178:gossypol acetic acid; D002118:Calcium