Effects of gossypol on the hepatic drug metabolizing system in rats.
Gossypol, a polyphenolic pigment found in cotton plants, has been implicated as an antifertility agent. This pigment has been shown to alter myriad metabolic pathways. The objective of this study was to determine the effect of gossypol acetic acid on the hepatic microsomal drug metabolizing enzyme system in adult female Fisher 344 rats. Subcutaneous administration in both low (15 mg/kg) and high (30 mg/kg) doses of gossypol acetic acid for five consecutive days significantly (P less than 0.00001) reduced hepatic aniline hydroxylase activity, as well as cytochrome P-450 and b5 levels. Thus, compared to the controls, the low doses of gossypol decreased the hepatic aniline hydroxylase activity and cytochrome P-450 and b5 content by 73, 54, and 43 percent, respectively. The high doses of gossypol decreased the aniline hydroxylase, cytochrome P-450, and b5 levels by 60, 51, and 46 percent, respectively, as compared to controls. These data indicate that alteration of the hepatic metabolizing system may, in part, be responsible for the secondary toxemic effects seen when gossypol is used to provide antifertility action.
Johansen
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RL
Department of Biomedical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Misra
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HP
D000815:Aniline Hydroxylase / Q000032:analysis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D015786:Cytochromes b5 / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006072:Gossypol / Q000009:adverse effects / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; D006072:Gossypol