Inhibition of 11beta-hydroxysteroid dehydrogenase in guinea pig kidney by three bioflavonoids and their interactions with gossypol.
OBJECTIVE
To study the effects of some bioflavonoids on the gossypol-induced hypokalemia.


METHODS
The 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) protein was prepared from guinea pig kidney. The activity of 11beta-OHSD with NAD as the coenzyme was measured by HPLC. The drug interaction was analysed by isobolographic method.


RESULTS
The 11beta-OHSD can be inhibited by some bioflavonoids. The IC50 (95 % confidence limits) values were: quercetin 164 (79 - 341) micromol/L, morin 913 (385 - 2173) micromol/L, and naringenin 2193 (1114 - 4315) micromol/L. When the 11beta-OHSD was treated with quercetin, tangeretin, morin, naringenin plus gossypol, the combination index (CI) values were 0.92, 0.85, 0.98, and 1.01 respectively.


CONCLUSIONS
The interaction of some bioflavonoids with gossypol might be one of the factors for gossypol-induced hypokalemia.
Wang
Mao-Shan
MS
Department of Biochemical Pharmacology, Family Planning Research Institute, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
Shi
Hong
H
Wang
Ke-Shen
KS
Reidenberg
Marcus M
MM
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D000818:Animals; D003864:Depression, Chemical; D004357:Drug Synergism; D004791:Enzyme Inhibitors; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D006072:Gossypol / Q000009:adverse effects / Q000494:pharmacology*; D006168:Guinea Pigs; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007008:Hypokalemia / Q000139:chemically induced; D008297:Male; D009243:NAD / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D047309:Flavones; D005419:Flavonoids; D009243:NAD; C008548:morin; D011794:Quercetin; D006913:Hydroxysteroid Dehydrogenases; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C059006:tangeretin; D006072:Gossypol