Gossypol is a potent inhibitor of the NAD+-dependent dehydrogenase responsible for the inactivation of prostaglandins

The effects of gossypol as inhibitor of prostaglandin 15-hydroxydehydrogenase(PGDH) were studied using several enzyme sources and a radiochemical technique. Sulphasalazine,an established PGDH inhibitor, was used as reference compound. Gossypol inhibited human placental and bovine lung PGDH dose-dependently with IC50 values of 22 and 20 microM,respectively, Inhibition was non-competitive with respect to substrate but competitive for NAD+, and favoured at pH6.6 compared to Ph9.6. In vivo his property may affect the gonadal prostaglandin system with implications for reproductive function,but caution is indicated before extrapolating this effect to the known antifertility properties of gossypol in males because the drug inhibits other NAD+-dependent dehydrogenases, notably lactate dehydrogenase isozyme X specific to spermatozoa.