Synergistic effect of retinoic acid on Sn-PP mediated suppression of heme oxygenase activity in vivo in rats.

The present investigation is designed to probe the influence of excess retinoic acid (50,000 I.U.) and Sn-protoporphyrin (50 mumol/kg bw) along with retinoic acid on the activity patterns of the rate-limiting enzyme, heme oxygenase, of the heme catabolic pathway in the liver, spleen, kidney, brain, heart, and lung of male Wistar rats. Our results are noteworthy as SnPP is being used for the amelioration and management of hyperbilirubinemia, and they emphasize that the combined dosing of retinoic acid and SnPP attenuates the suppression of the activity of HMOX, thereby decreasing plasma bilirubin levels. The features of action of retinoic acid and SnPP together in vivo, i.e., a substantial suppression of the formation of a potentially neurotoxic metabolite, bilirubin, and the enhancement of disposal of the untransformed substrate (heme) of the enzyme that is inhibited, define some of the prerequisites of a therapeutically useful formulation.