The studies conducted by this group are principally directed towards an understanding of the laboratory-mechanism for the enzymes of heme synthesis and degradation and of the influence of nutrition and endogenous and exogenous chemicals on the formation and function of Cytochrome-P450.

At clinical level, it culminated in the development of tin mesoporphyrin (SnMP), a potent inhibitor of heme oxygenase, for use in control of hyperbilirubenemia in newborns. SnMP by inhibiting bilirubin production shortly after birth eliminates the uncertainties regarding the blood level at which bilirubin may produce CNS toxicity in a given infant and the concern about treatment threshold which presently complicate the management of the new born jaundice. SnMP may provide a treatment modality for jaundiced babies born in economic and social settings where no other therapy is available for this disability and occasionally lethal medical problem.

We have also extended the work on SnPP and SnMP to determine the extent to which the alterations in the side chain substituents of the protoporphyrin macrocyclic might effect the ability of the parent compound to inhibit the heme catabolism and to suppress hyperbilirubinemia in experimental animals. The reduction of C2 and C4 vinyl to ethyl groups in CoPP to form CoMP results in a marked potentiation of the ability of metal porphyrins to induce heme oxidation in vivo and to increase serum levels in postnatal animals. Lowest effective dose of CoMP was found to increase serum bilirubin levels in animal models of physiological jaundice.

We have followed the work carried out by Prof. Attalah Kappas and Prof. George S. Drummond and explored biological essence and metal disposition of tin protoporphyrin, a potent inhibitor of heme oxygenase, which can suppress hyperbilirubinemia in various forms of experimentally induced and naturally occurring jaundice in animals. These studies raises possibility that SnPP may be used as a prenatal therapy for suppressing postnatal jaundice in Human newborns. Inhibition of brain heme oxygenase may be particularly valuable action of the compound in view of the fact that 40-50% premature babies suffer from intraventricular Hemorrhages and thus would form bilirubin in situ in CNS, if heme oxygenase was not inhibited.

These studies were also extended to study the role of Gossypol, Vitamin A & E, Progesterone, Benzene, Lead and other toxic environmental pollutants, so as to study their impact on Chemistry and Biology of Heme.

Gossypol produces both toxic and antifertility effects in mammals, prevents liberation of oxygen from deoxyhemoglobin and has a hemolytic effect on erythrocytes, as a result an extreme burden is placed upon the respiratory and circulatory organs owing to the reduced oxygen carrying capacity of blood. Gossypol stimulates the hepatic, splenic and renal ALA-S activity whereas ZnPP antagonises the gossypol mediated induction of hepatic and renal heme oxygenase activity. CoMP leads to inhibit HMOX activity and induces lipid peroxidation in spleen.

Excess Vitamin A facilitates to engulf old red blood cells, causes them to lyse, and release bilirubin. Our studies indicate the dietary constituent, Vitamin A can exert a significant regulatory effect on heme anabolic and catabolic pathways. SnPP administration to neonatal rats prevents the development of hyperbilirubinemia. We have further observed that a further attenuation in HMOX inhibition can be achieved by concurrent administration of retinoic acid and SnPP. Thus, we prognosticate that these dietary constituents can act as a competitive substrate for heme in the HMOX reaction, although it does not undergo oxidative degradation by the enzyme. Our studies highlight that the combined dose attenuates the repressing action, thus emphasizing the importance of combined rather than single exposures in defining the realms of toxicology.