Heme-mimetic potential of iron conjugated pheophytin-I in attenuating oxidative stress-induced cellular and vascular toxicity

Purpose of the Study: Heme is the cardinal porphyrin in systemic physiology, apart from hemoglobin it forms structural skeleton of physiological antioxidants such as catalase and peroxidases. Aim: The current study presents evidence that iron chelated pheophytin (Fe-Ph-I) created in resemblance to heme can exert significant heme-mimetic efficacy in mitigating oxidative stress-induced cellular and vascular damage. Materials and Methods: Fe-Ph-I was synthesized by incorporating ferrous ion into the porphyrin core of Ph-I moiety. The candidate drugs (Ph-I and Fe-Ph-I) were characterized by spectroscopic analysis and heme-mimetic attribute of Fe-Ph-I was established by comparing the efficacy of Fe-Ph-I with reference to its unmetallated parent Ph-I as well as un-chelated ferrous ions in a host of in vitro, ex vivo, and in vivo bioassays paradigms. Results: The study confirmed that Fe-Ph-I, Ph-I, and free ferrous ions all exerts significant in vitro anti-radical efficacy, however, while un-chelated ferrous ions intensifies, Ph-I and Fe-Ph-I mitigate ex vivo oxidative stress with Fe-Ph-I exhibiting superior potency. Also from in vivo assessment of oxidative stress-induced hemolytic anemia, it was observed that Fe-Ph-I is significantly superior than Ph-I in alleviating intravascular hemolysis, thereby endorsing that not ferrous ions alone but ferrous ion chelated with porphyrin yielding a heme-mimetic structure is responsible for superior potency of Fe-Ph-I over Ph-I. Conclusion: In conclusion, Fe-Ph-I is cost-effective and therapeutically safe biological macromolecule of clinical potency against pathologies either mediated by or themselves precipitate oxidative stress-induced cellular or vascular damage.