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铁共轭脱镁叶绿素-I在减轻氧化应激诱导的细胞和血管毒性方面的拟血红素潜力

Heme-Mimetic Potential of Iron Conjugated Pheophytin-I in Attenuating Oxidative Stress-Induced Cellular and Vascular Toxicity.

作者信息

Das Debashree, Patil Shailendra, Gajbhiye Asmita

机构信息

Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh, India.

Swami Vivekanand Institute of Pharaceutical Sciences, Faculty of Pharmacy, Swami Vivekanand University, Sagar, Madhya Pradesh, India.

出版信息

J Pharm Bioallied Sci. 2022 Jul;14(Suppl 1):S115-S122. doi: 10.4103/jpbs.jpbs_654_21. Epub 2022 Jul 13.

DOI:10.4103/jpbs.jpbs_654_21
PMID:36110651
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9469245/
Abstract

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 , and bioassays paradigms.

RESULTS

The study confirmed that Fe-Ph-I, Ph-I, and free ferrous ions all exerts significant anti-radical efficacy, however, while un-chelated ferrous ions intensifies, Ph-I and Fe-Ph-I mitigate oxidative stress with Fe-Ph-I exhibiting superior potency. Also from 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.

摘要

研究目的

血红素是全身生理学中的主要卟啉，除血红蛋白外，它还构成过氧化氢酶和过氧化物酶等生理抗氧化剂的结构骨架。

研究目标

当前研究表明，模仿血红素合成的铁螯合脱镁叶绿素（Fe-Ph-I）在减轻氧化应激诱导的细胞和血管损伤方面具有显著的血红素模拟功效。

材料与方法

通过将亚铁离子掺入Ph-I部分的卟啉核心中来合成Fe-Ph-I。通过光谱分析对候选药物（Ph-I和Fe-Ph-I）进行表征，并通过在一系列细胞和生物测定范式中比较Fe-Ph-I与其未金属化的母体Ph-I以及未螯合的亚铁离子的功效，确定Fe-Ph-I的血红素模拟特性。

结果

研究证实，Fe-Ph-I、Ph-I和游离亚铁离子均具有显著的抗自由基功效，然而，未螯合的亚铁离子会加剧氧化应激，而Ph-I和Fe-Ph-I则可减轻氧化应激，其中Fe-Ph-I表现出更强的效力。此外，通过对氧化应激诱导的溶血性贫血的评估，观察到Fe-Ph-I在减轻血管内溶血方面明显优于Ph-I，从而证实，产生血红素模拟结构的卟啉螯合亚铁离子而非单独的亚铁离子，是Fe-Ph-I比Ph-I效力更强的原因。

结论

总之，Fe-Ph-I是一种具有成本效益且治疗安全的生物大分子，对由氧化应激诱导的细胞或血管损伤介导或自身引发的病症具有临床效力。

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