Role of Heme Oxygenase (HO)-1 Enzyme in the Protective and Therapeutic Effect of Omega 3 Fatty Acids on Cisplatin-induced Hepatic and Renal Toxicity in Rats

Awad, Marwa M.; Abd-Ellatif, Rania N.; Ibrahim, Sarah; Abd Elmaaboud, Maaly A.; El-Shaer, Rehab A.A.

doi:10.21608/scumj.2023.283960

Role of Heme Oxygenase (HO)-1 Enzyme in the Protective and Therapeutic Effect of Omega 3 Fatty Acids on Cisplatin-induced Hepatic and Renal Toxicity in Rats

Document Type : Original Article

Authors

¹ Physiology Department, Faculty of Medicine, Tanta University, Egypt.

² Biochemistry Department, Faculty of Medicine, Tanta University, Egypt.

³ Anatomy Department, Faculty of Medicine, Tanta University, Egypt.

⁴ Pharmacology Department, Faculty of Medicine, Tanta University, Egypt

10.21608/scumj.2023.283960

Abstract

Background: Cisplatin is frequently used as an anticancer medication. Nephrotoxicity and hepatotoxicity are triggered by its usage, causing patients to limit their long-term therapy. Aim: To investigate the underlying mechanism of omega-3 (fatty acids) effect on hepatorenal toxicity induced by cisplatin in rats and to detect whether it has a protective or therapeutic effect or both and the role of HO-1 enzyme in both effects. Materials and Methods: 40 male rats were divided into four equal groups: Control group: received i.p. saline+ corn oil orally, Cisplatin Group: received i.p. CP (12 mg/kg)+ corn oil orally, Cisplatin+ ω-3 pretreatment group: received i.p. CP following 10 days of ω-3 pretreatment in dose {(270 mg/kg) EPA, (180 mg/kg)} and Cisplatin+ ω-3 post-treatment group: received i.p. CP followed by 10 days of ω-3 post-treatment in dose as the previous group. Liver and kidney function, serum (HO-1), serum& tissue (TNF-α, IL-10), tissue (NFkB, GSH, MDA), and NrF2 gene expressions were measured. Results: Cisplatin-induced marked hepatorenal failure; detected by elevation of serum: AST, ALT, creatinine, and urea. Also, serum& tissue (TNF-α, IL-10), and tissue (NFkB, GSH, MDA) were significantly changed with no change in NrF2 gene expressions as compared to the control. On other hand, pre or post-ω-3 intake significantly corrected the changed markers. Liver and renal histopathological and immunohistochemical changes confirmed the biochemical results in all groups. Conclusion: Cisplatin treatment impairs liver and kidney function, while ω-3 supplementation could avoid this toxicity, with the protective response appearing to be more beneficial than the therapeutic effect.

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