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 | ||||
Suez Canal University Medical Journal | ||||
Article 3, Volume 26, Issue 1, January 2023, Page 17-39 PDF (2.55 MB) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/scumj.2023.283960 | ||||
View on SCiNiTO | ||||
Authors | ||||
Marwa M. Awad 1; Rania N. Abd-Ellatif2; Sarah Ibrahim3; Maaly A. Abd Elmaaboud4; Rehab A.A. El-Shaer1 | ||||
1Physiology Department, Faculty of Medicine, Tanta University, Egypt. | ||||
2Biochemistry Department, Faculty of Medicine, Tanta University, Egypt. | ||||
3Anatomy Department, Faculty of Medicine, Tanta University, Egypt. | ||||
4Pharmacology Department, Faculty of Medicine, Tanta University, Egypt | ||||
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. | ||||
Keywords | ||||
Omega-3; cisplatin; heme oxygenase-1; hepatic toxicity and renal toxicity | ||||
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