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Document Type

Original Study

Subject Areas

Pharmacology and Toxicology

Keywords

Apoptosis, Coenzyme Q10, Cyclosporine A, Fibrosis, Indole-3-carbinol, nephrotoxicity.

Abstract

Background: Cyclosporine A (CsA) is a potent immunosuppressive drug, with nephrotoxicity being its most frequent adverse effect, primarily due to the involvement of free radicals in inflammatory and fibrotic pathways. Both coenzyme Q10 (CoQ10), a fat-soluble vitamin-like molecule, and indole-3-carbinol (I3C), a natural compound, possess anti-inflammatory and antioxidant properties. Aim: This study aimed to investigate the potential protective effects of CoQ10 and/or I3C against CsA-induced nephrotoxicity in rats. Methods: Male albino rats were randomly assigned to five groups, with six rats in each group. Group (1) served as the normal control group and received corn oil orally by gavage for 28 days. Groups (2-5) received CsA (25 mg/kg/day, p.o) starting from the second week of the experiment for 21 days. Groups (3-5) were treated with CoQ10 (10 mg/kg/day, p.o), I3C (20 mg/kg/day, p.o), or a combination of CoQ10 and I3C, respectively, for 28 days. Results: CsA administration resulted in an elevation of kidney parameters, alterations in oxidative stress markers (GSH, MDA, NO), and increased levels of tissue inflammatory, apoptotic, and fibrotic markers (TNF-α, caspase-3, and endothelin-1, respectively). Immunohistochemical analysis of the kidneys in the CsA group showed increased expression of NF-κB, Bcl2, Bax, and TGF-β. Histopathological examination using Masson’s trichrome staining revealed moderate positive staining for perivascular and periglomerular collagen fiber deposition. Treatment with CoQ10 and/or I3C ameliorated oxidative stress, inflammation, apoptosis, and fibrosis in CsA-treated rats. Conclusion: Our study demonstrated that CoQ10 and/or I3C mitigate renal dysfunction and abnormalities associated with CsA administration, indicating their therapeutic potential against CsA-induced nephrotoxicity. Their renoprotective effects are likely mediated through anti-apoptotic, anti-fibrotic, anti-inflammatory, and antioxidant mechanisms.

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