THE POTENTIAL RENO-PROTECTIVE EFFECT OF ALPHA-LIPOIC ACID, MELATONIN, AND THEIR COMBINATION AGAINST PARACETAMOL-INDUCED NEPHROTOXICITY IN MALE RATS.

Almosawi, Huda Ayad; Ayob Jaccob, Ausama; Al-Mozie'l, Muhsin Sagheer Ghalib

doi:10.21608/bfsa.2025.393169.2592

	THE POTENTIAL RENO-PROTECTIVE EFFECT OF ALPHA-LIPOIC ACID, MELATONIN, AND THEIR COMBINATION AGAINST PARACETAMOL-INDUCED NEPHROTOXICITY IN MALE RATS.
Bulletin of Pharmaceutical Sciences Assiut University
Articles in Press, Accepted Manuscript, Available Online from 27 July 2025
Document Type: Original Article
DOI: 10.21608/bfsa.2025.393169.2592
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Authors
Huda Ayad Almosawi ¹; Ausama Ayob Jaccob ²; Muhsin Sagheer Ghalib Al-Mozie'l ²
¹Department of pharmacology and toxicology, College of Pharmacy, University of Basrah, Basrah, Iraq
²Department of pharmacology and toxicology, College of pharmacy, University of Basrah, Basrah, Iraq
Abstract
Objective: This study aimed to investigate the potential protective effects of alpha-lipoic acid (ALA), melatonin, and their combination on paracetamol-induced renal injury in male rats. Methods: 42 rats were allocated into 6 groups: normal control (0. 75% carboxymethyl cellulose), negative control (paracetamol 3 g/kg), positive control (n-acetylcysteine 100 mg/kg), alpha-lipoic acid (100 mg/kg), melatonin (10 mg/kg), and a combination of a combination of alpha-lipoic acid (100 mg/kg) and melatonin (10 mg/kg). Treatments were administered for 14 days, followed by a single oral dose of paracetamol (3 g/kg) to induce nephrotoxicity. Serum biomarkers (urea, creatinine, total protein, glutathione) and kidney histopathology were evaluated. Results: Administration of paracetamol increased serum urea and creatinine levels and decreased glutathione levels. Treatment with alpha-lipoic acid, melatonin, and their combination ameliorated nephrotoxic markers, including improvements in glutathione and reductions in urea and creatinine, including elevation in glutathione and reductions in urea and creatinine. The combination group showed the most preserved kidney histology. Conclusion: alpha-lipoic acid and melatonin demonstrated distinct but complementary nephroprotective mechanisms against paracetamol-induced renal injury. ALA improved glutathione levels and oxidative balance, while melatonin offered greater structural and functional protection, likely via mitochondrial stabilization. These findings support their potential as adjunct therapies in managing drug-induced kidney damage.
Keywords
paracetamol; nephrotoxicity; alpha-lipoic acid; melatonin; N-acetylcysteine


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