Melatonin Rescues Renal Mitochondria From Multiple Stressors–Induced Oxidative Stress

• Published in: Basic & clinical pharmacology & toxicology Vol. 136; no. 5; pp. e70031 - n/a
• Main Authors: Alshahrani, Saeed, Sultan, Muhammad H., Rashid, Hina, Alam, Firoz, Khan, Andleeb, Akhter, Mohammad Suhail, Qamri, Derayat, Beigh, Saba, Riyaz, Farhana
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.05.2025
• Subjects: Acetaminophen; Acetaminophen - toxicity; Analgesics; Animals; Antioxidants; Antioxidants - pharmacology; Benzhydryl Compounds - toxicity; Biomarkers - blood; Bisphenol A; Bisphenol A Compounds; Creatinine; Epinephrine; Hydrogen peroxide; Inflammation; Interleukin 6; kidney; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Male; Melatonin; Melatonin - pharmacology; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Phenols - toxicity; Proteins; Rats; Rats, Wistar; Renal function; Superoxide dismutase; Toxins; Tumor necrosis factor-α; Uric acid; Xenobiotics; kidney; acetaminophen; bisphenol A; inflammation; mitochondria; oxidative stress
• ISSN: 1742-7835; 1742-7843; 1742-7843
• DOI: 10.1111/bcpt.70031

ABSTRACT The renal system is a significant organ system vulnerable to stress due to its physiological function of toxin elimination. Exposure to a wide array of xenobiotics in humans causes deleterious effects in the kidneys. In the present study, we observed the toxic effect of a coexposure of bisphenol A and acetaminophen on the renal function and renal mitochondria of Wistar rats and its amelioration by melatonin. The animals were grouped and treated for 4 weeks as follows: (I) control; (II) melatonin; (III) bisphenol A; (IV) acetaminophen; (V) bisphenol A and acetaminophen; and (VI) bisphenol A, acetaminophen and melatonin. Coadministration of bisphenol A and acetaminophen exposure significantly impaired renal function, elevating creatinine (2.28 mg/dL), BUN (65.42 mg/dL) and uric acid (6.11 mg/dL), while increasing oxidative stress and inflammatory markers (CAT: 3.85‐μmol H2O2/min/mg protein, GPx: 189.57‐nmol NADPH/min/mg protein, GR: 96.62‐nmol NADPH/min/mg protein, MnSOD: 107.24‐nmol (−) epinephrine/min/mg protein, IL‐6: 1750 pg/mL, TNFα: 1677 pg/mL). Melatonin coadministration improved renal markers (creatinine: 1.60 mg/dL, BUN: 45.59 mg/dL, uric acid: 4.61 mg/dL) and partially restored antioxidant defences and inflammatory markers (CAT: 5.74‐μmol H2O2/min/mg protein, GPx: 422.74‐nmol NADPH/min/mg protein, GR: 136.91‐nmol NADPH/min/mg protein, MnSOD: nmol (−) epinephrine prevented from oxidation/min/mg protein, IL‐6: 1677 pg/mL, TNFα: 900 pg/mL). These findings suggest that melatonin mitigates bisphenol A and acetaminophen‐induced renal damage by enhancing antioxidant defences and reducing inflammation.