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Melatonin Rescues Renal Mitochondria From Multiple Stressors-Induced Oxidative Stress
Saeed Alshahrani1, Muhammad H Sultan2, Hina Rashid1
1Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jizan, Saudi Arabia.
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.
Insights
This study shows that combined exposure to bisphenol A and acetaminophen harms kidney function in rats. Melatonin treatment protected against this damage by reducing oxidative stress and inflammation.
Area of Science:
- Toxicology
- Renal Physiology
- Mitochondrial Biology
Background:
- The kidneys are vital for toxin elimination and susceptible to damage from xenobiotics.
- Bisphenol A (BPA) and acetaminophen are common environmental and pharmaceutical agents with potential nephrotoxic effects.
- Understanding the combined impact of these agents and potential protective strategies is crucial for public health.
Purpose of the Study:
- To investigate the toxic effects of coexposure to bisphenol A and acetaminophen on renal function and mitochondria in Wistar rats.
- To evaluate the potential protective role of melatonin against BPA and acetaminophen-induced nephrotoxicity.
- To assess the impact on oxidative stress and inflammatory markers.
Main Methods:
- Wistar rats were divided into six groups and treated for four weeks.
- Groups included control, melatonin alone, BPA alone, acetaminophen alone, BPA + acetaminophen, and BPA + acetaminophen + melatonin.
- Renal function markers, oxidative stress markers (CAT, GPx, GR, MnSOD), and inflammatory markers (IL-6, TNFα) were measured.
Main Results:
- Coadministration of BPA and acetaminophen significantly elevated serum creatinine, BUN, and uric acid levels.
- Combined exposure increased oxidative stress and inflammation markers (IL-6, TNFα).
- Melatonin treatment partially restored renal function markers and antioxidant defenses, while reducing inflammation.
Conclusions:
- Combined exposure to bisphenol A and acetaminophen induces significant renal damage.
- Melatonin demonstrates a protective effect against this induced nephrotoxicity.
- Melatonin mitigates renal damage by enhancing antioxidant capacity and reducing inflammation.
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