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Melatonin, a pineal hormone with antioxidant property, protects against gentamicin-induced nephrotoxicity in rats
A A Shifow1, K V Kumar, M U Naidu
1Central Research Laboratory, Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India.
Abstract:
The present study investigated the effects of melatonin, an antioxidant, on gentamicin-induced nephrotoxicity in rats. Melatonin (5 mg/kg p.o.) was used 3 days before and 8 days simultaneously with gentamicin (80 mg/kg i.p.) Saline-treated animals served as controls. Determinations of urinary creatinine, N-acetyl-beta-D-glucosaminidase, glucose, protein, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde (MDA), and antioxidant enzyme levels in kidney tissue were done after 8 days of gentamicin treatment. The kidneys were also examined for morphological changes using histological techniques. Gentamicin caused nephrotoxicity as evidenced by marked elevation in blood urea and serum creatinine. Mean blood urea and serum creatinine levels were 289+/-50, and 2.5+/-0.5 mg/dl, respectively, in rats treated with gentamicin. Melatonin significantly protected the rats from gentamicin-induced nephrotoxicity; blood urea and serum creatinine levels were 23+/-2.7 and 0.88+/-0.19 mg/dl, respectively. The creatinine clearance was decreased with gentamicin treatment (0.048+/- 0.007 ml/min) as compared with controls (0.41+/-0.08 ml/h/kg). In rats treated with melatonin plus gentamicin, the creatinine clearance was similar to controls (0.41+/-0.08 ml/h/kg). The product of lipid peroxidation (MDA) was markedly increased in plasma (2.10+/-0.15 nmol) and kidney tissue (8.87+/-3.2 nmol/mg protein) with gentamicin treatment. Melatonin prevented the gentamicin-induced rise in plasma MDA (1.03+/-0.27 nmol) and kidney tissue MDA (2.57+/-0.87 nmol/mg protein). An increased excretion of urinary N-acetyl-beta-D-glucosaminidase, glucose, and protein by gentamicin was also prevented by melatonin. Kidneys from gentamicin-treated rats showed tubular epithelial loss with intense granular degeneration involving more than 50% of renal cortex, while there were findings comparable to controls in melatonin plus gentamicin treated rats. The present study indicates that melatonin significantly protects against gentamicin-induced renal toxicity in Wistar rats.
Insights
Melatonin, an antioxidant, significantly protects against gentamicin-induced nephrotoxicity in rats. It reduced elevated blood urea and serum creatinine levels, prevented lipid peroxidation, and preserved kidney structure.
Area of Science:
- Pharmacology and Toxicology
- Nephrology
- Biochemistry
Background:
- Gentamicin is a widely used antibiotic with known nephrotoxic potential.
- Nephrotoxicity induced by gentamicin can lead to significant kidney damage.
- Antioxidants are being investigated for their protective effects against drug-induced organ damage.
Purpose of the Study:
- To investigate the protective effects of melatonin against gentamicin-induced nephrotoxicity in Wistar rats.
- To evaluate the impact of melatonin on biochemical markers and histological changes associated with gentamicin toxicity.
- To assess melatonin's role as an antioxidant in mitigating kidney damage.
Main Methods:
- Rats were treated with gentamicin (80 mg/kg i.p.) and melatonin (5 mg/kg p.o.) or saline as control.
- Biochemical parameters including blood urea, serum creatinine, creatinine clearance, and malondialdehyde (MDA) were measured.
- Urinary markers (creatinine, N-acetyl-beta-D-glucosaminidase, glucose, protein) and kidney histology were assessed.
Main Results:
- Gentamicin treatment significantly increased blood urea, serum creatinine, and MDA levels, while decreasing creatinine clearance.
- Melatonin administration significantly reduced these markers, bringing them closer to control levels.
- Histological examination revealed that melatonin protected against gentamicin-induced tubular damage and degeneration.
Conclusions:
- Melatonin exhibits significant nephroprotective effects against gentamicin-induced renal toxicity in rats.
- Melatonin's antioxidant properties appear to play a key role in preventing gentamicin-induced kidney damage.
- These findings suggest melatonin as a potential therapeutic agent to mitigate gentamicin nephrotoxicity.