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Melatonin protected against kidney impairment induced by 5-fluorouracil in mice
Mona E Elbanan1, Maggie E Amer1, Mohamed A El-Missiry1
1Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt.
Abstract:
The utility of 5-fluorouracil (5-FU) as a successful chemotherapeutic drug for several cancers is limited by the induction of kidney injury and dysfunction due to redox imbalance, inflammation, and apoptosis. Meanwhile, melatonin (MLT) is a potent antioxidant and anti-inflammatory natural compound with a wide safety range. The current study aimed to investigate MLT's protective effect against 5-FU-induced kidney impairment. Male mice were given multiple doses of 5-FU at 25 and 100 mg/kg, as well as MLT at 20 mg/kg. MLT treatment alleviated the toxic effect of 5-FU by normalizing blood urea and creatinine levels and preserving the histological structure, indicating MLT's nephroprotective ability. This is accompanied by body weight maintenance, an increase in survival percentage, and preserved hematological parameters in comparison to the 5-FU-treated mice. MLT's renoprotective effect was explained by improvements in C-reactive protein, IL-6, and caspase-3 in kidney tissue, indicating MLT's anti-inflammatory and antiapoptotic ability. Furthermore, MLT inhibited 5-FU-induced lipid peroxidation by maintaining the activity of superoxide dismutase and catalase, as well as glutathione levels in kidney tissue from mice treated with both doses of 5-FU. The current findings show that MLT has a novel protective effect against 5-FU-induced renal injury and renal impairment.
Insights
Melatonin (MLT) protects against 5-fluorouracil (5-FU) induced kidney damage by reducing inflammation and oxidative stress. This study shows MLT’s potential as a protective agent against chemotherapy-related renal impairment.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- 5-fluorouracil (5-FU) is a chemotherapy drug with limited utility due to kidney injury caused by redox imbalance, inflammation, and apoptosis.
- Melatonin (MLT) is a natural compound with antioxidant and anti-inflammatory properties and a broad safety profile.
Purpose of the Study:
- To investigate the protective effects of melatonin against 5-fluorouracil-induced kidney impairment in a mouse model.
Main Methods:
- Male mice were administered 5-FU (25 and 100 mg/kg) with or without MLT (20 mg/kg).
- Evaluated kidney function markers (blood urea, creatinine), histological structure, body weight, survival rate, hematological parameters, and kidney tissue markers (C-reactive protein, IL-6, caspase-3, lipid peroxidation, superoxide dismutase, catalase, glutathione).
Main Results:
- MLT treatment normalized blood urea and creatinine levels, preserved kidney histology, and improved body weight and survival rates in 5-FU treated mice.
- MLT reduced inflammatory markers (C-reactive protein, IL-6) and apoptotic markers (caspase-3) in kidney tissue.
- MLT inhibited lipid peroxidation and maintained antioxidant enzyme activity (superoxide dismutase, catalase) and glutathione levels, indicating reduced oxidative stress.
Conclusions:
- Melatonin demonstrates significant nephroprotective effects against 5-FU-induced renal injury.
- MLT mitigates 5-FU toxicity by exerting anti-inflammatory, antiapoptotic, and antioxidant actions.
- Melatonin shows promise as a therapeutic agent to prevent or reduce chemotherapy-induced kidney damage.
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