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Melatonin alleviates arsenic-induced liver injury by regulating protein RKIP and enhancing antioxidant defencse
Soheil Rezvankhah1, Felor Zargari2, Rasoul Sharifi3
1Department of Biology, Higher Education Institute of Rab-Rashid, Tabriz, Iran.
Abstract:
Arsenic (As) is a highly toxic metal and one of the main factors in cancer development through oxidative stress and production of reactive oxygen species. Prior research has demonstrated melatonin's potential as a free radical scavenger. Raf kinase inhibitory protein (RKIP) is an important regulator of intracellular signaling pathways that has been linked to various types of cancer. The aim of this research was to explore the influence of melatonin's antioxidant properties on the expression of the protein RKIP and the antioxidant status of liver tissue in rats that were exposed to arsenic. Thirty two male Wistar rats were divided into four groups of eight, including control, melatonin-treated (20 mg/Kg of melatonin), sodium arsenite-treated (5.5 mg/Kg of sodium arsenite), and melatonin + sodium arsenite-treated groups (combination) for 4 weeks. The expression level of protein RKIP was measured by Western blot, and malondialdehyde (MDA) content of the liver as well as the activities of antioxidant enzymes were measured. The data analyzed using one-way ANOVA (significance level of p < 0.05) and GraphPad Prism (9) software. Sodium arsenite treatment led to a significant decrease in RKIP protein expression and antioxidant enzyme activity, and an increase in liver MDA levels (p < 0.001). Conversely, melatonin treatment in the combination group resulted in a significant increase in RKIP protein expression and antioxidant enzyme activity and a decrease in liver MDA levels (p < 0.05). These findings suggest that melatonin can attenuate oxidative damage caused by arsenic in liver cells by enhancing RKIP protein expression and antioxidant enzyme activity.
Insights
Melatonin protects liver cells from arsenic-induced oxidative damage by boosting Raf kinase inhibitory protein (RKIP) expression and antioxidant enzyme activity. This study highlights melatonin
Area of Science:
- Toxicology
- Biochemistry
- Molecular Biology
Background:
- Arsenic (As) is a toxic metal contributing to cancer via oxidative stress.
- Melatonin is a known free radical scavenger.
- Raf kinase inhibitory protein (RKIP) regulates signaling pathways implicated in cancer.
Purpose of the Study:
- To investigate melatonin's effect on RKIP protein expression.
- To assess melatonin's impact on antioxidant status in arsenic-exposed rat liver tissue.
Main Methods:
- Thirty-two male Wistar rats were divided into control, melatonin, sodium arsenite, and combination groups for 4 weeks.
- Western blot was used to measure RKIP protein expression.
- Liver malondialdehyde (MDA) content and antioxidant enzyme activities were quantified.
Main Results:
- Sodium arsenite significantly decreased RKIP expression and antioxidant activity while increasing MDA levels (p < 0.001).
- Melatonin administration in the combination group significantly increased RKIP expression and antioxidant activity, and decreased MDA levels (p < 0.05).
Conclusions:
- Melatonin mitigates arsenic-induced oxidative damage in liver cells.
- Enhanced RKIP protein expression and antioxidant enzyme activity are key mechanisms of melatonin's protective effect against arsenic toxicity.
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