Abstract
Background: Hyperglycemia triggers mitochondrial dysfunction in chondrocytes, potentially contributing to cell damage and the onset of osteoarthritis.
Objective: This study is undertaken with the objective of examining the protective properties of melatonin against toxicity induced by high glucose in C28I2 human chondrocytes.
Methods: To determine non-cytotoxic concentrations of melatonin, various concentrations (10, 25, 50, 75, 100, 500, and 1000 μM) were assessed over different time periods (24, 48, and 72 hours) for their impact on C28I2 cell viability. Following this, cells underwent a pretreatment with melatonin (10 and 100 μM) for 6 hours. This was followed by subjecting the cells to a high concentration of glucose (75 mM) for 48 hours. Oxidative stress markers, including reactive oxygen species (ROS) and malondialdehyde (MDA), alongside the enzymatic activities of glutathione peroxidase, superoxide dismutase, and catalase were quantitatively assessed. To assess mitochondrial function, we evaluated the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio and measured the mitochondrial membrane potential (MMP).
Results: Elevated glucose levels significantly increased ROS and MDA levels, accompanied by reduced MMP, an elevated ADP/ATP ratio, and altered antioxidant enzyme activity. Pretreatment with melatonin effectively reversed the mitochondrial toxicity induced by high glucose (75 mM).
Conclusion: These results indicate that melatonin exhibits a protective influence against hyperglycemia- induced toxicity in chondrocyte mitochondria.
Graphical Abstract
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