Title:Melatonin Alleviates High Glucose-induced Oxidative Stress and
Mitochondrial Dysfunction in Chondrocytes
Volume: 19
Issue: 6
Author(s): Saeed Mehrzadi, Shokoufeh Hassani and Azam Hosseinzadeh*
Affiliation:
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
Keywords:
Melatonin, mitochondria, oxidative stress, chondrocyte, osteoarthritis, diabetes.
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.
