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Evaluating the Protective Effect of Melatonin on Atorvastatin-induced Mitochondrial Toxicity in Pancreatic Beta Cells
Saeed Mehrzadi1, Asieh Hosseini1, Azam Hosseinzadeh1
1Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
Background:
Atorvastatin and other statins belong to a category of cholesterollowering drugs, which may cause some damage to pancreatic cells despite their effectiveness.
Aims:
The present study investigated the effects of melatonin against atorvastatin-induced toxicity on islets of Langerhans and CRI-D2 cells.
Methods:
The MTT assay was used to determine cell viability. The effect of various concentrations of melatonin (0,10, 50, 100, 250, 500 and 1000 μM) on CRI-D2 cell viability was evaluated for 24 hours to determine the non-cytotoxic concentrations of melatonin. Additionally, cells were treated with different concentrations of atorvastatin (10, 100, and 150 ng/mL) for 24 hours to determine a concentration that could induce the maximum cell death. After selecting the appropriate concentrations for melatonin, cells were treated with atorvastatin (10, 100, and 150 ng/ml) and melatonin (10 and 100 μM) simultaneously for a period of 24 hours. Malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase, catalase, and glutathione peroxidase activity were assessed as indicators of oxidative stress. To assess mitochondrial function, the ratio of adenosine diphosphate (ADP) to adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) were measured.
Results:
Atorvastatin markedly raised ROS and MDA levels. This result was associated with a decrease in MMP, an increase in the ADP/ATP ratio, and a change in the activity of antioxidant enzymes. Atorvastatin (150 ng/mL)-induced mitochondrial damage was alleviated by concurrent melatonin and atorvastatin therapy.
Conclusion:
These results suggest that melatonin has a protective effect against atorvastatininduced toxicity in the mitochondria of pancreatic cells.
Insights
Melatonin protects pancreatic cells from atorvastatin toxicity by reducing oxidative stress and improving mitochondrial function. This study highlights melatonin
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Statins, like atorvastatin, are effective cholesterol-lowering drugs but can induce pancreatic cell damage.
- Understanding the mechanisms of statin-induced pancreatic toxicity is crucial for patient safety.
Purpose of the Study:
- To investigate the protective effects of melatonin against atorvastatin-induced toxicity in pancreatic cells (islets of Langerhans and CRI-D2 cells).
- To evaluate melatonin's impact on oxidative stress and mitochondrial function markers.
Main Methods:
- Cell viability was assessed using the MTT assay.
- Cells were exposed to varying concentrations of atorvastatin and melatonin.
- Oxidative stress markers (ROS, MDA) and mitochondrial function (ADP/ATP ratio, MMP) were measured.
Main Results:
- Atorvastatin significantly increased oxidative stress (ROS, MDA) and impaired mitochondrial function (decreased MMP, increased ADP/ATP ratio).
- Concurrent treatment with melatonin alleviated atorvastatin-induced mitochondrial damage.
- Melatonin demonstrated a protective effect against atorvastatin's detrimental impact on pancreatic cells.
Conclusions:
- Melatonin exhibits a protective role against atorvastatin-induced pancreatic cell toxicity.
- The findings suggest melatonin's potential therapeutic application in mitigating statin-related side effects.
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