Melatonin protects MG63 osteoblast-like cells from hydrogen peroxide-induced cytotoxicity by maintaining mitochondrial function

Abstract

Osteoporosis is a bone disease that has been connected with reactive oxygen species (ROS)-induced cytotoxicity. Mitochondrial dysfunction may be involved in the mechanism underlying ROS-induced cytotoxicity. It has been demonstrated that melatonin may exert cytoprotective effects by improving mitochondrial energetics and functions in several models of oxidative damage. In the present study, the MG63 osteoblast-like cell line was exposed to different concentrations of hydrogen peroxide (H2O2; 0, 100, 200, 400 or 800 µM) for 8 h, and 200 or 400 µM H2O2 for various periods of time (0.5, 4, 8 or 12 h). Results showed that H2O2 significantly reduced cell viability, increased the release of lactate dehydrogenase, increased the levels of ROS and malondialdehyde, reduced the concentration of adenosine-5'-triphosphate, disrupted the mitochondrial membrane potential (ΔΨm) and decreased the mitochondrial DNA copy number in MG63 cells. However, pretreatment with melatonin effectively decreased all of these H2O2-induced changes in cytotoxicity and mitochondrial dysfunction in MG63 cells. The protective effects of melatonin may be attributed to its ability to maintain mitochondrial function in H2O2-treated cells. This study suggests that melatonin is a potential pharmacological agent for preventing ROS-induced bone loss in diseases such as osteoporosis.

Melatonin: Another avenue for treating osteoporosis?

“…The results showed that H 2 O 2 significantly reduces cell viability and the concentration of adenosine‐5′‐triphosphate and increases the levels of lactate dehydrogenase (LDH), ROS, and malondialdehyde, which further reduces the mitochondrial membrane potential and mitochondrial DNA copy number in MG63 cells. However, pretreatment with melatonin effectively reverses all of these H 2 O 2 ‐induced changes in cytotoxicity and mitochondrial dysfunction in MG63 cells, suggesting the protective effects of melatonin in maintaining oxidative homeostasis and mitochondrial function in H 2 O 2 ‐treated cells . Yildirimturk et al found that melatonin administration reduces oxidative stress‐related biomarkers and shows beneficial effects on short‐term bone formation and healing in streptozotocin (STZ)‐induced diabetic rats.…”

Sirt3–MnSOD axis represses nicotine-induced mitochondrial oxidative stress and mtDNA damage in osteoblasts

“…The inhibition of mitochondrial ROS is considered to be better than global ROS inhibition for therapy of diverse disorders [10]. Mitochondria oxidative stress and dysfunction essentially contribute to osteoporosis through regulating processes including mitophagy, apoptosis, and mitochondrial DNA (mtDNA) damage [11][12][13]. So, the improvement of mitochondrial function could protect osteoblast cells from cytotoxicity and dysfunction [12,14].…”

Attenuation of Oxidative Stress-Induced Osteoblast Apoptosis by Curcumin is Associated with Preservation of Mitochondrial Functions and Increased Akt-GSK3β Signaling

“…Mitochondrial dysfunction essentially influences osteoblasts through the regulation of mitophagy, apoptosis, and mitochondrial DNA damage [8][9][10]. Improving mitochondrial functions through the application of antioxidants can prevent cytotoxicity and dysfunction in osteoblasts [9,11]. Curcumin is a naturally occurring yellow molecule in turmeric, which demonstrates potent antioxidant and anti-inflammatory properties [12,13].…”