Abstract
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). Schwann cell (SC) apoptosis contributes to the occurrence and development of DPN. Effective drugs to prevent SC apoptosis are required to relieve and reverse peripheral nerve injury caused by DM. Oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione], an agonist of nuclear factor erythroid derived-2-related factor 2 (Nrf2), exerts strong effect against oxidative stress in animal models or clinical patients in certain diseases, including heart failure, acute kidney injury, and liver injury. The aim of the present study was to determine the effectiveness of oltipraz in preventing SC apoptosis induced by high glucose levels. RSC96 cells pretreated with oltipraz were cultured in high-glucose medium (50 mM glucose) for 24 h, and cells cultured in medium containing 5 mM glucose were used as the control. Flow cytometry was used to evaluate the degree of apoptosis. A Cell Counting Kit-8 assay was used to assess cell viability. The mitochondrial membrane potential was assessed using JC-1 staining, and reactive oxygen species (ROS) generation was measured using 20,70-dichlorodihydrofluorescein diacetate staining. In addition, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) levels were also evaluated using the corresponding kits. Flow cytometry was subsequently used to detect apoptosis, and western blotting was used to measure the expression levels of nuclear factor erythroid derived-2-related factor 2 and NADPH quinone oxidoreductase 1. The results showed that high glucose concentration increased oxidative stress and apoptosis in RSC96 cells. Oltipraz improved cell viability and reduced apoptosis of RSC96 cells in the high glucose environment. Additionally, oltipraz exhibited a significant antioxidative effect, as shown by the decrease in MDA levels, increased SOD levels, and reduced ROS generation in RSC96 cells. The results of the present study suggest that oltipraz exhibits potential as an effective drug for treatment with DPN.
Highlights
Diabetes mellitus (DM) is a systemic metabolic disease characterized by high blood glucose levels
Previous studies have demonstrated that apoptosis of Schwann cell (SC) induced by high glucose contributes to the development of Diabetic peripheral neuropathy (DPN) [12,13,14,15]
Effective drugs to prevent apoptosis of SCs are important for relieving and reversing peripheral nerve injury caused by DM
Summary
Diabetes mellitus (DM) is a systemic metabolic disease characterized by high blood glucose levels. DM is the most common cause of neuropathy worldwide, and up to 50% of all patients with DM may develop neuropathy [1,2,3]. Diabetic peripheral neuropathy (DPN) is a common complication of DM; ~50% of the patients with DPN are asymptomatic, whereas others may suffer from complicated symptoms such as pain, foot ulcers, and paresthesia [4, 5]. Schwann cells (SCs) are the most common type of glia in peripheral nerves. SC apoptosis induced by a high glucose environment is thought to be one of the primary causes of DPN. A previous study showed that inhibiting SC apoptosis could alleviate myelin sheath injury and delay peripheral nerve degeneration in DPN [15,16,17]
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