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Alpha-lipoic acid modulates the diabetes mellitus-mediated neuropathic pain via inhibition of the TRPV1 channel, apoptosis, and oxidative stress in rats   
Yazarlar
Dr. Öğr. Üyesi Betül YAZĞAN
Kastamonu Üniversitesi
Dr. Öğr. Üyesi Yener YAZĞAN
Kastamonu Üniversitesi
Mustafa Naziroglu
Özet
Diabetes mellitus (DM) is a chronic syndrome involving neuropathic pain. Increased oxidative stress in DM is assumed to increase free reactive oxygen radicals (ROS) and causes diabetic damage. The sciatic nerve (ScN) and dorsal root ganglion (DRG) both contain high levels of the TRPV1 channel, which is triggered by capsaicin and ROSs and results in increased Ca entry into the neurons. Alpha-lipoic acid (ALA) is considered an important part of the antioxidant system. To better characterize the protective effects of ALA on the DM-induced neuronal through TRPV1 modulation, we investigated the role of ALA on DM-induced neuropathic pain, oxidative ScN, and DRG damage in diabetic rats. Forty adult Wistar albino female rats were divided into four groups as control, ALA (50 mg/kg for 14 days), streptozotocin (STZ and 45 mg/kg and single dose), and STZ + ALA. Rats were used for the pain tests. After obtaining the DRGs and ScN, they were used for plate reader, patch-clamp, and laser confocal microscope analyses. We observed the modulator role of ALA on the thresholds of mechanical withdrawal pain (von Frey test) and hot sensitivity pain (hot plate test) in the STZ + ALA group. The treatment of ALA decreased STZ-induced increase of TRPV1 current densities, intracellular free Ca concentrations (Fura-2 and Fluo - 3/AM), ROS, caspase 3, caspase 9, mitochondrial membrane potential, and apoptosis values in the ScN and DRG neurons, although its treatment induced the increase of cell viability and body weight gain. The treatment of ALA acted a neuroprotective role on the TRPV1 channel stimulation-mediated Ca influx, neuropathic pain, and neuronal damage in diabetic rats. The neuroprotective role of ALA treatment can be explained by its modulating the TRPV1 channel activity, intracellular Ca increase-induced oxidative stress, and apoptosis.
Anahtar Kelimeler
Alpha-lipoic acid | Apoptosis | Neuropathic pain | Oxidative stress | TRPV1 channel
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
Dergi ISSN 0145-479X
Dergi Grubu Q3
Makale Dili İngilizce
Basım Tarihi 06-2023
Cilt No 55
Sayı 3
Sayfalar 179 / 193
Doi Numarası 10.1007/s10863-023-09971-w