Involvement of TRPM7 Channel on the Induction of Diabetic Neuropathic Pain in Mice: Protective Role of Selenium and Curcumin.

Bünyamin Aydın, Mustafa Nazıroğlu
Author Information
  1. Bünyamin Aydın: Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kutahya Health Sciences University, Kutahya Evliya Çelebi Training and Research Hospital, TR-64100, Kutahya, Turkey.
  2. Mustafa Nazıroğlu: Neuroscience Research Center (NOROBAM), Suleyman Demirel University, TR-32260, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr. ORCID

Abstract

Excessive levels of the mitochondrial reactive oxygen radical (mitSOX) and Ca influx were found to cause neuropathic pain in patients with diabetes mellitus (DM). Naltriben (NLT) and mitSOX activate the transient receptor (TRP) melastatin 7 (TRPM7) channel, but antioxidants and carvacrol inhibit it. Selenium (Se) and curcumin (CRC) have been thoroughly studied for their modulator effects on streptozotocin (STZ)-induced neuropathic pain, apoptosis, and oxidative stress through the blockage of TRP channels in dorsal root ganglion (DRG) neurons. It has not yet been fully understood how Se and CRC protect against STZ-induced neuropathic pain by modulating TRPM7. Here, we assessed how Se and CRC affected the Ca influx, mitSOX-mediated oxidative damage, and apoptosis in the DRGs of mice through modifying TRPM7 activity. Seven groups (control, Se, CRC, STZ, STZ + Se, STZ + CRC, and STZ + Se + CRC) were induced from the 56 male mice. We observed that the STZ-induced stimulation of TRPM7 increased mechanical neuropathic pain (von Frey), thermal neuropathic pain (hot plate), cytosolic Ca, TRPM7 current density, TRPM7 expression, lipid peroxidation, mitSOX, cytosolic ROS, apoptosis, caspase-3, caspase-8, and caspase-9 concentrations, whereas Se and CRC therapies diminished the alterations. The STZ-mediated decreases of DRG viability, brain glutathione, glutathione peroxidase, vitamin A, and vitamin E concentrations were also upregulated in the treatment groups by the therapies. These findings collectively imply that an imbalance of neuropathic pain, oxidative neurotoxicity, and apoptosis in the mice is caused by the STZ-mediated activation of TRPM7. However, the downregulation of TRPM7 activity caused by the injections of Se and CRC reduced the neurotoxicity and apoptosis.

Keywords

References

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Grants

  1. 2021-09/by BSN Health, Analyses, Innov., Consult., Org., Agricul., Industry LTD., Isparta, Turkey.

MeSH Term

Mice
Male
Animals
Selenium
Curcumin
TRPM Cation Channels
Antioxidants
Oxidative Stress
Streptozocin
Neuralgia
Diabetes Mellitus

Chemicals

Selenium
Curcumin
TRPM Cation Channels
Antioxidants
Streptozocin
Trpm7 protein, mouse

Word Cloud

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