Protective Assessment of Progesterone and Its Receptor on Experimental Diabetic Neuropathy: Antioxidant and Anti-Inflammatory Effects Publisher Pubmed



Mokhtari S¹ ; Sistani Karampour N² ; Shams MH³ ; Dehpour AR^{4, 5} ; Hasanvand A⁶ Show Affiliations
Source: Fundamental and Clinical Pharmacology Published:2023

Abstract

Diabetes induces a disorder in mitochondrial activity, which causes damage to the nuclear and mitochondrial DNA and ultimately increases the release of inflammatory cytokines and damages the sciatic nerve and dorsal root ganglion and induces neuropathy. It has been shown that progesterone has anti-inflammatory and antioxidative effects and prevents nerve cell damage. Therefore, the aim of this experiment was to investigate the effect of progesterone receptor neuroprotection on diabetic neuropathy. Forty male Sprague–Dawley rats were divided into four groups, including control group, diabetic control group, diabetic control group + progesterone (30 mg/kg), and diabetic control group + combination of progesterone (30 mg/kg) and RU486 (10 mg/kg). After the induction of diabetes, blood glucose level, body weight, behavioral tests, electrophysiological tests, oxidative and inflammatory factors, and histological parameters were measured. Progesterone treatment significantly reduced the level of sensitivity to hot plate without significant effect on glucose level, and significant changes were also observed in the results of tail flick test. In addition, the results showed that the administration of progesterone can improve MNCV and significantly reduce the serum levels of oxidative stress and inflammatory factors, as well as inflammation and edema around the sciatic nerve. However, RU486 inverted the beneficial effects of progesterone. Progesterone can be considered as a protective agent in reducing DN because of its ability to reduce inflammation and nerve damage. In addition, RU486, a progesterone receptor blocker, inhibits the beneficial effects of progesterone on the DN; thus, progesterone receptors play an important role in the neuroprotective effect of progesterone. © 2022 Societe Francaise de Pharmacologie et de Therapeutique. Published by John Wiley & Sons Ltd.