Atorvastatin Prevents the Development of Diabetic Neuropathic Nociception by Possible Involvement of Nitrergic System Publisher Pubmed



Akbarian R^{1, 2} ; Chamanara M³ ; Rashidian A^{1, 2} ; Abdollahi A⁴ ; Mehr SE^{1, 2} ; Dehpour AR^{1, 2} Show Affiliations
Source: Journal of Applied Biomedicine Published:2021

Abstract

Aims: Diabetic neuropathy has been identified as a common complication caused by diabetes. However, its pathophysiological mechanisms are not fully understood yet. Statins, also known as HMG-CoA reductase inhibitors, alleviate the production of cholesterol. Despite this cholesterol-reducing effect of statins, several reports have demonstrated their beneficial properties in neuropathic pain. In this study, we used streptozotocin (STZ)-induced diabetic model to investigate the possible role of nitric oxide (NO) in the antineuropathic-like effect of atorvastatin. Methods: Diabetes was induced by a single injection of STZ. Male rats orally received different doses of atorvastatin for 21 days. To access the neuropathy process, the thermal threshold of rats was assessed using hot plate and tail-flick tests. Moreover, sciatic motor nerve conduction velocity (MNCV) studies were performed. To assess the role of nitric oxide, N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), and 7-nitroindazole (7NI) were intraperitoneally administered along with some specific doses of atorvastatin. Key findings: Atorvastatin significantly reduced the hyperalgesia in diabetic rats. L-NAME pretreatment with atorvastatin showed the antihyperalgesic effect, suggesting the possible involvement of the NO pathway in atorvastatin protective action. Furthermore, coadministration of atorvastatin with AG and 7NI resulted in a significant increase in pain threshold in diabetic rats. Significance: Our results reveal that the atorvastatin protective effect on diabetic neuropathy is mediated at least in a part via the nitric oxide system. © 2021 The Authors. Published by University of South Bohemia in Ceske Budejovice, Faculty of Health and Social Sciences.