J Appl Biomed 19:48-56, 2021 | DOI: 10.32725/jab.2021.006

Atorvastatin prevents the development of diabetic neuropathic nociception by possible involvement of nitrergic system

Reyhaneh Akbarian1,2, Mohsen Chamanara3, Amir Rashidian1,2, Alireza Abdollahi4, Shahram Ejtemaei Mehr1,2, Ahmad Reza Dehpour1,2,*
1 Tehran University of Medical Sciences, Experimental Medicine Research Center, Tehran, Iran
2 Tehran University of Medical Sciences, School of Medicine, Department of Pharmacology, Tehran, Iran
3 Aja University of Medical Sciences, Faculty of Medicine, Department of Pharmacology, Tehran, Iran
4 Tehran University of Medical Sciences, Imam Hospital complex, Department of Pathology, Tehran, Iran

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, co-administration 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.

Keywords: Atorvastatin; Diabetic neuropathy; Hyperalgesia; Nitric oxide; Rat
Grants and funding:

This study was part of PhD thesis and was funded and supported by a grant from Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences (TUMS), grant no. 94-03-30-29187; and Iran National Science Foundation (INSF) grant no. 96002757.

Conflicts of interest:

The authors have no conflict of interests to declare.

Received: May 9, 2020; Revised: January 18, 2021; Accepted: January 28, 2021; Prepublished online: February 9, 2021; Published: March 3, 2021  Show citation

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Akbarian R, Chamanara M, Rashidian A, Abdollahi A, Ejtemaei Mehr S, Dehpour AR. Atorvastatin prevents the development of diabetic neuropathic nociception by possible involvement of nitrergic system. J Appl Biomed. 2021;19(1):48-56. doi: 10.32725/jab.2021.006. PubMed PMID: 34907715.
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