Effect of mitoquinone (Mito-Q) on neuropathic endpoints in an obese and type 2 diabetic rat model. (3rd May 2020)

• Record Type: Journal Article
• Authors: Fink, Brian; Coppey, Lawrence; Davidson, Eric; Shevalye, Hanna; Obrosov, Alexander; Chheda, Pratik Rajesh; Kerns, Robert; Sivitz, William; Yorek, Mark
• Is Part Of: Free radical research. Volume 54:Number 5(2020)
• Page Start: 311
• Page End: 318
• Publication Date: 2020-05-03
• Subjects: Peripheral neuropathy -- diabetes -- obesity -- mitoquinone -- oxidative stress; Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• DOI: 10.1080/10715762.2020.1754409
• Languages: English
• ISSNs: 1071-5762

Abstract

Abstract: This study sought to determine whether the addition of mitoquinone (Mito-Q) in the diet is an effective treatment for peripheral neuropathy in animal models of diet-induced obesity (pre-diabetes) and type 2 diabetes. Unlike other anti-oxidative stress compounds investigated as a treatment for peripheral neuropathy, Mito-Q specifically targets mitochondria. Although mito-Q has been shown to reduce oxidative stress generated by mitochondria there have been no studies performed of the effect of Mito-Q on peripheral neuropathy induced by diet-induced obesity or type 2 diabetes. Diet-induced obese (12 weeks after high fat diet) or type 2 diabetic rats (12 weeks of high fat diet and 4 weeks after the onset of hyperglycemia) were treated via the diet with Mito-Q (0.93 g/kg diet) for 12 weeks. Afterwards, glucose utilization, vascular reactivity of epineurial arterioles to acetylcholine and peripheral neuropathy related endpoints were examined. The addition of Mito-Q to the diets of obese and diabetic rats improved motor and/or sensory nerve conduction velocity, cornea and intraepidermal nerve fibre density, cornea sensitivity and thermal nociception. Surprisingly, treating obese and diabetic rats with Mito-Q did not improve glucose utilization or vascular reactivity by epineurial arterioles to acetylcholine. These studies imply that mitochondrial dysfunction contributes to peripheral neuropathy in animal models of pre-diabetes and late-stage type 2 diabetes. However, improvement in peripheral neuropathy following treatment with Mito-Q was not associated with improvement in glucose utilization or vascular reactivity of epineurial arterioles to acetylcholine.