Abstract
Metabolic abnormalities including hyperglycemia, hyperlipidemia, and oxidative-nitrosative stress are involved in the progression of diabetic neuropathy. In the present study, we targeted oxidative-nitrosative stress using nebivolol, a β1-receptor antagonist with vasodilator and antioxidant property, to evaluate its neuroprotective effect in streptozotocin-induced diabetic neuropathy in rats. Diabetic neuropathy develops within 4–6 weeks after administration of streptozotocin (55 mg/kg, i.p.). Therefore, after confirmation of diabetes, subtherapeutic doses of nebivolol (1 and 2 mg/kg, p.o./day) were given to diabetic rats for 8 weeks. Nebivolol treatment significantly improved thermal hyperalgesia, grip strength, and motor coordination. Nebivolol also reduced levels of malondialdehyde, tumor necrosis factor-α, and nitrite in diabetes. Moreover, nebivolol increased the levels of superoxide dismutase and catalase in sciatic nerve homogenate of diabetic rats. Further, nebivolol exerted positive effects on lipid profile, sciatic nerve’s morphological changes and nerve conduction velocity in diabetic rats. Results of the present study suggest the neuroprotective effect of nebivolol through its antioxidant, nitric oxide-potentiating, and antihyperlipidemic activity.
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The authors are thankful to the Indian Council of Medical Research (ICMR) New Delhi, India, for providing senior research fellowship to the corresponding author.
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The corresponding author is receiving a Senior Research Fellowship (SRF) from the Indian Council of Medical Research (ICMR), New Delhi, India (fellowship no. 45/21/2013/PHA-BMS).
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Experimental procedures were performed in accordance with the guidelines of the Institutional Animal Ethics Committee of CPCSEA, India (approval no. AACP/IAEC/July-2013/01).
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Bhadri, N., Razdan, R. & Goswami, S.K. Nebivolol, a β-blocker abrogates streptozotocin-induced behavioral, biochemical, and neurophysiological deficit by attenuating oxidative-nitrosative stress: a possible target for the prevention of diabetic neuropathy. Naunyn-Schmiedeberg's Arch Pharmacol 391, 207–217 (2018). https://doi.org/10.1007/s00210-017-1450-8
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DOI: https://doi.org/10.1007/s00210-017-1450-8