Behavioral and biochemical evaluation of the neuroprotective role of naringin in streptozotocin-induced diabetic peripheral neuropathy in rats

Abstract

Aim: Diabetic neuropathy is the most prevalent diabetic complication, impacting up to 60% of people with diabetes. It is characterized by distal symmetrical loss of sensory function in the lower extremities, presenting with spontaneous excruciating neuropathic pain, hyperalgesia, and allodynia that impairs quality of life. The current work aims to evaluate the neuroprotective potential of naringin (a citrus flavonoid) and examine its ability to improve Streptozotocin (STZ)-induced diabetic neuropathic pain by investigating its hypoglycemic, lipid-lowering, anti-inflammatory, and antioxidant effects. Methods: Diabetes was induced in 30 of 40 male Sprague-Dawley rats via a single STZ injection (45 mg/kg). Rats were divided into four groups: normal control, diabetic control, naringin-treated, and glimepiride-treated (positive control). After treatment, serum and brain tissues were collected to assess biochemical parameters. Pain-related behaviors were evaluated using hot plate, tail immersion, and von Frey filament tests. Results: A significant increase in the serum levels of glucose, triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and nitric oxide, with a concomitant decrease in body weight, plasma insulin, and high-density lipoprotein-cholesterol, was observed in diabetic rats. Also, the brain level of malondialdehyde was increased, while that of reduced glutathione, glutathione peroxidase, catalase, and superoxide dismutase were markedly decreased. Furthermore, diabetic rats showed a marked increase in plasma levels of inflammatory cytokines including interleukin-6 and tumor necrosis factor-α. Moreover, hot plate, tail immersion, and von Frey tests revealed hyperalgesia in diabetic rats. Treatment with naringin and glimepiride reduced pain hypersensitivity, restored body weight, and nearly normalized the altered biochemical parameters, more significantly with naringin than with glimepiride. Conclusions: These results may highlight the potential effects of naringin as a therapeutic strategy for diabetes and its complications, including peripheral neuropathy.

Keywords

flavonoids / naringin / peripheral sensory neuropathy / hyperalgesia / oxidative stress

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