The management of diabetic neuropathy (DN) is still a challenge for physicians. Hyperglycemia induced oxidative stress involves in the development of diabetic neuropathy, which could be reversed by supplementation of antioxidants. In the present study, it has targeted the oxidative stress mediated nerve damage in DN by using combined therapy of rutin (RT) and silymarin (SM). Diabetes was induced by single streptozotocin (STZ, 65 mg/kg i.p.) injection. The diabetic rats were treated daily with RT (100 mg/kg), SM (60 mg/kg) and RT (50 mg/kg) + SM (30 mg/kg) for 6 consecutive weeks. Pain-related behavior tests were performed including tail flick, paw-pressure analgesia and Rota-rod treadmill performance. Serum glucose, insulin, tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and interleukine-1β (IL-β) levels were estimated. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) were measured. Diabetic rats that developed neuropathy were revealed by decreased tail-flick latency, paw-withdrawal latency and motor coordination. RT (100 mg/kg/day) and SM (60 mg/kg/day) dosed to diabetic rats, ameliorated hyperalgesia, analgesia and led to improved motor coordination. However, the combined therapy of RT (50 mg/kg/day) with SM (30 mg/kg/day) showed more significant effects in these parameters. STZ significantly increased TBARS and decreased GSH levels in sciatic nerve whereas combined therapy of RT and SM produced higher significant protection compared to individual. Similarly, combined therapy showed more significant amelioration in decreased levels of SOD, CAT, GST, GS and GPx activities in sciatic nerve of diabetic rats. Present results concluded that the combined therapy of phenolic compounds such as RT and SM had higher protective effects than their individual supplementations against DM.
The study of the expression and the tissue distribution of the tyrosine kinase drug-target epidermal growth factor receptor (EGFR) is of interest in oncology as a marker of potential efficacy of treatment. It has been reported, however, that the response rates to anti-EGFR drugs are poorly linked to its expression. Clinical studies have also revealed a patient response correlation with the expression levels of two EGFR ligands; amphiregulin and epiregulin. Here, we report the development of a matrix-assisted laser desorption/ionisation mass spectrometry imaging methodology for the study of EGFR, epiregulin and amphiregulin distribution in formalin fixed paraffin embedded human placental tissue and a comparison to expression patterns obtained by immunohiostochemistry. Using on-tissue digests and imaging of specific peptides, the tissue distribution of these proteins has been obtained down to 30 microm spatial resolution.
The aim of the present study is to investigate the effect of rutin, a potent antioxidant and antiinflammatory compound on experimentally-induced diabetic neuropathy (DN) in male Wistar rats. In diabetic and normal rats, the pain-related behavior tests were performed before and after rutin (50 and 100 mg/kg/day for 6 weeks) treatments. In serum, fasting glucose, insulin, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were estimated and in sciatic nerve, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, and superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione-reductase (GR) and glutathione peroxidase (GSH-Px) activities were measured. Diabetic rats developed neuropathy which was apparent from decreased tail-flick and paw-withdrawal latencies and by following decrease in performance on Rota-Rod treadmill. Rutin treatments ameliorated the hyperalgesia, analgesia and improved motor coordination. Streptozotocin (STZ) significantly increased TBARS and decreased GSH levels in sciatic nerve where rutin treatment significantly protected those changes. In diabetic rats, SOD, CAT, GST, GSH-Px and GR activities were significantly inhibited. Rutin treatment significantly ameliorated decrease in antioxidant defense. Present results demonstrate protective effect of rutin in diabetic neuropathy through attenuation of oxidative stress and they suggest that rutin is a potential drug for the prevention of early diabetic-induced neuropathy.
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