Increased reactive oxygen species by the activation of NADPH oxidase (NOX) contributes to the development of diabetic complications. Apocynin, a NOX inhibitor, increases sciatic nerve conductance and blood flow in diabetic rats. We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level. Rat models of streptozotocin-induced diabetes were treated with apocynin (30 and 100 mg/kg per day, intragastrically) for 4 weeks. Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer. Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively. Streptozotocin injection reduced pain threshold in analgesimeter, but not in aesthesiometer. Apocynin treatment increased pain threshold dose-dependently. Western blot analysis showed an increase in catalase and NOX-p47phox protein expression in the spinal cord. However, protein expressions of neuronal and inducible nitric oxide synthase (nNOS, iNOS), superoxide dismutase, glutathion peroxidase, nitrotyrosine, tumor necrosis factor-α, interleukin-6, interleukin-1β, aldose reductase, cyclooxygenase-2 or MAC-1 (marker for increased microgliosis) in the spinal cord remained unchanged. Western blot analysis results also demonstrated that apocynin decreased NOX-p47phox expression at both doses and catalase expression at 100 mg/kg per day. Histochemistry of diabetic sciatic nerve revealed marked degeneration. nNOS and iNOS immunoreactivities were increased, while S-100 immunoreactivity (Schwann cell marker) was decreased in sciatic nerve. Apocynin treatment reversed these changes dose-dependently. In conclusion, decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss. Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.
For the first time, we demonstrated that both cholinergic and non-adrenergic non-cholinergic mechanisms are responsible for the altered motility in corrosive esophageal injury. Our results suggest that PRP treatment may be helpful in regulating the esophageal motility and decreasing altered contractions in corrosive burns. This effect may also contribute to the reduction of stricture formation, especially by reducing inappropriate contractions of the esophageal wall during the post-burn healing phase.
Background: Thrombospondin-4 (TSP4) upregulates in the spinal cord following peripheral nerve injury and contributes to the development of neuropathic pain (NP). We investigated the effects of cyanocobalamin alone or in combination with morphine on pain and the relationship between these effects and spinal TSP4 expression in neuropathic rats. Methods: NP was induced by chronic constriction injury (CCI) of the sciatic nerve. Cyanocobalamin (5 and 10 mg/kg/day) was administered 15 days before CCI and then for 4 and 14 postoperative days. Morphine (2.5 and 5 mg/kg/day) was administered only post-CCI. Combination treatment included cyanocobalamin and morphine, 10 and 5 mg/kg/day, respectively. All drugs were administered intraperitoneally. Nociceptive thresholds were detected by esthesiometer, analgesia meter, and plantar test, and TSP4 expression was assessed by western blotting and fluorescence immunohistochemistry. Results: CCI decreased nociceptive thresholds in all tests and induced TSP4 expression on the 4th postoperative day. The decrease in nociceptive thresholds persisted except for the plantar test, and the increased TSP4 expression reversed on the 14th postoperative day. Cyanocobalamin and low-dose morphine alone did not produce any antinociceptive effects. High-dose morphine improved the decreased nociceptive thresholds in the esthesiometer when administered alone but combined with cyanocobalamin in all tests. Cyanocobalamin and morphine significantly induced TSP4 expression when administered alone in both doses for 4 or 14 days. However, this increase was less when the two drugs are combined. Conclusions: The combination of cyanocobalamin and morphine is more effective in antinociception and partially decreased the induced TSP4 expression compared to the use of either drug alone.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.