Effects of cyanocobalamin and its combination with morphine on neuropathic rats and the relationship between these effects and thrombospondin-4 expression.

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.

Changes in tissue gadolinium biodistribution measured in an animal model exposed to four chelating agents.

PURPOSE: This study investigated the potential to reduce gadolinium levels in rodents after repetitive IV Gadodiamide administration using several chelating agents. MATERIALS AND METHODS: The following six groups of rats were studied. Group 1: Control; Group 2: Gadodiamide only; Group 3: Meso-2,3-Dimercaptosuccinic acid (DMSA) + Gadodiamide; Group 4: N-Acetyl-L-cysteine (NAC) + Gadodiamide; Group 5: Coriandrum sativum extract + Gadodiamide; and Group 6: Deferoxamine + Gadodiamide. Brain, kidney, and blood samples were evaluated via inductively coupled plasma mass spectrometry. The brain was also evaluated histologically. RESULTS: Kidney gadolinium levels in Groups 4 and 5 were approximately double that of Group 2 (p = 0.033 for each). There was almost no calcification in rat hippocampus for Group 4 rodents when compared with Groups 2, 3, 5 and 6. CONCLUSION: Our preliminary study shows that excretion to the kidney has a higher propensity in NAC and Coriandrum sativum groups. It may be possible to change the distribution of gadolinium by administrating several agents. NAC may lower Gadodiamide-induced mineralization in rat hippocampus.

Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats.

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-1ß, 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.

The effect of platelet-rich plasma on motility changes in experimental caustic esophageal burn.

BACKGROUND: Besides stricture formation, diminished esophageal motility after caustic esophageal burns also plays a role in the deterioration of the clinical course. In this study, we aimed to investigate the effect of caustic burn on the esophageal contractions and the effect of platelet-rich plasma (PRP) on these changes. METHODS: Twenty-one Wistar albino rats were divided into three groups [Sham operation (n = 8), caustic esophageal burn with NaOH (n = 6), PRP treatment after caustic burn (n = 7)]. After 3 weeks, esophagectomy was performed and contractions and EFS responses were evaluated in the organ bath. RESULTS: KCl- and acetylcholine-induced responses were reduced in the Burn group, but increased in Sham and PRP groups (p < 0.05). EFS responses were higher in Burn group compared to the other groups. Response with L-arginine was increased in Burn group, but decreased in PRP group. There was more decrease in the contraction in Sham and PRP groups compared to the Burn group after SNP (sodium nitroprusside) incubation (p < 0.05). L-NAME (Nω-Nitro-L-arginine methyl ester) did not change the EFS responses in the Burn group, but EFS responses were decreased significantly in Sham and PRP groups (p < 0.05). EFS responses were decreased in all groups, but more in the Sham and PRP groups after Y-27632 (Rho-kinase inhibitor) incubation (p < 0.05). CONCLUSIONS: 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.