Ameliorative Potential of Morin in Streptozotocin-Induced Neuropathic Pain in Rats

Purpose: To investigate the protective effect of morin, a naturally occurring bioflavonoid of Moraceae family, in experimentally-induced diabetic neuropathy (DN) in rats.Methods: Diabetes was induced by a single injection (65 mg/kg, ip) of streptozotocin (STZ). Morin (15 and 30 mg/kg/day) oral treatment was started 3 weeks after diabetes induction and continued for 5 consecutive weeks. Pain threshold behavior tests were performed at the end of the treatment. In sciatic nerve, inflammatory cytokines (TNF-á, IL-1â, IL-6), nerve growth factor (NGF) and insulin growth factor (IGF-1) were determined using ELISA kits, while thiobarbituric acid reactive substances (TBARS),glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels were assessed.Results: Diabetic animals showed apparent decreased paw-withdrawal (39 %, p < 0.05) and tail-flick (31 %, p < 0.05) latency as compared with control group. All the measured biomarkers were altered (p < 0.05 to 0.001) in diabetic rats compared with control non-diabetic animals. Morin treatment attenuated hyperalgesia and analgesia (p < 0.05) respectively. Morin treatment of diabetic rats at both doses significantly decreased the levels of cytokines (p < 0.01), glucose (p < 0.01) and TBARS (p < 0.001), but increased NGF (p < 0.01), IGF-1 (p < 0.01) and GSH (p < 0.01) levels in sciatic nerves compared to untreated diabetic animals. Inhibited activities (U/mg protein) of SOD (1.08 ± 0.16) and CAT (2.77 ± 0.36) in sciatic nerve of diabetic rats also found corrections (2.09 ± 0.11, p < 0.01) and (4.53 ± 0.57, p < 0.01) after morin (30 mg/kg/day) treatment, compared with untreated diabetic animals.Conclusion: These findings demonstrate the protective effect of morin mediated through reduction of oxidative stress and inflammatory process, and suggest the therapeutic potential of morin in the attenuation of diabetic neuropathy.Keywords: Morin, Diabetes, Neuropathy pain, Oxidative stress, Anti-inflammator

Inhibition of Ethanol-Induced Gastric Mucosal Damage by Carvedilol in Male Wistar Albino Rats: Possible Biochemical Changes

The effect of acute carvedilol (a third-generation nonselective P-blocker) pretreatment on gastric mucosal injury induced by 80% ethanol was investigated in male Wistar albino rats. The effects caused by pylorous ligation, accumulated gastric acid secretions and ethanol-induced changes in gastric mucus secretions, levels of proteins, nucleic acid, malondialdehyde (MDA) and non-protein sulfhydryl groups (NP-SH) in the stomach wall were investigated. The gastric ulcers were induced by administration of 1 mL of 80% ethanol, as a necrotizing agent into the stomach. Carvedilol pretreatment at two oral doses of 30 and 60 mg kg(-1) body weight were found to protect against the ulcerogenic effects of ethanol. Same dose regimen of carvedilol offered significant protection against ethanol-induced damage on the parameters evaluated for histopathology. Furthermore, the pretreatment afforded a significant inhibition of pylorous ligated accumulation of gastric acid secretions and ethanol-induced depletion of stomach wall mucus, nucleic acids, proteins and NP-SH contents. Only higher dose of carvedilol provided inhibition of ethanol-induced increase in MDA concentration. The protective effects of carvedilol against gastric secretion or damage to the gastric-wall mucosa may be mediated through its effects on mucus production and NP-SH concentrations, possible free-radical scavenging ability and/or cytoprotective properties

Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats

To investigate whether carnitine deficiency is a risk factor during the development of diethylnitrosamine (DENA)-induced hepatic carcinogenesis. METHODS: A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each group. Rats in group I (control group) received a single intraperitoneal (i.p.) injection of normal saline. Animals in group 2 (carnitine-supplemented group) were given L-carnitine (200 mg/kg per day) in drinking water for 8 wk. Animals in group 3 (carnitine-depleted group) were given D-carnitine (200 mg/kg per day) and mildronate (200 mg/kg per day) in drinking water for 8 wk. Rats in group 4 (DENA group) were injected with a single dose of DENA (200 mg/kg, i.p.) and 2 wk later received a single dose of carbon tetrachloride (2 mL/kg) by gavage as 1:1 dilution in corn oil. Animals in group 5 (DENA-carnitine depleted group) received the same treatment as group 3 and group 4. Rats in group 6 (DENA-carnitine supplemented group) received the same treatment as group 2 and group 4.RESULTS: Administration of DENA resulted in a significant increase in alanine transaminase (ALT), gamma-glutamyl transferase (G-GT), alkaline phosphatase (ALP), total bilirubin, thiobarbituric acid reactive substances (TBARS) and total nitrate/ nitrite (NOx) and a significant decrease in reduced glutathione (GSH), glutathione peroxidase (GSHPx), catalase (CAT) and total carnitine content in liver tissues. In the carnitine-depleted rat model, DENA induced a dramatic increase in serum ALT, G-GT, ALP and total bilirubin, as well as a progressive reduction in total carnitine content in liver tissues. Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes, TBARS and NOx, and a decrease in total carnitine, GSH, GSHPx, and CAT induced by DENA, compared with the control values. Histopathological examination of liver tissues confirmed the biochemical data, where L-carnitine prevented DENA-induced hepatic carcinogenesis while D-carnitine-mildronate aggravated DENA-induced hepatic damage.CONCLUSION: Data from this study suggest for the first time that: (1) carnitine deficiency is a risk factor and should be viewed as a mechanism in DENA-induced hepatic carcinogenesis; (2) oxidative stress plays an important role but is not the only cause of DENA-induced hepatic carcinogenesis; and (3) long-term L-carnitine supplementation prevents the development of DENA-induced liver cancer. (C) 2009 The WIG Press and Baishideng. All rights reserved

Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats

AIM: To investigate whether carnitine deficiency is a risk factor during the development of diethylnitrosamine (DENA)-induced hepatic carcinogenesis. METHODS: A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each group. Rats in group I (control group) received a single intraperitoneal (i.p.) injection of normal saline. Animals in group 2 (carnitine-supplemented group) were given L-carnitine (200 mg/kg per day) in drinking water for 8 wk. Animals in group 3 (carnitine-depleted group) were given D-carnitine (200 mg/kg per day) and mildronate (200 mg/kg per day) in drinking water for 8 wk. Rats in group 4 (DENA group) were injected with a single dose of DENA (200 mg/kg, i.p.) and 2 wk later received a single dose of carbon tetrachloride (2 mL/kg) by gavage as 1:1 dilution in corn oil. Animals in group 5 (DENA-carnitine depleted group) received the same treatment as group 3 and group 4. Rats in group 6 (DENA-carnitine supplemented group) received the same treatment as group 2 and group 4.RESULTS: Administration of DENA resulted in a significant increase in alanine transaminase (ALT), gamma-glutamyl transferase (G-GT), alkaline phosphatase (ALP), total bilirubin, thiobarbituric acid reactive substances (TBARS) and total nitrate/ nitrite (NOx) and a significant decrease in reduced glutathione (GSH), glutathione peroxidase (GSHPx), catalase (CAT) and total carnitine content in liver tissues. In the carnitine-depleted rat model, DENA induced a dramatic increase in serum ALT, G-GT, ALP and total bilirubin, as well as a progressive reduction in total carnitine content in liver tissues. Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes, TBARS and NOx, and a decrease in total carnitine, GSH, GSHPx, and CAT induced by DENA, compared with the control values. Histopathological examination of liver tissues confirmed the biochemical data, where L-carnitine prevented DENA-induced hepatic carcinogenesis while D-carnitine-mildronate aggravated DENA-induced hepatic damage.CONCLUSION: Data from this study suggest for the first time that: (1) carnitine deficiency is a risk factor and should be viewed as a mechanism in DENA-induced hepatic carcinogenesis; (2) oxidative stress plays an important role but is not the only cause of DENA-induced hepatic carcinogenesis; and (3) long-term L-carnitine supplementation prevents the development of DENA-induced liver cancer. (C) 2009 The WIG Press and Baishideng. All rights reserved