Elaeocarpus ganitrus: its beneficial antiparkinsonian effect in MPTP induced motor and non-motor impairments in mice.

Aim: Elaeocarpus ganitrus (Family: Elaeocarpaceae), has shown beneficial role in the treatment of depression, convulsions and asthma. This study was undertaken to evaluate the antiparkinson effect of E.ganitrus. Materials and methods: Swiss albino mice of either sex were divided into 06 groups (n =12). 1st group mice were given 0.5% carboxy methyl cellulose (orally), 2nd group were administered MPTP (2 doses, each dose 20 mg/kg at 2 hr. interval, i.p.). Whereas 3rd, 4th and 5th groups - were administered with E. ganitrus (100, 200, and 400 mg/kg/day, orally), respectively, along with MPTP. Group 6- received Levodopa (30mg/kg, i.p,) along with MPTP. To evaluate anti-Parkinson effect, hanging wire test, tardive dyskinesia test and elevated plus maze test were performed on the1st day and on 8 th day. One way ANOVA followed by post-hoc Tukey test, with p<0.05 was considered statistical significant. Results: E.ganitrus (200 and 400 mg/kg, p.o.) was found to increase the hanging time significantly (p <0.001) in hanging wire test and significantly decreased (p <0.001) the Vacuous Chewing Movements (VCMs) in tardive dyskinesia test as compared to MPTP group. E.ganitrus (200 and 400 mg/kg, p.o.) was found to significantly increase (p <0.001) the no. of entries and time spent in open arm and significantly decreased the no. of entries and time spent in closed arm (p <0.001) compared to MPTP treated group. Conclusion: The results of the present study conclusively showed that E.ganitrus has beneficial effect in MPTP induced experimental model of Parkinson’s disease.

Oxidative stress and leukocyte migration inhibition response in cutaneous adverse drug reactions.

Background: Cutaneous adverse drug reactions (CADRs) may either be immunological or non-immunological. The precise mechanisms, however, are largely obscure. Other concomitant mechanisms may amplify and/or contribute to the severity and duration of a reaction. One such mechanism could be oxidative stress, a state of imbalance between reactive oxygen species, and their subsequent detoxification by antioxidants. Aims: (a) to assess the oxidative stress status in the blood of cutaneous drug reaction patients by assaying for reduced glutathione (GSH) and malondialdehyde (MDA) levels, (b) to determine the leukocyte migration inhibition (LMI) response in these patients in response to the suspected drug (s), and (c) to look for the association between oxidative stress parameters and LMI. Methods: Ethical committee approval was obtained for this study. Fresh venous blood samples were obtained from the patients of CADRs (group A) during the acute phase of reaction and healthy control subjects (group B). MDA levels, a measure of oxidative lipid damage, and reduced GSH levels, a measure of anti-oxidant capacity, were assayed in the blood samples of both groups using spectrophotometry. LMI response was measured by challenging the patients' peripheral blood mononuclear cells with the suspected drug to confirm immunological perturbation. Results: Totally 66 participants, 33 cases in group A and equal number of controls in group B, were studied. The mean MDA levels were found to be raised (P < 0.001), but GSH levels were significantly reduced in group A when compared with group B (P = <0.001). LMI response against drug(s) was performed in 33 cases (group A), out of which 25 cases showed a positive LMI response as follows: fixed drug eruption (10/25), SJS (5/25), urticaria (3/25), exfoliative dermatitis (2/25), morbilliform rash (2/25), erythroderma (1/25), vasculitis (1/25), and dapsone syndrome (1/25). The mean MDA levels were found to be significantly higher in the LMI positive CADRs (P < 0.001) when compared with LMI-negative ones, while no significant difference was seen for GSH (P = 0.100). Furthermore, there was a significant positive correlation between MDA levels and LMI response (r = 0.831, P < 0.001). On the other hand, a negative but statistically insignificant correlation was found between GSH and LMI response (r = -0.248, P = 0.271). Conclusion: CADR patients were found to be under oxidative stress based on MDA and GSH levels in the peripheral blood. There is a significant positive correlation of LMI response (against the causative drug) with MDA levels, which strongly associates oxidative stress with the immunopathogenesis in CADRs.

Ameliorative role of atorvastatin on methionine-induced hyperhomocysteinemia and hematological changes in albino rats.

Methionine (1g/kg, po) administration to pathogenic control rats for 30 days significantly increased the levels of homocysteine, total cholesterol (TC), low density lipoprotein (LDL-C), very low density lipoprotein (VLDL-C) and triglycerides (TGs) and decreased the levels of high density lipoprotein (HDL-C) in serum. Hematological observations of the peripheral blood smears of pathogenic rats fed with methionine also showed crenation of RBCs cell membrane and significant increase in total leukocyte count, differential leukocyte count and platelet counts with significant decrease in the mean hemoglobin levels as compared to vehicle control rats. Administration of atorvastatin (0.2 mg/kg/po) to hyperhomocysteinemic rats significantly decreased the levels of homocysteine, TC, TGs, LDL-C and VLDL-C and increased the levels of HDL-C in serum. The present results provide clear evidence that oral treatment with atorvastatin exhibit homocysteine and lipid lowering activity and also reversal of hematological changes induced by methionine in albino rats.

Comparative effect of Ocimum sanctum, Commiphora mukul, folic acid and ramipril on lipid peroxidation in experimentally-induced hyperlipidemia.

Treatment with C. mukul and O. sanctum, showed a significant decrease in cholesterol and triglyceride levels respectively. O. sanctum also significantly increased serum HDL-cholesterol compared to control. Serum MDA levels were significantly reduced in all the treated groups compared to control suggesting that each of the drugs under study were effective in their free radical scavenging action. Erythrocyte SOD activity was increased in all the treatment groups with C. mukul showing the maximum effect followed by O. sanctum, folic acid and ramipril. The erythrocyte CAT activity was significantly increased in all the drug treated groups with maximum increase seen in O. sanctum and ramipril treated groups, whereas lesser effects were observed with C. mukul and folic acid groups. Thus, the indigenous drugs, C. mukul and O. sanctum had beneficial effect on hypercholesterolemic rabbit model, both in terms of lipid profile as well as antioxidant potential. Ocimum sanctum was found to be the most promising of all the drugs. Moreover, it could be hypothesized that these plant products along with folic acid and ramipril can be explored for synergistic effect for treatment for hypercholesterolemic conditions.

Modulation of Oxidative Stress, Serum Lipids and Renal Dysfunction by Benazepril in Diabetes Mellitus.

Present study assessed the effect of benazepril on oxidative stress, serum lipids and renal dysfunction in alloxan induced diabetic rabbits. Benazepril reversed the increase in level of malondialdehyde and decrease in level of glutathione and superoxide dismutase activity caused by induction of diabetes. It also had a beneficial effect on diabetic dyslipidemia as manifested by elevation in serum HDL cholesterol. However, it had no effect on serum LDL, total cholesterol or triglycerides. Benazepril also attenuated the renal dysfunction induced by diabetes. It resulted in significant reduction in blood urea, serum creatinine and urine albumin excretion as compared to diabetic control rabbits. Further, kidney weight was significantly less in benazepril treated rabbits as compared to diabetic rabbits. To conclude, benazepril was found to be effective in preventing the oxidative stress and renal dysfunction as well as beneficial on serum lipids in experimentally-induced diabetes mellitus.

Peripheral interaction of opioid and nmda receptors in inflammatory pain in rats.

Both opioid and NMDA receptors have been known to be involved in pain processing in the central nervous system as well as in the periphery. The effect of drugs acting on opioid and NMDA receptors, and their role in modulation of pain response was observed in the formalin model of inflammatory pain in rats. We have demonstrated that morphine has significant antinociceptive effect in the formalin model and this effect was enhanced when given in combination with ketamine. We have also reported modulation of pain response when naloxone or NMDA were co-administered with morphine or ketamine in various combinations. A noteworthy observation in our study is that low dose naloxone when co-administered with ketamine and morphine, or with ketamine and NMDA, caused decrease in the pain response. These observations may suggest that low dose naloxone can cause modulation of opioid and NMDA receptors resulting in antinociceptive effect. Our study thus introduces a new concept of more than two drugs acting on opioid and NMDA receptors to modulate pain response.