Darshee Baxi

Therapy with methanolic extract of Pterocarpus marsupium Roxb and Ocimum sanctum Linn reverses dyslipidemia and oxidative stress in alloxan induced type I diabetic rat model.

Methanolic extracts of Pterocarpus marsupium Roxb (P. marsupium) and Ocimum sanctum Linn (O. sanctum) were prepared separately and then administered to both non-diabetic and alloxan induced diabetic adult female Wistar rats as a mixture of both at a dosage of 500mg/kg body weight, and its effect was checked on serum and tissue lipids together with corticosterone, estrogen and progesterone profile. Further, tissue load of metabolites (cholesterol), enzymatic and non-enzymatic antioxidant status together with lipid peroxidation levels and serum markers of hepatic and renal damage were also assessed. Results of the present study strongly support the possibility of this herbal combination in humans to meet the objective of achieving a holistic amelioration and cure of diabetes as, the herbal extract mixture of P. marsupium and O. sanctum has succeeded in not only rectifying dyslipidemia but also in restoring the endogenous antioxidant levels to the pre diabetic status. Herbal preparations are ideal candidates of choice and in this context, the present combination of P. marsupium and O. sanctum provides compelling evidence for a holistic efficacy in amelioration of associated diabetic manifestations/dysregulations.

Melatonin supplementation in rat ameliorates ovariectomy-induced oxidative stress.

ABSTRACT Objective The present study aims to determine the potential of melatonin supplementation in ameliorating tissue oxidative stress, elevated serum corticosterone and hepatic and renal dysfunction. Materials and methods Adult Wistar rats, either ovariectomized or sham-operated, served as experimental or control groups, respectively. Rats received either melatonin, estrogen, progesterone or a combination of melatonin and estrogen for a period of 15 days. Tissue oxidative stress, serum markers of hepatic and renal dysfunction and serum corticosterone level formed the parameters of assay in all groups at the end of the treatment schedule. Results Ovariectomized rats showed significant increases in levels of tissue lipid peroxidation, serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase, acid phosphatase and corticosterone and significant decrement in enzymatic and non-enzymatic antioxidant status. All parameters showed maximal reversal to control levels on supplementation with high-dose melatonin or estrogen + melatonin treatment. Conclusion Melatonin supplementation proved better than estrogen replacement therapy, with the higher dose being more effective in preventing ovariectomy-induced increases in oxidative stress and serum levels of marker parameters of hepatic and renal dysfunction and corticosterone titer. Overall, melatonin supplementation therapy qualifies as a more potent and safe alternative to estrogen replacement therapy in alleviating postmenopausal increases in oxidative stress and hepatic and renal dysfunction.

Melatonin supplementation therapy as a potent alternative to ERT in ovariectomized rats

ABSTRACT Aim To evaluate the efficacy of melatonin supplementation therapy as an alternative to estrogen replacement therapy in an ovariectomized rat model and to assess diabetogenic metabolic dysregulation caused by estrogen deficiency in postmenopausal individuals. Methods Ovariectomized adult Wistar rats were treated with either estrogen/progesterone, melatonin or a combination of estrogen and melatonin. Body weight gain, feed efficiency, serum glucose, insulin, glucose tolerance and insulin response, serum and tissue lipids, tissue glycogen contents and activities of glycogen phosphorylase and glucose-6-phosphatase were analyzed in all the experimental groups. Results Ovariectomized animals showed increased body weight gain, feed efficiency, fasting insulin resistance, greater area under curve for the glucose tolerance test, higher serum and tissue lipids and reduced glycogen content and insulin sensitivity. A low dose of melatonin was more efficient than estrogen in reversing all the ovariectomy-induced changes. The combination of estrogen + melatonin was found to be best in correcting glycemic dysregulation while high doses of melatonin could effectively regulate dyslipidemia. Conclusion The present study provides strong evidence for melatonin supplementation therapy to be more potent and effective in comparison to estrogen replacement therapy due to its single-handed ability to revert all the ovariectomy-induced changes. No reported side-effect or long-term effect of melatonin, against the known effects of estrogen replacement therapy, make it more attractive as a candidate to treat postmenopausal symptoms.

Plasticity changes in adult metabolic homeostasis and tissue oxidative stress: neonatal programming by corticosterone and melatonin as deprogrammer

Objective: To evaluate the long-term plasticity changes induced by neonatal corticosterone programming on adult metabolic status and the deprogramming effect of melatonin. Methods: Male and female Wistar rats were maintained under standard conditions and when mated females delivered pups, neonates of both sexes were separated and equal number of pups was assigned to lactating mothers. Pups treated with saline, corticosterone or a combination of corticosterone and melatonin from PND 2 to PND 14, were maintained until 120 days of age. Various serum and tissue parameters pertaining to glycaemic regulation, dyslipidemia, hepatic and renal distress and oxidative stress were analyzed in adult rats. Results: Neonatal corticosterone exposure induced dyslipidemia, increased fed and fasting glucose levels, insulin resistance, lipid peroxidation, serum levels of insulin, corticosterone and hepatic and renal dysfunction markers and decreased the levels of enzymatic and non-enzymatic antioxidants, relatively more in males. Melatonin proved as an effective deprogrammer of corticosterone induced plasticity changes. Conclusions: Neonatal corticosterone exposure induces long lasting effects on adult physiology and metabolism. Concurrent treatment with melatonin effectively deprograms the changes.

Prior cadmium exposure improves glucoregulation in diabetic rats but exacerbates effects on metabolic dysregulation, oxidative stress, and hepatic and renal toxicity

The present study was taken up to assess the role of subchronic exposure to an environmentally relevant dosage of cadmium in type l diabetes. Female rats of the Wistar strain were treated with cadmium (5.12 mg/kg body weight) for 45 days. On day 46, rats were made diabetic by alloxan. After 7 days, diabetes (i.e., animals with serum glucose greater than 300 mg/dL) in the alloxanized animals was confirmed and further experiments were conducted for 15 days. Cadmium pretreatment showed disturbed glucose homeostasis with attendant changes in carbohydrate metabolism, coupled with decrease in food and water intake. Disturbance in carbohydrate metabolism was indicated by altered tissue metabolite load, as marked by a decrease in protein and glycogen contents and increased cholesterol store. Poor glucose clearance subsequent to a glucose challenge under the glucose tolerance test was observed in these animals (0.48/min in control vs. 0.13/min in Cd animals). There was a significantly lower glucose elevation rate in the insulin response test subsequent to an insulin-induced decrease in glucose level in Cd-exposed animals. Elevated oxidative stress was marked by increased lipid peroxidation, decreased antioxidant (both nonenzymatic and enzymatic) levels, and serum markers of hepatic and renal damage. Decreased corticosterone levels, together with increased E2 and reduced P4 levels, were some of the hallmark changes in the serum hormone profile of Cd-exposed animals. Overall, the present results are novel and interesting to open more investigations on animal models of type 1 diabetes with a history of previous Cd exposure.

Neonatal corticosterone programs for thrifty phenotype adult diabetic manifestations and oxidative stress: countering effect of melatonin as a deprogrammer

Objective: The present study assesses the thrifty phenotype response of neonatal corticosterone programming to a diabetogenic challenge in adult rats and the role of melatonin as a deprogrammer. Methods: Neonates of both sexes, born of healthy male and female rats maintained under standard conditions of temperature and light, were separated and, equal number of pups was assigned to lactating mothers. Pups treated with either saline or corticosterone or, a combination of corticosterone and melatonin from postnatal day (PND) 2 to PND 14 and, at 120 days of age, six animals from each treatment group were rendered diabetic by alloxanization. Various serum and tissue parameters pertaining to glycaemic regulation, dyslipidemia, hepatic and renal distress and oxidative stress were analysed in adult rats of all groups. Results: The results indicate compromised feed efficiency, hyperglycaemia, hypoinsulinemia, decreased glycogen content, elevated serum and tissue lipids and serum markers of hepatic and renal stress, together with increased lipid peroxidation, and decreased levels of non-enzymatic and enzymatic antioxidants in corticosterone programmed diabetic animals than in the non-programmed diabetic rats. However, treatment with melatonin simultaneously prevented to a significant extent the alterations in carbohydrate and lipid metabolism and oxidative stress. Conclusions: Melatonin is a potent deprogrammer of neonatal corticosterone programming effects and the adult thrifty phenotype alteration to a diabetogenic challenge.

Antihyperglycaemic and renoprotective effect of Boerhaavia diffusa L. in experimental diabetic rats.

The present study evaluates the efficacy of ethanolic extract of Boerhaavia diffusa L (BD) administered orally at a dose of 500mg/kg body weight for a period of 30 days to alloxanized diabetic rats and its efficacy compared with the standard hypoglycaemic drug metformin. Diabetic animals showed glycemic dysregulation, altered ionic balance, increased levels of serum markers of kidney function, and reduced Na+-K+ ATPase activity and endogenous antioxidant status. Administration of BD not only maintained the ionic balance and renal Na+-K+ ATPase activity but also significantly minimized diabetic hyperglycaemia. The renal antioxidant status (GPx, Catalase, SOD and GSH) remained in the near normal range and LPO level lower than the non-diabetic level. These effects are comparable to the changes brought about by metformin treatment and even better. Over all, the present study provides evidence for BD to be a potent renoprotective and antihyperglycaemic agent in diabetic animals.

Melatonin protects against chromium (VI) induced hepatic oxidative stress and toxicity: Duration dependent study with realistic dosage

Abstract The present study was undertaken to assess the degree of oxidative stress and toxic effects induced by chromium on hepatic tissue in male Wistar rats exposed to a realistic dosage of Cr(VI) (20 mg/kg/b.w./day) through drinking water, based on the levels of these metals found in the environment, for a duration of 15, 30 and 60 days. The protective effect of melatonin (10 mg/kg) was also studied by simultaneous administration with the metal. Levels of enzymatic and non-enzymatic antioxidants as well as lipid peroxidation were assessed. There was a significant decrease in enzymatic as well as non-enzymatic antioxidants and an increase in the lipid peroxidation level, which were prevented and maintained at near-normal levels by the administration of melatonin in all treatment periods. Metal accumulation was maximal at 15 days, with gradual decreases till 60 days. Histopathological observations also demonstrated the fact that Cr (VI) exposure leads to cytological lesions in the hepatic tissue promoting cellular necrotic/apoptotic changes, while melatonin was able to counteract insults induced by Cr (VI) at all treatment periods. It also prevented alterations in insulin and glucose levels. Overall, the present study suggests a duration-dependent effect of Cr on hepatic oxidative stress and cytotoxicity and shows the potent activity of melatonin in preventing the negative effects of Cr (VI).