Diosgenin inhibits ER stress-induced inflammation in aorta via iRhom2/TACE mediated signaling in experimental diabetic rats: An in vivo and in silico approach.

Hyperglycemia, hyperlipidemia, and atherosclerotic lesions may cause inflammation, which leads to chemokine production and changes in vascular responses. Hyperglycemia can impair normal protein folding by producing reactive oxygen species (ROS) and interacting with various signaling molecules, resulting in the activation of ER stress responses, that stimulates NF-kB, which regulates the expression of numerous genes involved in inflammation and vascular remodeling. Our previous studies have shown that diosgenin has a protective effect against streptozotocin (STZ) - induced oxidative damage in rat aorta. However, the therapeutic role of diosgenin on iRhom2/TACE signaling which has primarily been linked to the endoplasmic reticulum (ER)-stress induced inflammation is unknown. Diosgenin was administered (40 mg/kg b. wt, orally, for 4 weeks) to STZ-induced male albino rats. Fasting plasma glucose, blood pressure, nitrite level, lipid profile, and lipoprotein were assessed. Serum insulin and pro-inflammatory markers were analyzed using ELISA, mRNA and protein expression of iRhom2/TACE signaling molecules were analyzed using RT-PCR and western blotting analysis respectively. In silico study was also performed to find out the possible binding affinity of diosgenin with the ER stress signaling molecules. Through regulation of the iRhom2/TACE signaling molecules, diosgenin lowered dyslipidemia, hypertension, and pro-inflammatory cytokines (TNF-α, IL-1, IL-6, and IL-4) in the aorta of STZ induced diabetic rats. Results of molecular docking analysis also confirmed the potential binding interaction with iRhom2/TACE and TNF- α. These in silico and in vivo results indicated that a change in lipid profile and hypertension led to diabetes-related inflammation by promoting ER stress and, as a result, accelerating the aorta by generating proinflammatory cytokines and lipid deposition. This study concludes that diosgenin attenuates ER stress-induced inflammation in diabetic rat aorta by modulating the expression of pro-inflammatory, iRhom2/TACE mediated mechanism and hence diosgenin can be a therapeutic drug for the treatment of diabetes-induced inflammation.

Myrtenal attenuates oxidative stress and inflammation in a rat model of streptozotocin-induced diabetes.

The present study was aimed to investigate the effect of myrtenal on diabetes-associated oxidative stress, lipid peroxidation (LPO), and inflammation using a rat model of streptozotocin (STZ)-induced diabetes. Following the induction of diabetes in male Wistar rats using STZ (40 mg/kg body weight), myrtenal (80 mg/kg body weight) was administered orally to diabetic rats for four weeks and then sacrificed to harvest tissues. We measured the levels of antioxidants, LPO, and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and the p65 subunit of nuclear factor-kappa B (NF-kB p65). Diabetic rats revealed increased levels of LPO, proinflammatory cytokines, and NF-kB p65, and decreased levels of antioxidants in the liver and pancreas. Supplementation with myrtenal significantly attenuated the diabetes-induced changes in the liver and pancreas of diabetic rats. Our findings suggest that myrtenal may serve as an antioxidant and anti-inflammatory agent against diabetes-associated oxidative stress and inflammation.HighlightsOral administration of myrtenal improved the antioxidant status in the liver and pancreas of diabetic rats.Myrtenal treatment diminished inflammation in the liver and pancreas of diabetic rats.Myrtenal supplementation averts oxidative stress and inflammation in diabetic rats.Myrtenal could serve as a potent antioxidant and anti-inflammatory agent in the management of diabetes.

Antihyperlipidemic effect of tyrosol, a phenolic compound in streptozotocin-induced diabetic rats.

We investigated the antihyperlipidemic effects of tyrosol in streptozotocin (STZ)-induced diabetic rats. Rats were injected intraperitoneally with STZ (40 mg/kg), and these established experimental rats were treated with tyrosol (20 mg/kg) and glibenclamide (600 µg/kg) for 45 days. The observed results revealed that tyrosol treatment significantly reduced plasma glucose, plasma, and liver total cholesterol, triglycerides, free fatty acids, phospholipids, plasma low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, and significantly increased plasma insulin and high-density lipoprotein cholesterol in STZ-induced diabetic rats. The activity of 3-hydroxy 3-methylglutaryl coenzyme A reductase significantly reduced in the liver, whereas the activities of lipoprotein lipase and lecithin cholesterol acyltransferase were significantly increased in the plasma of tyrosol treated STZ-induced diabetic rats. Histological examination showed that tyrosol treatment remarkably reduced lipid accumulation in the liver of STZ-induced diabetic rats. The present study revealed that tyrosol exhibits potent antihyperlipidemic effects in STZ-induced diabetic rats.

In-vivo and In-vitro Antioxidant Activity of Troxerutin on Nickel Induced Toxicity in Experimental Rats.

The aim of the present study was to evaluate the effect of troxerutin (TXN) on Nickel (Ni) toxicity by using rats and in-vitro model. Ni toxicity induced in male albino wistar rats (20 mg/kg body weight (b.w) was administered orally for 20 days). TXN was administered orally (100 mg/kg (b.w) for 20 days with administration of Ni. The toxic effect of Ni and the action of TXN was measure by determining the lipid peroxidation markers and antioxidant levels in plasma and various in-vitro antioxidant systems. TXN exhibited a significant (p < 0.05) antioxidant activity in Ni induced toxicity by reversing the changes observed in TBARS, HP, Vitamin C, E and GSH. The free radical scavenging properties of TXN at different concentrations (10-50ug/mL) were investigated with various in-vitro methods such as 2, 2'-diphenyl-1- picrylhydrazyl radical (DPPH), 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS•+), hydroxyl radical, superoxide anion scavenging activity and reducing power. Among the different concentrations, 50 µg/mL of TXN was more effective compared to other concentrations in all in-vitro assays. The above study conclude that TXN possesses potent in-vivo and in-vitro antioxidant activity with effective free radical scavenger for potential therapeutic value.

Beneficial Protective Effect of Troxerutin on Nickel-Induced Renal Dysfunction in Wistar Rats.

Nickel (Ni) is an important environmental toxicant that can cause cancer and cardiovascular disease. The aim of this study was to examine the protective effects of troxerutin (Txn) Ni-induced renal dysfunction in rats using biochemical and histopathological approaches. Nickel (20 mg/kg body weight [b.w.]/day) was administered intraperitoneally (i.p.) for 20 days. Renal damage from Ni toxicity was evident from the changed levels of serum and urinary markers in Ni-treated rats. The levels of lipid peroxidation markers also significantly increased, while the levels of nonenzymatic and enzymatic antioxidants significantly decreased in the kidney of Ni-intoxicated rats. Troxerutin was administered orally (100 mg/kg b.w.) for 20 days along with Ni, resulting in a reversal of Ni-induced biochemical changes in kidney accompanied by a significant decrease in lipid peroxidation and an increase in the level of renal antioxidant defense system. Histopathological studies in the kidneys of rats also showed that troxerutin (100 mg/ kg b.w.) markedly reduced the toxicity of Ni and preserved the normal histological architecture of the renal tissue. The present study results suggest the nephroprotective potential of Txn in Ni toxicity, which might be due to its antioxidant and metal-chelating properties.

Molecular Action of Inflammation and Oxidative Stress in Hyperglycemic Rats: Effect of Different Concentrations of Pterocarpus marsupiums Extract.

Pterocarpus marsupium (Roxb.) (family Fabaceae) is widely used as a traditional medicine to treat various diseases, including diabetes. However, the molecular mechanism of Pterocarpus marsupium has not been investigated. Two fractions (2.5% and 5%) of extract from the medicinal plant Pterocarpus marsupium (PME) were administered in a dose-dependent manner in rats with streptozotocin-induced (45 mg/kg body weight) type 2 diabetes. Each fraction of PME was administered intragastrically at a dose of 50, 100, and 200 mg/kg body weight for 45 days. The effective dose 200 mg/kg body weight of 5% fraction was more pronounced in reducing the levels of blood glucose (95.65 mg/dL) and glycosylated hemoglobin (HbA1c) (0.41 mg/g Hb) and increasing the plasma insulin (16.20 µU/mL) level. The altered activities of the key enzymes of lipid metabolism along with the lipid profile in diabetic rats were significantly reverted to near normal levels by the administration of PME 5% 200 mg/kg body weight fraction. PME (200 mg/kg body weight) has the ability to reduce oxidative stress and inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) Interleukin-6 (IL-6) messenger ribonucleic acid (mRNA), as well as protein expression and apoptotic marker, such as caspase-3 enzyme, in diabetic hepatic tissue. Biochemical findings were also supported by histological studies, such as improvement in pancreas and liver. Pterocarpus marsupium could effectively reduce the inflammation and hyperglycemic condition in diabetic rats; hence, it could be a useful tool in the management of diabetes.

Modulatory effects of naringin on hepatic key enzymes of carbohydrate metabolism in high-fat diet/low-dose streptozotocin-induced diabetes in rats.

We evaluated the modulatory effects of naringin on altered hepatic key enzymes of carbohydrate metabolism in high-fat diet/low-dose streptozotocin-induced diabetic rats. Oral treatment of naringin at a doses of 20, 40 and 80 mg/kg body weight to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, blood glycosylated hemoglobin and increase in the levels of plasma insulin and blood hemoglobin. The altered activities of the hepatic key enzymes of carbohydrate metabolism such as hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase, glycogen phosphorylase and glycogen content of diabetic rats were significantly reverted to near normal levels by the treatment of naringin in a dose-dependent manner. Naringin at a dose of 80 mg/kg body weight showed the highest significant effect than the other two doses (20 and 40 mg/kg). Further, immunohistochemical observation of pancreas revealed that naringin-treated diabetic rats showed the increased number of insulin immunoreactive ß-cells, which confirmed the biochemical findings. These findings revealed that naringin has potential antihyperglycemic activity in high-fat diet/low-dose streptozotocin-induced diabetic rats.

Beneficial effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats.

CONTEXT: Olive oil is the major source of tyrosol which is a natural phenolic antioxidant. Olive oil constitutes a major component of the Mediterranean diet that is linked to a reduced incidence of chronic diseases. OBJECTIVE: This study evaluates the effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Diabetes mellitus was induced in male Wistar rats by streptozotocin (40 mg/kg body weight). These rats were administered tyrosol (20 mg/kg body weight) and glibenclamide (600 µg/kg body weight) orally daily for 45 days. Plasma glucose, plasma insulin, glycoprotein components such as hexose, hexosamine, sialic acid and fucose in the plasma, liver and kidney, and histopathogy of tissues were analyzed. RESULTS: Diabetic rats revealed significant (p < 0.05) increase in the levels of glucose, hexose, hexosamine, sialic acid and fucose (277.17, 152.45, 100.43, 79.69 and 49.29 mg/dL) in the plasma; decrease in the levels of palsma insulin (6.12 µU/mL) and sialic acid (4.36 and 5.03 mg/g) in the liver and kidney; significant (p < 0.05) increase in hexose (49.33 and 46.82 mg/g), hexosamine (22.68 and 33.20 mg/g) and fucose (31.63 and 32.44 mg/g) in the liver and kidney. Further, periodic acid-Schiff staining of tissues revealed positive-stain accumulation in diabetic rats. Tyrosol treatment showed significant (p < 0.05) effects on all the biochemical parameters and histopathology studied in streptozotocin- nduced diabetic rats. Also, the in vitro study revealed the antioxidant effect of tyrosol. DISCUSSION AND CONCLUSIONS: Thus, tyrosol protects streptozotocin-induced diabetic rats from the altered glycoprotein components. Further, this study can be extrapolated to humans.

Protective Role of Tetrahydrocurcumin: an Active Polyphenolic Curcuminoid on Cadmium-InducedOxidative Damage in Rats.

In the present work, protective effect of tetrahydrocurcumin (THC) against oxidative damages in cadmium (Cd)-induced toxicity in rats was evaluated. Cd is an important environmental and industrial toxicant that affects almost all the organs, especially liver. Liver is the major organ responsible for the metabolism and the primary target for many toxic chemicals and drugs. Effect of THC, the curcumin-derived polyphenolic compound on Cd-induced oxidative stress and hepatic damage was evaluated using male albino Wistar rats. In Cd-administered rats (5 mg/kg body weight (b.w.), orally for 4 weeks), activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT) were significantly increased in serum with the elevated level of bilirubin. Red blood cells (RBC), haemoglobin contents and haematocrit values were also significantly decreased in Cd-treated rats. In addition, the levels of lipid peroxidation markers like thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LHP), protein carbonyl contents (PCC) and conjugated dienes (CD) were significantly increased followed by the significant decrease in the levels of reduced glutathione (GSH), total sulphydryl groups (TSH), ascorbic acid (vitamin C) and vitamin E in liver of Cd-administered rats. Oral administration of THC (20, 40 and 80 mg/kg b.w.) followed by Cd for 4 weeks showed a significant restoration of the above changes to near normal. Histopathological changes observed in Cd intoxicated hepatic tissues were minimized on treatment with THC. This study suggests that THC at the dose of 80 mg/kg b.w. effectively subdues the Cd-induced toxicity and controls the free radical-induced liver damage in rats.

Protective Effect of Troxerutin on Nickel-Induced Testicular Toxicity in Wistar Rats.

Nickel (Ni)-induced oxidative damage is a serious problem that leads to reproductive system failure through testicular damage. The present investigation was carried out to determine the effect of troxerutin (Txn) on testicular toxicity induced by Ni in experimental rat testes. The oral administration of Txn (100 mg/kg body weight [bw]) showed a significant (p < 0.01) increase in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), reduced glutathione, ascorbate, total sulphydryl groups, and testis-organ weight. Subsequently, the administration of Txn also significantly reduced the accumulation of Ni, lipid peroxidation products, and protein carbonyl levels in Txn-treated animals. Testicular protection in the experimental animals by Txn is further substantiated by a remarkable reduction of Ni, which was revealed through testicular tissue histopathology. These studies suggest that Txn could prevent oxidative damage and testicular toxicity induced by Ni in experimental animals.

Myrtenal ameliorates hyperglycemia by enhancing GLUT2 through Akt in the skeletal muscle and liver of diabetic rats.

Insulin signaling pathway is an important role in glucose utilization in tissues. Our Previous study has established that myrtenal has antihyperglycemic effect against diabetic rats. The aim of this study was to explore the molecular mechanism of myrtenal in Streptozotocin-induced diabetic rats. Experimental diabetes was induced by single intraperitoneal injection of Streptozotocin (STZ) (40 mg/kg bw) in Wistar albino rats. Diabetic rats were administered myrtenal (80 mg/kg bw) for a period of 28 days. Diabetic rats showed an increased the levels of plasma glucose, decreased the levels of plasma insulin, down-regulation of insulin receptor substrate 2 (IRS2), Akt and glucose transporter 2 (GLUT2) in liver and insulin receptor substrate 2 (IRS2), Akt and glucose transporter 4 (GLUT4) protein expression in skeletal muscle. However, myrtenal treated diabetic rats revealed decreased the levels of plasma glucose, improved the plasma insulin levels, up-regulation of IRS2, Akt and GLUT2 in liver and IRS2, Akt and GLUT4 protein expression in skeletal muscle. The up-regulation of glucose transporters enhances the glucose uptake in liver and skeletal muscle. The histopathology and immunohistochemical analysis of the pancreas also corroborates with the above findings. Our findings suggest that myrtenal could be a potent phytochemical in the management of diabetes.

Trans-anethole, a terpenoid ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats.

Trans-anethole (TA), a terpenoid and a principle constituent of many essential oils from medicinal plants possess hypoglycemic and antioxidant activities. This study was undertaken to explore beneficial effects of TA on key enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced type 2 diabetic rats. Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg BW). TA was administered to diabetic rats at a dose of 20, 40 and 80 mg/kg BW for 45 days. However, the dose at 80 mg/kg BW, resulted in a significant reduction in the levels of plasma glucose, glycosylated haemoglobin (HbA1c) and increase in the levels of insulin and haemoglobin (Hb). Upon administration of TA, the altered levels of liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase) and gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-bisphosphatase) in the liver and kidney of diabetic rats significantly reverted to near normal levels. In addition to this, TA also improved the hepatic and muscle glycogen content in diabetic rats. The histological studies showed the ameliorative effect of TA on the ß-cells of pancreas in diabetic rats. The results were compared with glibenclamide, a standard oral hypoglycemic drug. These encouraging findings suggest that TA may be used as a propitious bioactive compound in the development of therapeutic agents against type 2 diabetes mellitus.

Tyrosol, a phenolic compound, ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats.

The present study was designed to evaluate the effects of tyrosol, a phenolic compound, on the activities of key enzymes of carbohydrate metabolism in the control and streptozotocin-induced diabetic rats. Diabetes mellitus was induced in rats by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight). Experimental rats were administered tyrosol 1 ml intra gastrically at the doses of 5, 10 and 20mg/kg body weight and glibenclamide 1 ml at a dose of 600 µg/kg body weight once a day for 45 days. At the end of the experimental period, diabetic control rats exhibited significant (p<0.05) increase in plasma glucose, glycosylated hemoglobin with significant (p<0.05) decrease in plasma insulin, total hemoglobin and body weight. The activities of key enzymes of carbohydrate metabolism such as phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase were significantly (p<0.05) increased and the activities of hexokinase and glucose-6-phosphate dehydrogenase were significantly (p<0.05) decreased in the liver and kidney of diabetic control rats. Further, antioxidants were lowered in diabetic control rats. A significant (p<0.05) decline in glycogen level in the liver and muscle and glycogen synthase activity in the liver and a significant (p<0.05) increase in the activity of liver glycogen phosphorylase were observed in diabetic control rats compared to normal control rats. Oral administration of tyrosol to diabetic rats reversed all the above mentioned biochemical parameters to near normal in a dose dependent manner. Tyrosol at a dose of 20mg/kg body weight showed the highest significant effect than the other two doses. Immunohistochemical staining of pancreas revealed that tyrosol treated diabetic rats showed increased insulin immunoreactive ß-cells, which confirmed the biochemical findings. The observed results were compared with glibenclamide, a standard oral hypoglycemic drug. The results of the present study suggest that tyrosol decreases hyperglycemia, by its antioxidant effect.

Protective effects of hesperidin on oxidative stress, dyslipidaemia and histological changes in iron-induced hepatic and renal toxicity in rats.

The present study was to evaluate the protective role of hesperidin (HDN) against iron-induced hepatic and renal toxicity in rats. Administration of iron (30 mg/kg body weight) intraperitoneally for 10 days, the levels of serum hepatic markers, renal functional markers, lipid profile, lipid peroxidation markers and iron concentration in blood were significantly (p < 0.05) increased. The toxic effect of iron was also indicated by significant (p < 0.05) decrease in the levels of plasma, liver and kidney of enzymatic and non-enzymatic antioxidants. Administration of hesperidin at different doses (20, 40 and 80 mg/kg body weight) significantly (p < 0.05) reversed the levels of serum hepatic markers, renal functional markers, lipid profile, lipid peroxidation markers, restored the levels of hepatic, renal enzymatic antioxidants and non-enzymatic antioxidants with decrease in iron concentration in blood. Hesperidin at a dose of 80 mg/kg body weight exhibits significant protection on hepatic and renal when compared with other two doses (20 and 40 mg/kg body weight). All these changes were corroborating by histological observations of liver and kidney. This study demonstrated the protective role of hesperidin in reducing toxic effects of iron in experimental rats.

Histopathological findings of the pancreas, liver, and carbohydrate metabolizing enzymes in STZ-induced diabetic rats improved by administration of myrtenal

This study aims to evaluate the efficacy of myrtenal, a natural monoterpene, for its antihyperglycemic effects and beta cell protective properties in streptozotocin (STZ)-induced diabetic rats. Oral administration of myrtenal at doses of 20, 40, and 80 mg/kg body weight to diabetic rats for 28 days resulted in a significant reduction (P < 0.05) in the levels of plasma glucose, glycosylated hemoglobin (HbA1c), and an increase in the levels of insulin and hemoglobin (Hb). Protection of body weight loss of diabetic rats by myrtenal was noted. The altered activities of the key metabolic enzymes involved in carbohydrate metabolism such as hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, and hepatic enzymes AST, ALT, and ALP levels of diabetic rats were significantly improved by the administration of myrtenal in STZ-induced diabetic rats. Moreover, myrtenal treatment improved hepatic and muscle glycogen content in diabetic rats. Histopathological studies further revealed that the reduced islet cells were restored to near-normal conditions on treatment with myrtenal in STZ-induced diabetic rats. An alteration in liver architecture was also prevented by myrtenal treatment. Our results suggest that myrtenal possess antihyperglycemic and beta cell protective effects. Hence, myrtenal could be considered as a potent phytochemical for development as a new antidiabetic agent (AU)

Histopathological findings of the pancreas, liver, and carbohydrate metabolizing enzymes in STZ-induced diabetic rats improved by administration of myrtenal.

This study aims to evaluate the efficacy of myrtenal, a natural monoterpene, for its antihyperglycemic effects and ß cell protective properties in streptozotocin (STZ)-induced diabetic rats. Oral administration of myrtenal at doses of 20, 40, and 80 mg/kg body weight to diabetic rats for 28 days resulted in a significant reduction (P < 0.05) in the levels of plasma glucose, glycosylated hemoglobin (HbA1c), and an increase in the levels of insulin and hemoglobin (Hb). Protection of body weight loss of diabetic rats by myrtenal was noted. The altered activities of the key metabolic enzymes involved in carbohydrate metabolism such as hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, and hepatic enzymes AST, ALT, and ALP levels of diabetic rats were significantly improved by the administration of myrtenal in STZ-induced diabetic rats. Moreover, myrtenal treatment improved hepatic and muscle glycogen content in diabetic rats. Histopathological studies further revealed that the reduced islet cells were restored to near-normal conditions on treatment with myrtenal in STZ-induced diabetic rats. An alteration in liver architecture was also prevented by myrtenal treatment. Our results suggest that myrtenal possess antihyperglycemic and ß cell protective effects. Hence, myrtenal could be considered as a potent phytochemical for development as a new antidiabetic agent.

Ameliorating effects of troxerutin on nickel-induced oxidative stress in rats.

OBJECTIVE: This study investigates the effects of troxerutin on nickel (Ni)-induced oxidative stress in rats. METHODS: Nickel as nickel sulfate (20 mg/kg body weight (b.w.)) was administered intraperitoneally for 20 days to induce toxicity in the subject rats. The levels of stress markers AST, ALT, ALP, LDH, and GGT in the hepatic tissue were significantly increased while a decrease in the levels of enzymic and non-enzymic antioxidants was observed in Ni intoxicated rats. RESULTS: Oral administration of troxerutin along with Ni for 20 days in a dose-dependent manner significantly reverted the stress markers in the liver tissue to near normal level. Troxerutin exhibited significant protection at 100 mg/kg b.w. Histopathological studies also supported the above findings. CONCLUSIONS: Thus, we conclude that troxerutin preserved the histo-architecture and ameliorated stress markers in the liver tissue of Ni-intoxicated rats.

Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats.

The present study was designed to investigate the beneficial role of diosgenin on oxidative stress markers and histopathological changes in aorta of streptozotocin induced diabetic rats. Diabetes was induced in experimental rats by a single intraperitoneal injection of streptozotocin (55 mg/kg body weight (b.w.)). From the sixth week, experimental rats received diosgenin at different doses (10, 20 and 40 mg/kg b.w.) once daily for 4 weeks. At the end of the experimental periods, diabetic rats exhibited significant increase in the levels of plasma glucose, glycosylated hemoglobin with significant decrease in insulin and total hemoglobin. The activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and the levels of reduced glutathione were decreased while increases in the levels of lipid peroxidation markers were observed in aortic tissues of diabetic rats. Oral administration of diosgenin to diabetic rats significantly decreased the plasma glucose and increased the insulin level based on a dose dependent manner. Diosgenin at a dose of 40 mg/kg b.w. was more pronounced effect than the other two doses and used for further studies. All the manifestations observed in diabetic rats were significantly reversed to near normal at a dose of 40 mg/kg b.w. of diosgenin. These findings suggest that diosgenin could have a beneficial role against aortic damage induced by oxidative stress in diabetic state, which was evidenced by the propensity of diosgenin to modulate the antioxidant defense and to decrease the lipid peroxidation in aorta.

Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats.

The present study was to evaluate the hepatoprotective effect of hesperetin (HTN) on cadmium (Cd) induced hepatotoxicity in male Wistar rats. Administration of Cd (3 mg/kg body weight/day) subcutaneously for 21 days, the levels of hepatic markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and bilirubin were significantly increased in serum. The levels oxidative stress markers, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), conjugated dienes (CD) and protein carbonyl content (PCC) were also significantly increased while the levels of vitamin C, vitamin E, reduced glutathione (GSH), total sulphydryl group (TSH) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) were significantly decreased in the liver of Cd intoxicated rats. HTN, a flavanone in citrus fruits, administrated orally along with Cd injection for 21 days, significantly revert back the status of serum hepatic markers, oxidative stress markers and antioxidant markers in the liver tissue to near normal level in a dose dependent manner. HTN at a dose of 40 mg/kg body weight/day exhibits significant (p<0.05) hepatoprotection compared with other two doses (10 and 20 mg/kg body weight/day). The histopathological studies in the liver of rats also supported that HTN (40 mg/kg) markedly reduced the toxicity of Cd and preserved the histoarchitecture of the liver tissue to near normal. Thus, the results suggest that HTN acts as a potent hepatoprotective agent against Cd induced hepatotoxicity in rats.

Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats.

Oxidative stress has been suggested as a contributory factor in development and complication of diabetes. The aim of the study was to evaluate the effect of diosmin (DS) in oxidative stress in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats by measuring the lipid peroxidation (LPO) as well as the ameliorative properties. Experimental diabetes was induced by a single intraperitoneal (i.p) injection of STZ (45 mg/kg body weight (b.w.)) dissolved in 0.1 mol/L citrate buffer (pH 4.5), 15 min after the i.p administration of NA (110 mg/kg b.w.). Diabetic rats exhibited increased plasma glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of low-molecular weight antioxidants vitamin C, vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of LPO markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with DS (100mg/kg/day) for a period of 45 days showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. These results indicated that DS has potential ameliorative effects in addition to its antidiabetic effect in type 2 diabetic rats.