Arsenic-Induced Hepatic Toxicity and Its Attenuation by Fruit Extract of Emblica officinalis (Amla) in Mice

Arsenic a metalloid and environmental contaminated has been found to be associated with public health problems in the affected areas. It is naturally occurred in groundwater and its accumulation in plant and animals leads to toxicity in several tissues most notably hepatic organ. Arsenic exposures (3 mg/kg body weight/day for 30 days) in mice exhibited increased arsenic and Zn levels in hepatocytes associated with enhanced oxidative stress in hepatocytes while there were no significantly changes were observed in Cu level. An increase in the lipid peroxidation and decrease in the levels of reduced glutathione and activity of superoxide dismutase, catalase, and glutathione peroxidase were observed in arsenic treated mice as compared to controls. Arsenic exposure in mice also caused a significant change in serum biomarkers in the SGOT, SGPT and creatinine as compared to the controls. There were no significant changes in the serum levels of total protein in these mice. Co-administration of arsenic and fruit extract of amla (500 mg/kg body weight/day for 30 days) caused a significant reduction of arsenic transference associated with significantly decreases hepatic arsenic levels and balanced the antioxidant enzyme and levels of serum hepatic enzymes like SGOT and SGPT. The results of the present study clearly demonstrate the antioxidant property of amla that could be responsible for its protective efficacy in arsenic induced hepatic toxicity.     

Protective Effect of Calendula officinalis L. Flowers Against Monosodium Glutamate Induced Oxidative Stress and Excitotoxic Brain Damage in Rats

Monosodium glutamate (MSG) is a popular flavour enhancer used in food industries; however, excess MSG is neurotoxic. Oxidative stress is well documented in MSG induced neurotoxicity. The compounds having antioxidant and anti-inflammatory properties reportedly possess beneficial effects against various neurotoxic insults. Calendula officinalis Linn. flower extract (COE) is known for its potent antioxidant and anti-inflammatory activities. Hence, this present study has been designed to evaluate the neuroprotective effect of COE on MSG-induced neurotoxicity in rats. Adult Wistar rats were administered systemically for 7 days with MSG and after one h of MSG injection, rats were treated with COE (100 and 200 mg/kg) orally. At the end the treatment period, animals were assessed for locomotor activity and were sacrificed; brains were isolated for estimation of LPO, GSH, CAT, TT, GST, Nitrite and histopathological studies. MSG caused a significant alteration in animal behavior, oxidative defense (raised levels of LPO, nitrite concentration, depletion of antioxidant levels) and hippocampal neuronal histology. Treatment with COE significantly attenuated behavioral alterations, oxidative stress, and hippocampal damage in MSG-treated animals. Hence, this study demonstrates that COE protects against MSG-induced neurotoxicity in rats. The antioxidant and anti-inflammatory properties of COE may be responsible for its observed neuroprotective action.     

Alleviation of Dimethylnitrosamine-Induced Liver Injury and Fibrosis by Supplementation of Anabasis articulata Extract in Rats

Anabasis articulata (Forssk) Moq. (Chenopodiaceae) is an herb, grows in Egypt, and used in folk medicine to treat diabetes, fever, and kidney infections. The protective and therapeutic effects of the ethanol extract of A. articulata aerial parts were evaluated against dimethylnitrosamine (DMN)-induced liver fibrosis, compared with the standard drug, silymarin. Hepatic hydroxyproline content, serum transforming growth factor-β1 (TGF-β1), interleukin 10 (IL-10) and fructosamine were measured as liver fibrosis markers. Hepatic malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), glutathione reductase (GR) and glutathione content (GSH) were measured as oxidant/antioxidant markers. Parallel histopathological investigations were also performed. Protective and therapeutic administration of A. articulata (100 mg/kg daily for 4 weeks), markedly prevented DMN-induced loss in body and liver weights. The extract significantly inhibited the elevation of hepatic hydroxyproline, NO and MDA (P < 0.05), as well as serum fructosamine, and TGF-β1 (P < 0.05) induced by DMN while it restored IL-10 to normal level in both protective and therapeutic groups. Furthermore, A. articulata prevented the depletion in CAT, GR, and GSH levels (P ≤ 0.05). In addition, oral administration of A. articulata extract and silymarin to both protective and therapeutic groups reduced the increase in liver function enzyme activities; alanine and aspartate amintransferases, gamma-glutamyl transferase in addition to alkaline phosphatase, and caused significant increase in serum albumin concentration as compared to DMN group. These data corresponded closely with those obtained for the drug silymarin. Histopathological studies confirmed the biochemical data and revealed remarkable improvement in liver architecture. Thus, it could be concluded that, A. articulata extract exhibited in vivo hepatoprotective and therapeutic effects against DMN-induced liver injury and may act as a useful agent in controlling the progression of hepatic fibrosis through reduction of oxidative stress and improving liver function.     

Effect of Certain Antibiotics Against Filarial Parasite <Emphasis Type="Italic">Brugia malayi</Emphasis> In Vitro: Possible Role of Oxidative Stress

WHO-Tropical Disease Research scheme highlighted the need for development of new anti-filarial drugs. Certain antibiotics have recently been found effective against Wolbachia, co-existing symbiotically with filarial parasites. Inflammatory response entails oxidative mechanism to educe direct anti-microbial effect. In the present study microfilariae were maintained in vitro in medium supplemented with varying concentrations of tetracycline, doxycycline (20–100 μg/ml) or ciprofloxacin (50–250 μg/ml) separately to find out any involvement of oxidative mechanism in the anti-filarial effect of these antibiotics. Loss of motility of the microfilariae was measured after 48 h and correlated with the levels of MDA, nitric oxide and protein-carbonylation. Significant loss of microfilarial motility was recorded with increasing concentration of tetracycline and doxycycline but with ciprofloxacin the effect was not marked. Agents with high antifilarial activity revealed significant association with oxidative parameters in a dose dependent manner. The result suggests that oxidative effect might be exploited to design novel antifilarial drug candidate.     

Free Radical Scavenging Properties of Skin and Pulp Extracts of Different Grape Cultivars In Vitro and Attenuation of H2O2-Induced Oxidative Stress in Liver Tissue Ex Vivo

Grapes are the richest source of antioxidants due to the presence of potent bioactive phytochemicals. In this study, the phytochemical contents, scavenging activities and protective role against H₂O₂-induced oxidative stress in liver tissue ex vivo of four grape (Vitis vinifera) cultivars extracts, namely Flame seedless (black), Kishmish chorni (black with reddish brown), Red globe (red) and Thompson seedless mutant (green), were evaluated. The total phenolics and flavonoids content in pulp or skin fractions of different grape cultivars were in the range of 47.6–310 mg gallic acid equivalent/g fresh weight (fw), and 46.6–733.3 µg catechin equivalent/g fw respectively. The scavenging activities in skin of different grape varieties against 2,2-diphenyl-1-picrylhydrazyl (44–58 %), hydrogen peroxide (15.3–18.6 %), and hydroxyl radicals (50–85 %), were higher than pulp of the corresponding cultivars. These scavenging activities of grape extracts were found to be significantly (p < 0.01) correlated with the levels of total phenols, flavonoids and ascorbic acid. Liver tissues from goat treated with H₂O₂ (500 μM) showed significantly decreased GSH content by 42.9 % and activities of catalase by 50 % and glutathione reductase by 66.6 %; while increased thiobarbituric acid reactive substances and nitric oxide level by 2.53- and 0.86-fold, respectively, and activity of glutathione S-transferase by 0.96-fold. Grape skin extracts showed the stronger protective activity against H₂O₂-induced oxidative stress in liver tissue ex vivo, than its pulp of any cultivar; and the Flame seedless (black) cultivar showed the highest potential. In conclusion, our study suggested that the higher antioxidant potential, phytochemical contents and significant scavenging capacities in pulp and skin of grape extracts showed the protective action of grape extracts against H₂O₂-induced oxidative stress in liver tissue ex vivo.     

Protective Role of <Emphasis Type="SmallCaps">l</Emphasis>-Arginine Against Free-Radical Mediated Oxidative Damage in Patients with Unstable Angina

Unstable angina is a critical condition of heart resulting from narrowing of vessels supplying blood to heart. Ischemia of the myocardium leads to oxidative stress and severe tissue damage. The objective of the present study was to determine the effect of l-arginine administration on the oxidant–antioxidant homeostasis which otherwise gets imbalanced in patients with cardiovascular diseases. The results obtained, show improvement in the oxidant–antioxidant levels of the subjects upon incorporation of l-arginine. Our findings suggest that supplementation of l-arginine along with regular anti-anginal therapy may be beneficial to the patients of unstable angina.     

Antioxidant Activities of Hydroalcoholic Extract of <Emphasis Type="Italic">Ocimum sanctum</Emphasis> Against Cadmium Induced Toxicity in Rats

The present study was undertaken to analyze the antioxidant (both enzymic and nonenzymic) activities of leaves of Ocimum sanctum hydroalcoholic extract against cadmium induced damage in albino rats. Oral administration of cadmium as CdCl₂ (6.0 mg/kg body weight) led to significant elevation of lipid peroxidation (LPO) levels and significantly decreased Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx), Reduced Glutathione (GSH) and Vitamin C (Ascorbate) levels. Administration of Ocimum sanctum extract (100 mg/kg body weight, po) and (200 mg/kg body weight, po) before and after cadmium intoxication showed a significant decrease in LPO levels and significant increase in SOD, CAT, GPx, GSH and Ascorbate levels. The results suggest that oral administration of Ocimum sanctum extract provides significant protection against cadmium induced toxicity in Wistar albino rats.     

Antidyslipidemic Effect of Ocimum sanctum Leaf Extract in Streptozotocin Induced Diabetic Rats

The antidyslipidemic activity of Ocimum sanctum leaf extract was studied in streptozotocin induced diabetic rats. In this model, there was significant increase in plasma markers of diabetic-dyslipidemia following diminution of lipid metabolizing enzymes. Oral administration of leaf extract (500 mg/kg b.w.p.o.) for 15 days resulted in significant decrease in diabetogenic and dyslipidemia parameters; namely blood glucose, glycosylated hemoglobin, lipid peroxide, free fatty acids, small dense low density lipoprotein, lipid and protein components of plasma lipoproteins, adipose and liver. The regulation of lipids was accompanied by stimulation of postheparin lipolytic activity, reactivation of lecithin cholesterol acyl transferase and hepatic lipoprotein lipase enzymes. The results of the present study demonstrated antidyslipidemic and antioxidant activities in leaf extract of O. sanctum which could be used in prevention of diabetic-dyslipidemia and related complications.     

Evaluation of Low Blood Lead Levels and Its Association with Oxidative Stress in Pregnant Anemic Women: A Comparative Prospective Study

To correlate blood lead levels (BLLs) and oxidative stress parameters in pregnant anemic women. A total of 175 pregnant women were found suitable and included for this study. Following WHO criteria, 50 each were identified as non-anemic, mild anemic and moderate anemic and 25 were severe anemic. The age of all study subjects ranged from 24–41 years. At admission, BLLs and oxidative stress parameters were estimated as per standard protocols and subjected with ANOVA, Pearson correlation analysis and cluster analysis. Results showed significantly (p < 0.01) high BLLs, zinc protoporphyrin (ZPP), oxidized glutathione (GSSG), lipid peroxide (LPO) levels while low delta aminolevulinic acid dehydratase (δ-ALAD), iron (Fe), selenium (Se), zinc (Zn), haemoglobin (Hb), haematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), red blood cell (RBC) count, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (TAC) in all groups of anemic pregnant women as compared with non anemic pregnant women. In all groups of pregnant women, BLLs showed significant (p < 0.01) and direct association with ZPP, GSSG and LPO while inverse relation with δ-ALAD, Fe, Se, Zn, Hb, Hct, MCV, MCH, MCHC, RBC, GSH, SOD, CAT and TAC. Study concluded that low BLLs perturb oxidant-antioxidant balance and negatively affected hematological parameters which may eventually Pb to Fe deficiency anemia during pregnancy.     

Evaluation of Antioxidants in the Kidney of Streptozotocin Induced Diabetic Rats

Diabetes mellitus is one of the most common endocrine metabolic disorders. Dual endocrine deficits of impaired insulin action (insulin resistance) and inadequate insulin secretion create an environment of chronic hyperglycemia and general metabolic disarray. Oxidative stress plays an important role in diabetic pathogenesis. Oxidative stress induced by streptozotocin (STZ) has been shown to damage pancreatic beta cell and produce hyperglycemia in rats. The present study was made to evaluate the antioxidant activity of ethanolic extract of the Evolvulus alsinoides in STZ induced rats. The antioxidant activities were done by using standard protocols. For histopathological analysis, the pancreatic tissues of all experimental groups were fixed with 10 % formalin for 24 h then the samples were stained with hematoxylin–eosin for the microscopic observation. Our results showed the significant decrease in lipid peroxidation and increases in the antioxidant (both enzymatic and nonenzymatic) levels after treatment with standard as well as the E. alsinoides. There is no significant difference between control and plant alone group rats. The histopathology reports also revealed non-toxic effect and protective effect of E. alsinoides in the kidney of STZ induced diabetic rats. Our result indicated that the E. alsinoides extract effectively increased the antioxidant level thereby it prevents oxidative stress during diabetes mellitus and also it showed the protective effect on kidney of STZ induced rats. Hence it can be used to maintain the antioxidant level during diabetes mellitus.     

Anti-Oxidative Effect of <Emphasis Type="Italic">Cassia auriculata</Emphasis> on Streptozotocin Induced Diabetic Rats

The anti oxidative effect of administration of 100 mg/kg bw and 200 mg/kg bw of the flower powder of Cassia auriculata (CFP) for 45 days to normoglycemic and diabetic rats (streptozotocin induced) was studied. Anti oxidative effect was not observed in normoglycemic rats in the experiment. There was significant (P > 0.05) increase in the level of Thio Barbituric Acid Reactive Substances (TBARS), hydroperoxide and conjugated dienes and significant (P > 0.05) decrease in the catalase, superoxide dismutase and glutathione peroxidase activities and in the level of ascorbic acid, vitamin E and reduced glutathione in diabetic rats. The flower powder of Cassia auriculata significantly (P > 0.05) decreased the TBARS, hydroperoxide and conjugated dienes and increased the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and non enzymic anti oxidants (ascorbic acid, vitamin E and reduced glutathione). The antioxidatve effect of 200 mg/kg bw CFP was significantly (P > 0.05) better than 100 mg/kg bw CFP and the reference drugs (tolbutamide and metformin). The mode of action of CFP remains to be elicited.     

Hypolipidemic Activity of Cassia tora Seeds in Hyperlipidemic Rats

The hypolipidemic activity of Cassia tora (Chakvat, Chakunda) (Family: Caesalpiniaceae) seeds extract have been studied in two models of hyperlipidemia in rats. In an acute model, hyperlipidemia was induced by injecting a single dose of Triton WR-1339 (400 mg/kg, b.w.) intraperitonially in rats. Feeding with C. tora seed extract at the dose of 500 mg/kg, b.w. exerted significant lipid lowering effect as assessed by the reversal of plasma levels of total cholesterol, phospholipids, triglyceride and reactivation of post heparin lipolytic activity. In the chronic model, hyperlipidemia was induced by feeding with cholesterol rich-HFD in rats. The treatment with seeds extract of C. tora (500 mg/kg, b.w.) simultaneously for 15 days also caused lowering of lipid levels in plasma and liver following reactivation of plasma post heparin lipolytic activity and hepatic lipoprotein lipase activity in animals. The hypolipidemic activity of C. tora seeds was compared with a standard drug guggulipid (200 mg/kg, b.w.) in both models.     

Hypolipidemic Effect of <Emphasis Type="Italic">Celastrus paniculatus</Emphasis> in Experimentally Induced Hypercholesterolemic Wistar Rats

The objective of the present study was to evaluate hypolipidemic effect of methanolic extract of Celastrus paniculatus in experimentally induced hypercholesterolemic rats. Hypercholesterolemia was induced by feeding the animals with high fat diet. Oral administration of methanolic seed extract (50%) of Celastrus paniculatus at the optimized dose of 65 mg/kg body weight, substantially reduced the plasma total cholesterol, triglycerides and LDL cholesterol in comparison with induced hypercholesterolemic animal group and the results were comparable with the standard hypocholesterolemic drug and almost similar to the control group. Atherogenic index and liver weight of treated animals also showed significant decrease compared to the hypercholesterolemic animals. It substantially increased the HDL cholesterol level as compared to control group. A significant increase in the activities of lipoprotein lipase and plasma LCAT enhanced hepatic bile acid synthesis and thereby, increased degradation of cholesterol to neutral sterols. Furthermore, the activities of HMG-CoA reductase, glucose 6-phosphate dehydrogenase and malate dehydrogenase were significantly reduced. Histological studies showed less cholesterol deposits in the aorta of animals fed with seed extract of C. paniculatus compared to the induced hypercholesterolemic animals not given C. paniculatus supplement.     

Effect of Turmeric and its Active Principle Curcumin on T<Subscript>3</Subscript>-Induced Oxidative Stress and Hyperplasia in Rat Kidney: A Comparison

The present study was designed to compare the potential of turmeric and its active principle curcumin on T₃-induced oxidative stress and hyperplasia. Adult male Wistar strain rats were rendered hyperthyroid by T₃ treatment (10 μg · 100 g⁻¹ · day⁻¹ intraperitoneal for 15 days in 0.1 mM NaOH) to induce renal hyperplasia. Another two groups were treated similarly with T₃ along with either turmeric or curcumin (30 mg kg⁻¹ body weight day⁻¹ orally for 15 days). The results indicate that T₃ induces both hypertrophy and hyperplasia in rat kidney as evidenced by increase in cell number per unit area, increased protein content, tubular dilation and interstitial edema. These changes were accompanied by increased mitochondrial lipid peroxidation and superoxide dismutase activity without any change in catalase activity and glutathione content suggesting an oxidative predominance. Both turmeric and curcumin were able to restore the level of mitochondrial lipid peroxidation and superoxide dismutase activity in the present dose schedule. T₃-induced histo-pathological changes were restored with turmeric treatment whereas curcumin administration caused hypoplasia. This may be due to lower concentration of curcumin in the whole turmeric. Thus it is hypothesized that regulation of cell cycle in rat kidney by T₃ is via reactive oxygen species and curcumin reveres the changes by scavenging them. Although the response trends are comparable for both turmeric and curcumin, the magnitude of alteration is more in the later. Turmeric in the current dose schedule is a safer bet than curcumin in normalizing the T₃-induced hyperplasia may be due to the lower concentration of the active principle in the whole spice.     

Antidyslipidemic and Antioxidant Activities of Hibiscus rosa sinensis Root Extract in Alloxan Induced Diabetic Rats

The antidyslipidemic activity of Hibiscus rosa sinensis (Malvaceae) root extract has been studied in alloxan induced diabetic rats. In this model, oral administration of root extract (500 mg/kg bw. p.o.) for 15 days resulted in significant decreased in the levels of blood glucose, plasma lipids and reactivated post heparin lipoprotein lipase activity in alloxan induced diabetic rats. Furthermore, the root extract (50–500 μg) when tested for its antioxidant activity, inhibited the generation of super oxide anions and hydroxyl radicals, in both enzymic and non enzymic systems in vitro. The results of the present study demonstrated antidyslipidemic and antioxidant activities in root extract of H. rosa sinensis which could be used in prevention of diabetic-dyslipidemia and related complications.     

Immuno-Modulatory Effect and Therapeutic Potential of <Emphasis Type="Italic">Brugia malayi</Emphasis> Cystatin in Experimentally Induced Arthritis

Helminths are known to modulate host’s immune system and understanding this modulation can help in identification of novel therapeutic agents for autoimmune diseases. In this study, we have assessed the immune-modulatory activity and the therapeutic effect of Brugia malayi recombinant cystatin (rBmCys) in methylated BSA (mBSA) induced arthritis using rodent model. Administration of rBmCys has suppressed the severity of mBSA-arthritis in mastomys by reducing paw swelling and other clinical disease parameters as evident from significantly decreased arthritic index. The anti-arthritic effect of rBmCys was also confirmed by decreased histopathological score for synovitis, bone erosion and fibrosis in the tissue sections of paws. Further, this therapeutic effect of cystatin was found to be associated with significantly decreased production of IFN-γ and TNF-α and increased release of IL-4 and IL-10 cytokines. These results implied that rBmCys treatment has alleviated mBSA-induced arthritis and thus can be a promising alternative agent for the treatment of arthritis.