Elevated Thiobarbituric Acid Reactive Substances Research Articles

Effect of Acetyl-L-Carnitine on Antioxidant Status, Lipid Peroxidation, and Oxidative Damage of Arsenic in Rat.

Arsenic (As) is a widespread environmental contaminant present around the world in both organic and inorganic forms. Oxidative stress is postulated as the main mechanism for As-induced toxicity. This study was planned to examine the protective effect of acetyl-L-carnitine (ALC) on As-induced oxidative damage in male rats. Animals were randomly divided into four groups of control (saline), sodium arsenite (NaAsO2, 20 mg/kg), ALC (300 mg/kg), and NaAsO2 plus ALC. Animals were dosed orally for 28 successive days. Blood and tissue samples including kidney, brain, liver, heart, and lung were collected on the 28th day and evaluated for oxidative damage and histological changes. NaAsO2 exposure caused a significant lipid peroxidation as evidenced by elevation in thiobarbituric acid-reactive substances (TBARS). The activity of antioxidant enzymes such as glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), as well as sulfhydryl group content (SH group) was significantly suppressed in various organs following NaAsO2 treatment (P < 0.05). Furthermore, NaAsO2 administration increased serum values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and bilirubin. Our findings revealed that co-administration of ALC and NaAsO2 significantly suppressed the oxidative damage induced by NaAsO2. Tissue histological studies have confirmed the biochemical findings and provided evidence for the beneficial role of ALC. The results concluded that ALC attenuated NaAsO2-induced toxicity, and this protective effect may result from the ability of ALC in maintaining oxidant-antioxidant balance.

Neuroprotective effect of Tagara, an Ayurvedic drug against methyl mercury induced oxidative stress using rat brain mitochondrial fractions.

BackgroundMethyl mercury (MeHg), an important environmental toxicant is implicated in neurological disorders such as Hunter-Russell syndrome and Autism. Therefore, the present work is in search of new drugs that can alleviate MeHg toxicity. In this connection, Tagara, an ayurvedic drug is used for assessing its neuro protective effect against MeHg toxicity.MethodsIn the present study, we assessed the phytochemical contents of Tagara by colorimetric and HPLC analyses. The neuroprotective effect of Tagara on MeHg induced neurotoxicity was measured in terms of viability by MTT assay and oxidative stress in terms of catalase activity, glutathione and thiobarbituric acid reactive substance levels. Further, the chelating effect of Tagara towards MeHg was performed to identify the molecular mechanism. Statistical analysis was done by statistical package for social sciences (SPSS) version 16.0.ResultsThe results demonstrated that Tagara contains significant amounts of phenols and flavonoids. Also, HPLC analysis of Tagara revealed the presence of essential oils such as hydroxyvalerenic and valerenic acids. Our results demonstrated that exposure of rat brain mitochondrial fractions to MeHg resulted in a dose dependent death in MTT assay and IC50 value was found to be 10 μM. However, a 250 μg dose of Tagara effectively prevented MeHg induced mitochondrial damage. The oxidative stress caused by MeHg results in elevated levels of reactive oxygen species as evidenced by elevated TBARS (Thiobarbituric acid-reactive substances) levels and diminished catalase enzyme activity and glutathione content. However, Tagara at 250 μg concentration offsets these alterations caused by MeHg. Further, Tagara also diminished GSH oxidation caused by MeHg, confirming its chelating effect, one of the molecular mechanisms that triggers protection against oxidative damage.ConclusionOur results revealed that MeHg induced toxicity is predominantly mediated through oxidative stress mechanism and the propensity of Tagara to abolish such reactions. Hence, we propose that Tagara with a source of potential neuroprotectants may be a useful approach to alleviate MeHg associated neurotoxicity.

Neuroprotective effects of Bacopa monniera whole-plant extract against aluminum-induced hippocampus damage in rats: evidence from electron microscopic images.

Impaired antioxidant system and structural changes in hippocampus are considered as key instigators of neurodegenerative diseases. The present study aimed to investigate the antioxidant and tissue protective properties of Bacopa monniera whole-plant extract (BME) against aluminum (Al)- induced oxidative stress and hippocampus damage in rats. Male Wistar rats were evenly divided into four groups, nine in each and labeled as control, Al treated (10 mg/kg), BME administered (40 mg/kg) and combination of both Al plus BME (Al+BME) treated groups. After one month of treatment by oral administration, antioxidant status was determined, and structural changes in the hippocampus were evaluated by electron microscopy. Al-induced increased oxidative damage in the hippocampus was revealed by elevated thiobarbituric acid reactive substances (TBARS). This increased lipid peroxidation was associated with significantly decreased antioxidant enzyme activities, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). However, aluminum intoxicated rats treated with BME for 30 days showed significantly restored antioxidant enzyme activities along with decreased TBARS (P < 0.01). Further evidences from electron micrographs clearly indicated that Al-induced vacuolation, lipofuscin deposition and pyramidal cell degeneration in the hippocampus was attenuated with co-administration of the whole-plant extract. Our results demonstrate that structural derangement in hippocampus by aluminum is directly proportionate with increased lipid peroxidation. Nevertheless, B. monniera treatment potentiates the antioxidant status and suppressed the tissue damage induced by Al-intoxication. These findings suggest that B. monniera whole-plant extracts can be considered as a possible remedy to counteract aluminum-associated neurological disorders.

Hepatotoxicity and genotoxicity of patulin in mice, and its modulation by green tea polyphenols administration

Patulin (PAT) is a mycotoxin produced by certain species of Penicillium, Aspergillus, and Byssochlamys. Previous studies demonstrated its cytotoxic, genotoxic, and mutagenic effects in different cell lines. However, there is little information available concerning its toxic behavior in vivo. In the present study, we investigated PAT-induced hepatotoxicity and genotoxicity in mice. We also investigated the antioxidant and anti-genotoxicity efficiency of green tea polyphenols (GTP) against PAT-induced toxicity. We found that PAT-treatment induced serum alanine transaminase (ALT) and aspartate transaminase (AST) activities significantly. PAT-induced lipid peroxidation was confirmed with the elevation of thiobarbituric acid-reactive substances (TBARS). Moreover, the increasing of reactive oxygen species (ROS) and decreasing of GSH level implied its oxidative damage mechanism. In bone marrow cell, PAT was found to induce micronucleus and chromosomal aberration formation. In addition, our result suggested that GTP administration has dose-dependent antioxidative and antigenotoxic effect in against PAT-induced hepatotoxicity and genotoxicity.

The protective effect of Phoenix dactylifera L. seeds against CCl4-induced hepatotoxicity in rats

Ethnopharmacological relevanceIn traditional Egyptian medicine, Phoenix dactylifera L. (date palm) seeds are listed in folk remedies for the management of diabetes, liver diseases and gastrointestinal disorders. The present study was conducted to investigate the protective effect of Phoenix dactylifera L. seeds aqueous suspension against the chemically-induced hepatic injury in rats. MethodsLiver injury was achieved by exposing Wistar rats to CCl4 (10% in olive oil; 0.5mL/rat; IP) twice a week for 4 weeks. Along with CCl4, aqueous suspensions of raw or roasted Phoenix dactylifera seeds (1.0g/kg) were administered orally in a daily manner. ResultsOur results demonstrated that Phoenix dactylifera seeds significantly improved the CCl4-induced alterations in liver function parameters (AST, ALT, ALP and albumin). Moreover, the CCl4-induced oxidative stress, represented by elevated thiobarbituric acid reactive substance (TBARS), nitric oxide and oxidative DNA damage, was ameliorated by Phoenix dactylifera seeds treatment. In addition, Phoenix dactylifera seeds restored the activities of hepatic antioxidant enzymes (superoxide dismutase and glutathione S-transferase) that were declined after CCl4 treatment. Examination of liver histopathology revealed that Phoenix dactylifera seeds attenuate the incidence of liver lesions (including vacuolization and fibroblast proliferation) triggered by CCl4 intoxication. ConclusionThe Phoenix dactylifera seeds could be a promising candidate for protection against the CCl4-induced liver intoxication, and this hepatoprotective effect might be attributed to the antioxidant and free radical scavenging activities.

Ethanol Plus the Jo2 Fas Agonistic Antibody‐Induced Liver Injury is Attenuated in Mice with Partial Ablation of Argininosuccinate Synthase

Argininosuccinate synthase (ASS) is an enzyme shared by the urea cycle and the l-citrulline/nitric oxide (NO·) cycle. ASS is the rate-limiting enzyme in the urea cycle and along with nitric oxide synthase 2 (NOS2), it endows cells with the l-citrulline/NO· salvage pathway to continuously supply l-arginine from l-citrulline for sustained NO· generation. Thus, ASS conditions NO· synthesis by NOS2. Because of the relevance of NOS2 activation for liver injury, we examined the contribution of ASS to NO· generation and how it impacts liver injury. Wild-type (WT) mice and Ass(+/-) mice (Ass(-/-) mice are lethal) were intraperitoneally injected with ethanol (EtOH) at a dose of 2.5g/kg of body weight twice a day for 3days. Two hours after the last dose of EtOH, mice were administered the agonistic Jo2 anti-mouse Fas monoclonal antibody (Ab) at a dose of 0.2μg/g of body weight. Mice were sacrificed 8hours after the Jo2 Ab injection. Markers of nitrosative and oxidative stress as well as liver damage were analyzed. EtOH plus Jo2 injection induced liver injury as shown by serum alanine aminotransferase and aspartate aminotransferase activity, liver pathology, TUNEL, and cleaved caspase-3 were lower in Ass(+/-) mice compared with WT mice, suggesting that ASS contributes to EtOH plus Jo2-mediated liver injury. CYP2E1 induction, glutathione depletion, and elevated thiobarbituric acid reactive substances were comparable in both groups of mice, suggesting that CYP2E1-mediated oxidative stress is not linked to ASS-induced liver injury. In contrast, NOS2 induction, 3-nitrotyrosine adducts formation and elevated nitrites, nitrates, and S-nitrosothiols were higher in livers from WT mice than from Ass(+/-) mice. Decreased nitrosative stress causes lower EtOH plus Jo2-induced liver injury in Ass(+/-) mice.

Hepatoprotective effect of peptic hydrolysate from salmon pectoral fin protein byproducts on ethanol-induced oxidative stress in Sprague–Dawley rats

Bioactive peptides were generated by pepsin hydrolysis from salmon pectoral fin protein byproduct, and the hepatoprotective effect of the peptic hydrolysate (PH) on ethanol-induced oxidative stress was investigated in Sprague–Dawley rats. Administration of ethanol for 4weeks significantly (p<0.05) increased serum markers of liver damage, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase; however, these activities decreased significantly (p<0.05) after PH administration. Elevated thiobarbituric acid reactive substance levels in liver tissue and serum decreased significantly (p<0.05) following administration of PH. Ethanol exposure significantly (p<0.05) decreased glutathione contents in liver and serum, and hepatic antioxidant enzyme activities such as superoxide dismutase and glutathione peroxidase, while the PH treatment significantly (p<0.05) increased these altered parameters. These results indicate that the PH had a protective effect against ethanol-induced hepatotoxicity that was comparable to that of silymarin, which was supported by evaluating liver histopathology in the rats.

Curcumin Protects Metronidazole and X-ray Induced Cytotoxicity and Oxidative Stress in Male Germ Cells in Mice

Metronidazole (MTZ) is a common antiparasitic and antibacterial drug. The drug and X-ray induced effects in mouse sperm count, sperm head abnormality and some oxidative stress parameters have been studied. Simultaneously the protective role of curcumin has been evaluated. MTZ, 40 mg/kg bw and 13.4 mg/kg bw × 3 days exposure induced abnormal sperm head and reduced total sperm count in Swiss albino mice both after 24 h and 35 days of exposure. However, MTZ treatment in mice receiving X-ray irradiation (0.5 Gy) did not changed the incidence of abnormal sperm population or decrease in the total sperm count. Hepatic glutathione (GSH), superoxide dismutase (SOD) declined significantly during the treatment phase with significant rise in lipid peroxidation of the tissue. The cellular changes were estimated by using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS). Elevated TBARS is indicative of oxidative stress in treated mice. Furthermore, curcumin pre-treatment apparently reduced the frequency of sperm head abnormality and TBARS induced by MTZ alone or in combination with X-ray and increased the levels of hepatic GSH and SOD. The additive effects of MTZ and X-ray could not be observed with regards to sperm head abnormality and total sperm count in the tested dose range although the cellular antioxidants were found to be significantly lowered and lipid peroxidantion increased. The possible role of MTZ and X-ray inducing sperm abnormality, decreased sperm count and alteration in GSH, SOD and TBARS and defensive role of curcumin have been evaluated.

Antihyperglycemic and antioxidative effect of hydro - methanolic (2:3) extract of the seed of Swietenia mahagoni (L.) Jacq. in streptozotocin-induced diabetic male albino rat: An approach through pancreas

The goal of this study was to investigate the effects of the hydro - methanolic (2:3) extract of the seed of Swietenia mahagoni (L.) Jacq. for the management of streptozotocin (STZ)-induced diabetes. Wistar rats were divided equally into four groups (n = 6): normal control, diabetes control, diabetes + extract treated, and diabetes + metformin treated. The extract (25 mg/100 g by weight) and metformin (2.5 mg/100 g by weight) were administered once a day, orally by gavages for 21 days at fasting condition. Hexokinase, glucose-6-phosphate dehydrogenase, and glucose-6-phosphatase activities were measured in hepatic tissue. Activities of catalase (CAT), peroxidase (Px), and superoxide dismutase (SOD), along with the quantity of thiobarbituric acid reactive substances (TBARS) and conjugated diene (CD) in hepatic and renal tissues, were assessed. Histoarchitecture of the pancreas and serum insulin level were also evaluated. Significant diminution in the activities of hepatic hexokinase and glucose-6-phosphate dehydrogenase along with elevation in glucose-6-phosphatase were noted in STZ-induced animals with diabetes in respect to control animals. Level of fasting blood glucose (FBG) was elevated in animals with diabetes. Activities of CAT, Px, and SOD were diminished significantly along with the elevation in TBARS and CD levels in animals with diabetes. Diameter of pancreatic islets, count of islets, and degeneration in pancreatic acini were also noted in animals with diabetes. Treatment of these animals with extract or metformin resulted in substantial recovery in the aforementioned biosensors toward the control level. This recovery is not equal to metformin because the plant extract is not the pure form of effective ingredient(s) but provides insight to the pharmaceutical industries that the extract has a protective therapeutic effect against diabetes through ß-cell regeneration capacity.

Evaluation of venlafaxine on glucose homeostasis and oxidative stress in diabetic mice

Depression occurs frequently with diabetes affecting the quality of life. All major classes of antidepressants have been shown to have a direct pharmacologic effect on metabolic function, which further worsens glycemic control. There were no reports on the effects of venlafaxine on glucose levels and oxidative stress in diabetic animals. The present study evaluated the effects of venlafaxine (8 and 16 mg/kg per d) on glucose homeostasis along with oxidative stress in brain in diabetic mice (streptozotocin (STZ), 40 mg/kg per d for 5 days). We observed that 21 days of administration of venlafaxine (8 and 16 mg/kg per d) in diabetic mice significantly enhanced swimming in normal and STZ-treated mice with a corresponding reduction in immobility. No significant difference in blood glucose levels was observed in diabetic and normal mice following venlafaxine treatment. Venlafaxine (16 mg/kg) reversed STZ-induced elevated thiobarbituric acid reactive substance (TBARS) levels and also restored the glutathione (GSH) levels in diabetic mice. Venlafaxine (8 and 16 mg/kg) per se does not produce any significant effect in normal animals. The results indicate a dose-dependent antidepressant action of venlafaxine in diabetes-induced depressive mice. Furthermore, the blood glucose levels were not significantly altered in normal and diabetic mice. In addition, venlafaxine exhibited a decrease in TBARS and elevation in GSH levels in mice brain. Venlafaxine drug treatment appears to be safer for depression associated with diabetes.

Nitric oxide synthase inhibition abrogates hydrogen sulfide-induced cardioprotection in mice

The cardioprotective property of hydrogen sulfide (H(2)S) is recently reported. However, cellular signaling cascades mediated by H(2)S are largely unclear. This study was undertaken to explore the molecular mechanism of H(2)S-induced cardioprotection in mouse heart by utilizing in vivo model of cardiac injury. We report here that intraperitoneal administration of sodium hydrogen sulfide (NaHS, 50 μmol kg(-1 )day(-1) for 2 days), a H(2)S donor, significantly (P ≤ 0.05) increased nitric oxide levels in serum as well as myocardium without any sign of myocardial injury. Typical characteristics of myocardial injury induced by isoproterenol (ISO) administration was significantly (P ≤ 0.05) abrogated by NaHS administration as evidenced from reduction in elevated thiobarbituric acid reactive substances (TBARS) and normalization of glutathione (GSH), glutathione peroxidase, superoxide dismutase (SOD), and catalase activity. Further, decrease in TNF-α expression and improvement in myocardial architecture was also observed. However, co-administration of N-nitro-L-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor, and Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor along with NaHS and ISO abrogated the beneficial effect of H(2)S differentially. Inhibition of NOS significantly (P ≤ 0.05) increased serum creatine kinase, lactate dehydrogenase, serum glutamic oxaloacetic transaminase activity and myocardial TBARS, along with significant (P ≤ 0.05) reduction of myocardial GSH, SOD, and catalase. This was followed by increase in TNF-α expression and histopathological changes. Our results revealed that H(2)S provides myocardial protection through interaction with NOS and COX-2 pathway and inhibition of NOS completely abrogates the hydrogen sulfide-induced cardioprotection in mice.

Increased Oxidative Stress and Iron Overload in Jordanian β-Thalassemic Children

β-Thalassemia (β-thal) is associated with abnormal synthesis of hemoglobin (Hb). Repeated blood transfusions in patients with β-thal major (β-TM) leads to an enhanced generation of reactive oxygen species (ROS), and subjects patients to peroxidative injury. We studied the antioxidant status and oxidative damage to children with β-thal in Jordan. Samples from 40 children with β-thal and 40 healthy controls were used. All children were under 13 years of age. Our results showed that plasma thiobarbituric acid reactive substances (TBARS) were elevated in β-thalassemic children compared to controls together with compensatory increase in superoxide dismutase (SOD) activity and decrease in catalase (CAT) activity. Elevated serum ferritin showed positive correlation with elevated liver enzyme levels except gamma glutamyl transferase (GGT), confirming liver involvement due to iron overload. Serum ferritin also showed a positive correlation with elevated TBARS and SOD, suggesting that iron overload is involed in the oxidative stress shown in cells.

Anti-obesity, antiatherogenic, anti-diabetic and antioxidant activities of J. montana ethanolic formulation in obese diabetic rats fed high-fat diet

J. montana extract in the form of ethanolic formulation is rich in polyphenols, mono- and sesquiterpenes, Essential oils, flavonoids, tri- tetra- and pentamethoxy quercetin derivatives. The present study was designed to investigate the antiobesity, antiatherogenic, anti-diabetic and antioxidant activities of J. montana using obese diabetic rats’ model. Rats received either regular diet, high-fat diet or high-fat diet with additional J. montana (150 and 300 mg/kg bw) for 8 weeks. In the preventive experiment, J. montana co-administered with a high fat diet significantly inhibited body weight gain, blood glucose, triglyceride, total cholesterol, LDL-C, vLDL-C, HDL-C, free fatty acid and atherogenic index levels in a dose dependent manner. J. montana-treated rats at doses of 150 and 300 mg/kg improved the insulin resistance index when compared to the high fat diet (HFD) control. Finally, the present study is designed to evaluate the effect of ethanolic extract of J. montana on figh fat diet induce obesity in rats. J. montana treatment (150 and 300 mg/kg bw) for 8 consecutive weeks prior to obese rats administration significantly prevented the decrease in the levels of hepatic oxidative stress biomarkers reduced Glutathione (GSH), Glutathione peroxidase (GPx), Glutathione reductase (GR), Superoxide dismutase (SOD) and Catalase (CAT). The J. montana extract, also exhibited its capacity to prevent the elevated thiobarbituric acid reactive substances (TBARS) in the liver tissue. In conclusion, the anti-obesity actions of J. montana are considered attributable to increased expression of energy expenditure-related fatty liver degradation, and decreased fatty acid synthesis and fat intake in the liver. Taken together, J. montana has potential as a preventive agent for type 2 diabetes mellitus (and possibly obesity) and deserves clinical trial in the near future.

Effect of amiloride: An Na / H exchange inhibitor in the middle cerebral artery occlusion model of focal cerebral ischemia in rats.

Purpose:The effect of pretreatment with amiloride (AML), an Na+ / H+ exchange inhibitor was studied in the middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia in rats.Materials and Methods:Male wistar rats were subjected to 2 hr of MCAO followed by 22-hr reperfusion. Grip strength, locomotor activity, and spontaneous alternation performance were assessed after 24 hr. Immediately after behavioral activities, animals were sacrificed and the oxidative stress markers were estimated in brains.Results:An elevation of thiobarbituric acid reactive substances (TBARS), reduction in glutathione, and antioxidant enzymes activities, namely glutathione-S-transferase, glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD) were observed following MCA occluded rats. Pretreatment with AML (0.91 and 1.82 mg/kg p.o) significantly reversed the MCAO-induced elevation in TBARS but could not reverse the other parameters. Paradoxically, AML further reduced the levels of GPx, GR, and SOD, but no significant changes were observed in the catalase activity, grip strength, and spontaneous alternation behavior of rats. Locomotor activity was reduced slightly but reversed on pretreatment with AML.Conclusions:Although pretreatment with single dose of AML showed reduction in oxidative stress markers, further multiple doses of AML as pre- and post-treatments are required to establish its potential to be used in cerebral ischemia.

A biochemical study on the gastroprotective effect of hydroalcoholic extract of Andrographis paniculata in rats

Aim:The aim of the present study is to evaluate the gastroprotective effect of hydroalcoholic extract of Andrographis paniculata (HAEAP) in male albino wistar rats.Materials and Methods:Rats were pretreated with HAEAP (100,200,500mg/kg b. wt for 30 days) and then gastric ulcers were induced by ethanol, aspirin, pylorus ligation and cold restraint stress models. Ulcer score was determined in all the ulcer models. pH, gastric volume, titrable acidity, pepsin, mucin, myeloperoxidase, H+K+ATPase, thiobarbituric acid reacting substances (TBARS) and antioxidant enzyme activities were assayed in ethanol-administered rats.Results:The ulcer score was found to be low in HAEAP-pretreated rats. Among the doses studied, 200 mg/kg b.wt was found to be optimum for significant ulcer reduction. The test drug significantly reduced the acidity, pepsin concentration, myeloperoxidase and H+K+ATPase activities in ethanol-administered rats. The elevated TBARS and decreased glutathione (GSH) and mucin levels observed during ulcerogenesis were found to be altered in HAEAP-received animals.Conclusions:The ulcer preventing effect of HAEAP may partly be due to its regulating effect on H+K+ATPase activity and /or mucin preserving effects. The flavonoids present in the HAEAP might be responsible for the gastroprotective action probably by maintaining the antioxidants and thiol status in the gastrointestinal tract.

Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat

The present study was carried out to evaluate the potential protective role of quercetin and curcumin against paracetamol-induced oxidative injury, liver damage and impairment of kidney function, as well as haematotoxicity in rats. Also, N-acetylcysteine was used to evaluate the potency of quercetin and curcumin. Paracetamol caused an elevation in thiobarbituric acid-reactive substances (TBARS) paralleled with significant decline in glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase activities (in plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in lung, liver and kidney). The apparent oxidative injury was associated with evident hepatic necrosis confirmed in histological examination, elevated plasma transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol reduced plasma total protein, albumin and globulin, while increased bilirubin, urea and creatinine, and induced haematotoxicity. The presence of quercetin or curcumin with paracetamol successfully mitigated the rise in TBARS and restored the activities of antioxidant enzymes compared to the group treated with both paracetamol and N-acetylcysteine. They also protected liver histology, normalized liver and kidney functions, which was more pronounced with curcumin. Therefore, it can be concluded that concomitant administration of quercetin or curcumin with paracetamol may be useful in reversing the toxicity of the drug compared to N-acetylcysteine.

Anti-ulcer role of herbomineral siddha drug — Thamira parpam on experimentally induced gastric mucosal damage in rats

Anti-ulcerogenic activity of Thamira parpam (TP) was investigated in two ulcer models (aspirin + pylorus ligation and HCl-ethanol). Aspirin-pylorus ligation (Asp 200 mg/kg-7 days + PL-4 hours) and HCl-ethanol (150 mM HCl in 70% ethanol) induction in rat resulted in elevation of thiobarbituric acid reactive substances (TBARS) and depletion of antioxidants (superoxide dismutase [SOD], glutathione [GSH], glutathione peroxidase [GPx]) with high ulcer scores (p < .01). In Asp + PL model, TP treatment showed mild inhibition on ulcer scores, changes in pH, gastric volume, total and free acidity, and elevation of TBARS and depletion of antioxidants. Compared to the ulcer-untreated rats (HCl-ethanol), the herbomineral drug TP treatment (0.5, 1, 2 mg/kg, per oral [p.o.]) attenuated the elevation of TBARS, decrease of antioxidants and nitrite (p < .05). Histopathological examinations were correlated with the antioxidant profile. In conclusion, the prophylactic cytoprotective nature of the herbomineral drug in experimentally induced ulcers could be mediated by its free radical quenching property.

Efficacy of Grape Seed Proanthocyanidins on Cardioprotection During Isoproterenol-induced Myocardial Injury in Rats

The present study was done to evaluate the role of grape seed proanthocyanidins (GSPs) in isoproterenol (ISO)-induced myocardial injury in rats. Male albino Wistar rats were pretreated with GSP (50, 100, and 150 mg/kg), 6 days a week, for 5 weeks. Induction of rats with ISO (85 mg/kg body weight, intraperitoneally) for 2 days resulted in a significant elevation of thiobarbituric acid-reactive substances in serum, mitochondrial cholesterol, triglycerides, and free fatty acids. A significant decrease was observed in serum reduced glutathione; ascorbic acid; alpha-tocopherol; ceruloplasmin; and mitochondrial cytochromes (b, c, c1, and aa3), phospholipids, and adenosine triphosphate. Pretreatment with GSP (100 and 150 mg/kg) positively altered the levels of all the parameters studied and restored normal mitochondrial function when compared with ISO-induced rats. The effect at a dose of 50 mg/kg was not promising when compared with the other 2 doses (100 and 150 mg/kg). These results confirm the efficacy of GSP in alleviating ISO-induced myocardial injury.

Protective Effects of Salicylic Acid and Vitamin C on Sulfur Dioxide-Induced Lipid Peroxidation in Mice

The antioxidant effects of exogenous salicylic acid (SA) and vitamin C (Vit C) on the oxidative stress induced by 56 mg/m3 of sulfur dioxide (SO2) in mouse livers and brains were investigated. The exposure of SO2 caused significant elevation of thiobarbituric acid-reactive substance (TBARS) levels and reduction of enzyme activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in brain and liver, accompanied by a decrease in relative growth rate, when compared with controls. Application of moderate concentrations of SA and Vit C markedly reduced the SO2-induced elevation of TBARS levels, with 5.5 mg/kg SA or 200 mg/kg Vit C being most effective. In contrast to the decrease of TBARS levels, the levels of SOD, POD, and CAT in liver and brain were significantly increased in comparison with controls. The polyacrylamide gel electrophoresis (PAGE) of total liver proteins showed that the SO2 inhalation caused a 30-kD protein band disappearance compared with the control. However, the band remained unchanged in the samples treated with 5.5 and 8.25 mg/kg SA or 100, 200, and 400 mg/kg Vit C. Therefore, this protein band may serve as a marker for the damage induced by SO2 and an additional basis for drug screening and selection.

Gastroprotective Mechanisms of Centipedic Acid, a Natural Diterpene from Egletes viscosa LESS.

This study was aimed to clarify the mechanisms of gastroprotection by centipedic acid (CPA), a natural diterpene from Egletes viscosa LESS. (Asteraceae) using ethanol-induced gastric mucosal damage in mice and gastric secretion in 4-h pylorus-ligated rats as model systems. In mice, intragastrically administered CPA (25, 50, 100 mg/kg) greatly reduced the mucosal lesions induced by 96% ethanol (0.2 ml, p.o.) by 18, 53, and 79%, respectively, whereas N-acetylcysteine (NAC, 300 mg/kg, i.p.), the reference compound produced a 50% inhibition. In 4-h pylorus-ligated rats, CPA (50 mg/kg) applied intraduodenally decreased both gastric secretory volume and total acidity. Similar to NAC, the plant diterpene effectively prevented the ethanol associated decrease in non-proteic sulfhydryls (NP-SH) and the elevated thiobarbituric acid-reactive substances (TBARS) in gastric tissue, suggesting that these compounds exert an antioxidant effect. Pretreatment of mice with indomethacin, the cyclooxygenase inhibitor but not with capsazepine, the transient receptor potential vanilloid-1 (TRPV1)-receptor antagonist greatly suppressed the gastroprotective effect of CPA. Furthermore, CPA gastroprotection was significantly attenuated in mice pretreated with L-NAME or glibenclamide the respective inhibitors of nitric oxide synthase and K(+)(ATP) channel activation. These data suggest that CPA affords gastroprotection by different and complementary mechanisms, which include a sparing effect on NP-SH reserve, and roles for endogenous prostaglandins, nitric oxide, and TRPV1-receptor and K(+)(ATP) channel activation.