Intermittent hypoxia, brain glyoxalase-1 and glutathione reductase-1, and anxiety-like behavior in mice

Objective: Sleep apnea has been associated with anxiety, but the mechanisms of the sleep apnea-anxiety relationship are unresolved. Sleep apnea causes oxidative stress, which might enhance anxiety-like behavior in rodents. To clarify the apnea-anxiety connection, we tested the effect of intermittent hypoxia, a model of sleep apnea, on the anxiety behavior of mice. Methods: The rodents were exposed daily to 480 one-minute cycles of intermittent hypoxia to a nadir of 7±1% inspiratory oxygen fraction or to a sham procedure with room air. After 7 days, the mice from both groups were placed in an elevated plus maze and were video recorded for 10 min to allow analysis of latency, frequency, and duration in open and closed arms. Glyoxalase-1 (Glo1) and glutathione reductase-1 (GR1) were measured in the cerebral cortex, hippocampus, and striatum by Western blotting. Results: Compared to controls, the intermittent hypoxia group displayed less anxiety-like behavior, perceived by a statistically significant increase in the number of entries and total time spent in open arms. A higher expression of GR1 in the cortex was also observed. Conclusion: The lack of a clear anxiety response as an outcome of intermittent hypoxia exposure suggests the existence of additional layers in the anxiety mechanism in sleep apnea, possibly represented by sleepiness and irreversible neuronal damage.

Anti-proliferative Effects of Androctonus amoreuxi Scorpion and Cerastes cerastes Snake Venoms on Human Prostate Cancer Cells

The present study evaluated the effects of Androctonus amoreuxi scorpion venom, Cerastes cerastes snake venom and their mixture on prostate cancer cells (PC3). An MTT assay was used to determine the anti-proliferative effect of the venoms, while quantitative real time PCR was used to evaluate the expression of apoptosis-related genes (Bax and Bcl-2). Furthermore, colorimetric assays were used to measure the levels of malondialdehyde (MDA) and antioxidant enzymes. Our results show that the venoms significantly reduced PC3 cell viability in a dose-dependent manner. On the other hand, these venoms significantly decreased Bcl-2 gene expression. Additionally, C. cerastes venom significantly reduced Bax gene expression, while A. amoreuxi venom and a mixture of A. amoreuxi & C. cerastes venoms did not alter Bax expression. Consequently, these venoms significantly increased the Bax/Bcl-2 ratio and the oxidative stress biomarker MDA. Furthermore, these venoms also increased the activity levels of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. Overall, the venoms have cytotoxic and anti-proliferative effects on PC3 cells.

Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway

BACKGROUN/OBJECTIVES: Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS: After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin F2α (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. RESULTS: Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly (P < 0.05) lower than those in the HF group without dose-dependent effect. Plasma TBARS concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly (P < 0.05) increased in the HF+BGE 1.0 and HF+BGE 1.5 groups compared to those of the HF group. The mRNA expression levels of hepatic Nrf2, NQO1, HO-1, and GSTA2 were significantly (P < 0.05) increased in the HF with BGE groups compared to those in the HF group. CONCLUSIONS: The improvements of blood glucose homeostasis and antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

Effect of etoricoxib on experimental oxidative testicular ischemia-reperfusion damage in rats induced with torsion-detorsion

Etoricoxib features antioxidant and anti-inflammatory properties concomitantly, suggesting that it may be beneficial in testicular ischemia reperfusion (I/R) damage. Our aim is to investigate the effects of etoricoxib on testicular I/R damage induced with torsion-detorsion (TD). The etoricoxib + torsion-detorsion (ETD) groups of animals were given etoricoxib in 50 and 100 mg/kg of body weight (ETD-50 and ETD-100), while the testes torsion-detorsion (TTD) and sham operation rat group (SOG) animals were given single oral doses of distilled water as a solvent. TTD, ETD-50 and ETD-100 groups were subjected to 720° degrees torsion for four hours, and detorsion for four hours. The SOG group was not subjected to this procedure. Biochemical, gene expression and histopathological analyses were carried out on the testicular tissues. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were significantly higher, and the levels of total glutathione (tGSH) and glutathione reductase (GSHRd) were significantly lower in the TTD group, compared to the ETD-50, ETD-100 and SOG groups. Etoricoxib at a dose of 100 mg/kg better prevented I/R damage than the 50 mg/kg dose. Etoricoxib may be useful in clinical practice in the reduction of I/R damage on testes caused by torsion-detorsion.

Prevention of liver cirrhosis by Silymarin

This study was designed to evaluate the effects of sylimarin supplementation on different biochemical parameters in thioacetamide induced cirrhotic rats. For this purpose 24 male Albino wistar rats were divided into four groups [n=6]. Group I, remained healthy control rats, Group II, received thioacetamide [at a dose of 200mg/kg b.w, i.p, for 12 weeks, twice a week] in first phase and saline in second phase, Group III, received thioacetamide [200mg/kg b.w, i.p for 12 weeks, twice a week] in first phase and silymarin [orally at a dosage of 200mg/kg b.w, twice a week, for 8 weeks] in second phase and Group IV, received silymarin [orally at a dosage of 200mg/kg b.w, twice a week, for 8 weeks] in first phase and saline in second phase. Biochemical analysis was evaluated by total and direct bilirubin [Retiman and Franhel, 1957, Sherlock, 1951], liver specific enzymes, antioxidant enzymes [SOD [Kono et a/., 1978], Catalase [Sinha et al, 1979], Glutathione reductase [Calberg and Mannervik, 1985] and MDA [Okhawa et al, 1979]] and plasma and intraerythrocyte sodium and potassium [Tabssum et #/., 1996]. Marked increase in total and direct bilirubin and ALT activity was the indicative markers of liver cirrhosis while reduced antioxidant activity [SOD and GSH] and increased MDA and Catalase levels and disturbed electrolyte homeostasis were observed in cirrhotic group. Silymarin supplementation markedly reduced total bilirubin and ALT activity and restored the antioxidant enzymes [SOD and GSH], MDA and catalase activity and electrolyte homeostasis. These results indicate that silymarin successively attenuates the thioacetamide induced liver cirrhosis

Biochemical Markers of Oxidative Stress in Saudi Women with Recurrent Miscarriage

This study was undertaken to investigate the antioxidant/oxidant status in recurrent miscarriage patients. Antioxidants including glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), reduced glutathione (GSH) and selenium (Se), as well as the oxidants hydrogen peroxide (H2O2), oxidised glutathione (GSSG) and lipid peroxidation were assayed in plasma, whole blood and placental tissue of non-pregnant women (NP), healthy pregnant women (HP), and recurrent miscarriage (RM) patients. Results indicated that all antioxidant activities and levels in plasma and whole blood of HP women were consistently moderately lower, and much more significantly lower in RM patients when both were compared to those seen in NP women (P<0.05 and P<0.001, respectively). Furthermore, whereas plasma antioxidant activities and levels were significantly lower in RM patients, those of whole blood and placental tissue were much more significantly lower when compared with HP women (P<0.001). Concurrent with these findings there were consistent increases of equal statistical significance and magnitude in the levels of all investigated oxidants assayed in all samples when compared in between subjects of the study as indicated above. Data thus illustrated a distinct shift in favor of oxidative reactions and reactive oxygen species (ROS) generation, and very significant decreases in the GSH/GSSG ratios in whole blood and placental tissue of RM patients when compared to HP and NP women (P<0.001). The above noted oxidative stress could have been a major causative factor of recurrent miscarriage.

Mechanisms involved in reproductive damage caused by gossypol in rats and protective effects of vitamin E

BACKGROUND: Gossypol is a chemical present in the seeds of cotton plants (Gossypium sp.) that reduces fertility in farm animals. Vitamin E is an antioxidant and may help to protect cells and tissues against the deleterious effects of free radicals. The aim of this study was to evaluate the mechanisms of reproductive toxicity of gossypol in rats and the protective effects of vitamin E. Forty Wistar rats were used, divided into four experimental groups (n = 10): DMSO/ saline + corn oil; DMSO/saline + vitamin E; gossypol + corn oil; and gossypol + vitamin E. RESULTS: Fertility was significantly reduced in male rats treated with gossypol in that a significant decrease in epididy-mal sperm count was observed (P < 0.05) and the number of offspring was significantly reduced in females mated with them (P < 0.05). This dysfunction was prevented by vitamin E. Gossypol caused a significant increase in the activity of the enzymes glutathione peroxidase (P < 0.01) and glutathione reductase (P < 0.01), but vitamin E did not reduce the enzyme activities (P > 0.05). The levels of reduced glutathione and pyridine nucleotides in testis homogen-ate were significantly reduced by gossypol (P < 0.05 and P < 0.01, respectively) and this reduction was accompanied by increased levels of oxidized glutathione (P < 0.05). Vitamin E showed a preventive effect on the changes in the levels of these substances. Gossypol significantly increased the levels of malondialdehyde (P < 0.01), a lipid peroxida-tion indicator, whereas treatment with vitamin E inhibited the action of the gossypol. Vitamin E prevented a decrease in mitochondrial ATP induced by gossypol (P < 0.05). CONCLUSIONS: This study suggests that the reproductive dysfunction caused by gossypol may be related to oxidative stress and mitochondrial bioenergetic damage and that treatment with vitamin E can prevent the infertility caused by the toxin.

Myeloperoxidase Is Associated with Insulin Resistance and Inflammation in Overweight Subjects with First-Degree Relatives with Type 2 Diabetes Mellitus

BACKGROUND: Family history of type 2 diabetes mellitus (T2DM) is one of risk factors for that in future a subject can develop diabetes. Insulin resistance (IR) is important in the pathogenesis of T2DM. There is evidence that oxidative stress plays an important role in the etiology and/or progression of diabetes. Myeloperoxidase (MPO) participates in developing of inflammation. The objective was to investigate if MPO is associated with IR and inflammation in individuals with first-degree relatives of T2DM. METHODS: Cross-sectional study in 84 overweight individuals with family history of T2DM divided in two groups according to IR, group with IR (homeostasis model assessment [HOMA] > or =2.5; n=43) and control group (CG; HOMA <2.5; n=41). Complete clinical history and a venous blood sample were collected for measuring glucose and lipids profile, insulin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), MPO, glutathione reductase (GRd), glutathione peroxidase, and superoxide dismutase. RESULTS: MPO, TNF-alpha, and IL-6 were higher in patients with IR than in CG (MPO: 308.35 [190.85 to 445.42] vs. 177.35 [104.50 to 279.85], P=0.0001; TNF-alpha: 13.46 [10.58 to 18.88] vs. 9.39 [7.53 to 11.25], P=0.0001; IL-6: 32.93 [24.93 to 38.27] vs. 15.60 [12.93 to 26.27]; P=0.0001, respectively). MPO was associated with IR (rho de Spearman=0.362, P=0.001). In the analysis of lineal regression, MPO predicts IR (beta, 0.263; t, 2.520; P=0.014). In the univariate analysis, MPO had an odds ratio of 9.880 for risk of IR (95% confidence interval, 2.647 to 36.879). CONCLUSION: MPO had relation with IR and inflammation parameters in overweight subjects with first-degree relatives of T2DM. We need studies on a casual relationship and molecular mechanisms among the increased serum MPO levels, inflammation markers, and IR.

Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-kappaB Pathways

This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-kappaB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-alpha), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-kappaB, COX-2, iNOS, TNF-alpha, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-kappaB, COX-2, iNOS, TNF-alpha, p-JNK, and p-ERK. These results indicate that DADS prevents CP-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF-kappaB and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.

Alteration of hepatic anti-oxidant systems by 4-nonylphenol, a metabolite of alkylphenol polyethoxylate detergents, in Far Eastern catfish Silurus asotus

OBJECTIVES: This study aimed to estimate the effects of 4-nonylphenol (NP), a ubiquitously present surfactant in aquatic environments, on the anti-oxidant systems of the liver in the Far Eastern catfish Silurus asotus. METHODS: Changes in biochemical parameters involved in glutathione (GSH)-related and other anti-oxidant systems were analyzed following 4 weeks of 4-NP administration (0.1 and 1.0 mg/kg diet) via a formulated diet to catfish. RESULTS: 4-NP exposure induced an elevation in hepatic lipid peroxide levels and an accompanying decrease in reduced state GSH after 2 weeks, suggesting pro-oxidant effects of the chemical in catfish. This oxidative stress was associated with an inhibition of the GSH-utilizing enzyme glutathione peroxidase at the same time point. This inhibition was restored after 4 weeks. The activities of other anti-oxidant enzymes, i.e., glutathione reductase, superoxide dismutase and catalase were increased after 4 weeks. These enzyme increases occurred more strongly at the higher 4-NP concentration (1.0 mg/kg diet). CONCLUSIONS: 4-NP given to catfish at 0.1 to 1.0 mg/kg diet, concentrations relevant to environmental levels, depletes the endogenous anti-oxidant molecule GSH and temporarily inhibits GSH-related anti-oxidant enzymes. Such declines in anti-oxidant capacity and elevated oxidative stress seem to be compensated eventually by subsequent activation of various anti-oxidant enzyme systems.

Alteration of hepatic anti-oxidant systems by 4-nonylphenol, a metabolite of alkylphenol polyethoxylate detergents, in Far Eastern catfish Silurus asotus

OBJECTIVES: This study aimed to estimate the effects of 4-nonylphenol (NP), a ubiquitously present surfactant in aquatic environments, on the anti-oxidant systems of the liver in the Far Eastern catfish Silurus asotus. METHODS: Changes in biochemical parameters involved in glutathione (GSH)-related and other anti-oxidant systems were analyzed following 4 weeks of 4-NP administration (0.1 and 1.0 mg/kg diet) via a formulated diet to catfish. RESULTS: 4-NP exposure induced an elevation in hepatic lipid peroxide levels and an accompanying decrease in reduced state GSH after 2 weeks, suggesting pro-oxidant effects of the chemical in catfish. This oxidative stress was associated with an inhibition of the GSH-utilizing enzyme glutathione peroxidase at the same time point. This inhibition was restored after 4 weeks. The activities of other anti-oxidant enzymes, i.e., glutathione reductase, superoxide dismutase and catalase were increased after 4 weeks. These enzyme increases occurred more strongly at the higher 4-NP concentration (1.0 mg/kg diet). CONCLUSIONS: 4-NP given to catfish at 0.1 to 1.0 mg/kg diet, concentrations relevant to environmental levels, depletes the endogenous anti-oxidant molecule GSH and temporarily inhibits GSH-related anti-oxidant enzymes. Such declines in anti-oxidant capacity and elevated oxidative stress seem to be compensated eventually by subsequent activation of various anti-oxidant enzyme systems.

Nigella sativa fixed and essential oil improves antioxidant status through modulation of antioxidant enzymes and immunity

The onset of 21[st] century witnessed the awareness among the masses regarding the diet-health linkages. The researchers attempted to explore traditional products/plants were in the domain of pharmacy and nutrition focussing on their health benefits. In the present research intervention, we investigate the role of Nigella sativa fixed oil [NSFO] and essential oil [NSEO] in improving antioxidant status and modulation of enzymes. The National Institute of Health [NIH] provided us 30 Sprague Dawley rats that were equally placed in three groups. The groups were fed on their respective diets [56 days] two experimental diets i.e. D[2] [NSFO @ 4.0%] and D[3] [NSEO @ 0.30%] and control. The indices pertaining to antioxidant status, antioxidant enzymes, and parameters pertaining to immunity were evaluated at 4 weeks interval. The experimental diets [NSFO@ 4.0% and NSEO@ 0.30%] modulated the activities of antioxidant enzymes i.e., catalase [CAT], superoxide dismutase [SOD], glutathione transferase [GST], glutathione reductase [GR] and glutathione peroxidase [GPx], positively. Indices of antioxidant status like tocopherols and glutathione were in linear relationship with that of GPx, GR and GST [P<0.01]. Myeloperoxidase activities were in negative correlation with GST [P<0.01] but positive correlation with some other parameters. In the nutshell, the fixed and essential oil of Nigella sativa are effective in improving the indices pertaining to antioxidant status, however, the immune boosting potential needs further clarification. However, authors are of the view that there is need to explore the molecular targets of Nigella sativa fixed and essential oils. Findings from such studies would be useful to validate this instant study for health promoting potential against diabetes mellitus and cardiovascular disorders

The effect of weight reduction on antioxidant enzymes and their association with dietary intake of vitamins A, C and E / Efeito da redução de peso sobre as enzimas antioxidantes e associação destas com a ingestão de vitaminas A, C e E

Objective Our goal was to assess the effects of weight loss on antioxidant enzymes of red blood cells and it’s relation with vitamins A, E and C intake in 30 obese women. Subjects and methods General information, anthropometric measurements, 3-day food recall, and fasting blood samples were collected from 30 obese women at the beginning of the study and after 3 months intervention. Weight loss was set at about 10% of their weight before the intervention. Results Glutathione reductase and catalase activities showed a significant increase (P < 0.01) after weight reduction, but no significant changes were seen in the superoxide dismutase and glutathione peroxidase activities. There was a positive linear correlation between daily vitamin C intake with superoxide dismutase enzyme after intervention (P = 0.004, r = 0.507). There was a negative linear correlation between vitamin E intake and glutathione peroxidase activity before intervention (P = 0.005, r = -0.5). A negative correlation was found between daily vitamin A intake and glutathione reductase enzyme before and after intervention (r = -0.385, r = -0.397, P < 0.05) respectively. No significant correlation was observed between vitamins A, C, E amounts and catalase activity. Conclusions Ten percent weight reduction can have a significant role in increasing antioxidant enzymes activities, especially glutathione reductase, and catalase enzymes in obese women. However, it is important to take into consideration a balanced amount of certain nutrients while administering a diet with limited energy. .

Objetivo Nosso objetivo foi avaliar os efeitos da perda de peso sobre as enzimas antioxidantes de eritrócitos, e a relação destas com a ingestão das vitaminas A, E e C. Sujeitos e métodos Foram coletadas informações gerais e medidas antropométricas, registro alimentar de três dias e amostras de sangue em jejum de 30 mulheres obesas no início do estudo e depois de três meses da intervenção. A perda de peso determinada antes da intervenção foi de 10% do peso. Resultados As atividades da glutationa redutase e da catalase mostraram aumento significativo (P < 0,01) depois da perda de peso, mas não houve mudanças significativas nas atividades da superóxido dismutase e da glutationa peroxidase. Foi observada uma correlação linear positiva entre a ingestão diária de vitamina C e a enzima superóxido dismutase após a intervenção (P = 0,004, r = 0,507). Houve uma correlação linear negativa entre a ingestão de vitamina E e a atividade da glutationa peroxidase antes da intervenção (P = 0,005, r = -0,5). Foi observada uma correlação negativa entre a ingestão diária de vitamina A e a enzima glutationa redutase antes e depois da intervenção (r = -0,385, r = -0,397, P < 0,05), respectivamente. Não foram observadas correlações significativas entre as vitaminas A, C, E e os níveis e a atividade da catalase. Conclusões Uma redução de 10% no peso pode ter um papel significativo no aumento da atividade das enzimas antioxidantes, especialmente na glutationa redutase e catalase em mulheres obesas. Entretanto, é importante levar em consideração uma ingestão equilibrada de certos nutrientes ao se recomendar uma dieta com níveis de energia restritos. .

Effects of 5-aminolevulinic acid (ALA)-containing supernatants from selected Rhodopseudomonas palustris strains on rice growth under NaCl stress, with mediating effects on chlorophyll, photosynthetic electron transport and antioxidative enzymes

Background: Rice is globally one of the most important food crops, and NaCl stress is a key factor reducing rice yield. Amelioration of NaCl stress was assessed by determining the growth of rice seedlings treated with culture supernatants containing 5-aminolevulinic acid (ALA) secreted by strains of Rhodopseudomonas palustris (TN114 and PP803) and compared to the effects of synthetic ALA (positive control) and no ALA content (negative control). Results: The relative root growth of rice seedlings was determined under NaCl stress (50 mM NaCl), after 21 d of pretreatment. Pretreatments with 1 μM commercial ALA and 10X diluted culture supernatant of strain TN114 (2.57 μM ALA) gave significantly better growth than 10X diluted PP803 supernatant (2.11 μM ALA). Rice growth measured by dry weight under NaCl stress ordered the pretreatments as: commercial ALA N TN114 N PP803 N negative control. NaCl stress strongly decreased total chlorophyll of the plants that correlated with non-photochemical quenching of fluorescence (NPQ). The salt stress also strongly increased hydrogen peroxide (H2O2) concentration in NaCl-stressed plants. The pretreatments were ordered by reduction in H2O2 content under NaCl stress as: commercial ALA N TN114 N PP803 N negative control. The ALA pretreatments incurred remarkable increases of total chlorophyll and antioxidative activities of catalase (CAT), ascorbate peroxide (APx), glutathione reductase (GR) and superoxide dismutase (SOD); under NaCl stress commercial ALA and TN114 had generally stronger effects than PP803. Conclusions: The strain TN114 has potential as a plant growth stimulating bacterium that might enhance rice growth in saline paddy fields at a lower cost than commercial ALA.

Protective effect of bixin on carbon tetrachloride-induced hepatotoxicity in rats

BACKGROUND: The liver is an important organ for its ability to transform xenobiotics, making the liver tissue a prime target for toxic substances. The carotenoid bixin present in annatto is an antioxidant that can protect cells and tissues against the deleterious effects of free radicals. In this study, we evaluated the protective effect of bixin on liver damage induced by carbon tetrachloride (CCl4) in rats. RESULTS: The animals were divided into four groups with six rats in each group. CCl4 (0.125 mL kg-1 body wt.) was injected intraperitoneally, and bixin (5.0 mg kg-1 body wt.) was given by gavage 7 days before the CCl4 injection. Bixin prevented the liver damage caused by CCl4, as noted by the significant decrease in serum aminotransferases release. Bixin protected the liver against the oxidizing effects of CCl4 by preventing a decrease in glutathione reductase activity and the levels of reduced glutathione and NADPH. The peroxidation of membrane lipids and histopathological damage of the liver was significantly prevented by bixin treatment. CONCLUSION: Therefore, we can conclude that the protective effect of bixin against hepatotoxicity induced by CCl4 is related to the antioxidant activity of the compound.

Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats

BACKGROUND/OBJECTIVES: This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats. MATERIALS/METHODS: Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection. RESULTS: Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC). CONCLUSIONS: Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.

Neuroprotective Effect of Steamed and Fermented Codonopsis lanceolata

Codonopsis lanceolata has been used as an herbal medicine for several lung infl ammatory diseases, such as asthma, tonsillitis, and pharyngitis. Previously, we showed the neuroprotective effect of steamed and fermented C. lanceolata (SFC) in vitro and in vivo. In the current study, the treatment of HT22 cells with SFC decreased glutamate-induced cell death, suggesting that SFC protected HT22 cells from glutamate-induced cytotoxicity. Based on these, we sought to elucidate the mechanisms of the neuroprotective effect of SFC by measuring the oxidative stress parameters and the expression of Bax and caspase-3 in HT22 cells. SFC reduced contents of ROS, Ca2+ and NO. Moreover, SFC restored contents of glutathione and glutathione reductase as well as inhibited Bax and caspase-3 activity in HT22 cells. These results indicate that steamed and fermented C. lanceolata (SFC) extract protected HT22 cells by anti-oxidative effect and inhibition of the expression of Bax and caspase-3.

Selected spices and their combination modulate hypercholesterolemia-induced oxidative stress in experimental rats

BACKGROUND: Effect of aqueous extracts of Allium sativum (garlic), Zingiber officinale (ginger), Capsicum fructensces (cayenne pepper) and their mixture on oxidative stress in rats fed high Cholesterol/high fat diet was investigated. Rats were randomly distributed into six groups (n = 6) and given different dietary/spice treatments. Group 1 standard rat chow (control), group 2, hypercholesterolemic diet plus water, and groups 3, 4, 5, 6, hypercholesterolemic diet with 0.5 ml 200 mg · kg-1 aqueous extracts of garlic, ginger, cayenne pepper or their mixture respectively daily for 4 weeks. RESULTS: Pronounced oxidative stress in the hypercholesterolemic rats evidenced by significant (p < 0.05) increase in MDA levels, and suppression of the antioxidant enzymes system in rat's liver, kidney, heart and brain tissues was observed. Extracts of spices singly or combined administered at 200 mg.kg-1 body weight significantly (p < 0.05) reduced MDA levels and restored activities of antioxidant enzymes. CONCLUSIONS: It is concluded that consumption of garlic, ginger, pepper, or their mixture may help to modulate oxidative stress caused by hypercholesterolemia in rats.

Antioxidant response and Lea genes expression under salt stress and combined salt plus water stress in two wheat cultivars contrasting in drought tolerance.

Two wheat cultivars, C306 and PBW343 contrasting in drought tolerance were compared for their antioxidant response and Lea genes’ expression under salt stress (SS) and combined stress (CS) of salt stress plus water stress during seedlings growth. The drought susceptible cultivar (PBW343) behaved different towards SS/CS than towards WS. It accumulated more dry masses in shoots, more ascorbate, had higher ascorbate to dehydroascorbate ratio, lesser dehydroascorbate, lesser malondialdehyde (MDA), more proline and higher antioxidant enzymes under SS than under WS. CS increased dry masses, ascorbate, ascorbate to dehydroascorbate ratio, antioxidant enzymes and decreased dehydroascorbate and MDA contents from levels under WS. The drought tolerant cultivar (C306) though showed higher levels of ascorbate, ascorbate to dehydroascorbate ratio, lower levels of dehydroascorbate, showed lesser dry biomasses in shoots, higher MDA and lesser ascorbate peroxidase and catalase activities under SS than under WS and these features were improved on combining WS with SS. All lea genes were induced under all stresses in both cultivars except Wrab17 in C306 only, was not induced under any stress. Eight Lea genes out of ten were induced higher under WS than SS in C306 but induced same in PBW343. Wdhn13 gene was higher salt-responsive than other lea genes in both cultivars.

Phytomodulatory potential of lycopene from Lycopersicum esculentum against doxorubicin induced nephrotoxicity.

An elevated level of serum urea and creatinine was observed in doxorubicin (DOX) treated animals indicating DOX-induced nephrotoxicity. Enhanced lipid peroxidation (LPO) in the renal tissue was accompanied by a significant decrease in the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) activities. Administration of lycopene (LycT) extracted from tomato to DOX treated mice showed a significant reduction in serum creatinine and urea levels which were associated with significantly low levels of LPO and significantly enhanced level of GSH and related antioxidant enzymes activity (GPx, GR and CAT) when compared to DOX group. Histopathological analysis revealed severe damage in the renal tissue of DOX treated animals. However, animals pretreated with LycT were observed to have reduced damage. Thus, from present results it may be inferred that lycopene may be beneficial in mitigating DOX induced nephrotoxicity in mice.