Effects of Epigallocatechin-3-gallate on lead-induced oxidative damage

Recent studies have shown that lead (Pb) could disrupt the prooxidant/antioxidant balance of tissue which leads to biochemical and physiological dysfunction. Epigallocatechin-3-gallate (EGCG), a catechin polyphenols component, is found to be an effective antioxidant. The present study investigated whether EGCG administration could reverse the changes on redox states in rat hippocampus caused by lead exposure. The association between redox status changes and long-term potentiation (LTP) in CA1 area of hippocampus were also examined. Wistar rats exposed to lead from postnatal day 1 were followed by 10 days of EGCG (10, 25 and 50 mg/kg) administration through intraperitoneally (ip), and the rats were sacrificed for experiments at the age of 21–23 days. The experimental results showed that glutathione (GSH) and superoxide dismutase (SOD) activity decreased accompanied with LTP amplitude decrease in CA1 area of hippocampus in the lead-exposed group. EGCG supplementation following lead intoxication resulted in increases in the GSH and SOD levels and increases in the LTP amplitude. Malondialdehyde (MDA) levels, a major lipid peroxidation byproduct, increased following lead exposure and decreased following EGCG treatment. In hippocampal neuron culture model, lead exposure (20 μM) significantly inhibited the viability of neurons which was followed by an accumulation of ROS and a decrease of mitochondrial membrane potential (ΔΨ_m). Treatment by EGCG (10–50 μM) effectively increased cell viability, decreased ROS formation and improved ΔΨ_m in hippocampal neurons exposed to lead. These observations suggest that EGCG is a potential complementary agent in the treatment of chronic lead intoxication through its antioxidative character.     

Antimycin A-induced mitochondrial apoptotic cascade is mitigated by phenolic constituents of Phyllanthus amarus aqueous extract in Hep3B cells

Antimycin A (AMA) treatment of cells blocks mitochondrial electron transport chain, and leads to elevated ROS generation, thereby causing damage to mtDNA, proteins and lipids, along with mitochondrial membrane depolarization, release of pro-apoptotic proteins into the cytoplasm, and induction of apoptosis. Prevention of such oxidative cellular damage by the aqueous extract of Phyllanthus amarus has been investigated in this study. The extract demonstrated significant potential in mitigating H₂O₂-induced membrane damage along with considerable recession in AMA-governed mitochondrial protein and lipid degradation in Hep3B cells. 8-OHdG analysis of mtDNA damage revealed substantial protective potential of the extract against mtDNA damage. SQ-PCR of selected mtDNA sequences confirmed the potential of the extract to alleviate levels of mtDNA damage. FACS analysis with JC-1 fluorescent dye established significant escalation of mitochondrial membrane potential by the extract in AMA-treated cells. Extract treatment resulted in a distinct decline in the degrees of AMA-induced release of cytochrome c and AIF into the cytoplasm along with consequent pacification of apoptosis. All protective efficiencies of the extract reported in this study were found to hold strong and significant (P < 0.05) positive correlation to its total phenolic contents, thereby proving that polyphenolic constituents of P. amarus aqueous extract mitigate oxidative stress-induced cellular degeneration and aging.     

Protective effect of isorhamnetin 3-О-β-d-glucopyranoside from Salicornia herbacea against oxidation-induced cell damage

Isorhamnetin 3-О-β-d-glucopyranoside (1) was isolated from Salicornia herbacea. The inhibitory effects of compound 1 on oxidative stress were evaluated in free-cellular and cellular systems. An increased concentration of compound 1 not only exhibited dose-dependent scavenging activities on the generation of 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl and carbon-centered radicals, but also significantly decreased levels of intracellular reactive oxygen species (ROS) in a dose-dependent manner. Further, antioxidative mechanisms by compound 1 were examined by measuring the intracellular glutathione (GSH) level and expression levels of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione reductase and heme oxygenase-1 (HO-1). Compound 1 significantly elevated GSH level as well as expression levels of antioxidant enzymes which were closely related with amount of cellular ROS. In addition, it significantly inhibited oxidative damage of purified genomic DNA and suppressed activity of myeloperoxidase (MPO), a generator of potent oxidant (hypochlorous acid), in tumor necrosis factor-α (TNF-α) stimulated human myeloid cells. Therefore, these results suggested that compound 1 has a therapeutic effectiveness in prevention of ROS-induced cellular damage and is a candidate worthy of being developed as a potential natural antioxidant related to oxidative stress.     

Lupeol protects against acetaminophen-induced oxidative stress and cell death in rat primary hepatocytes

Drug induced hepatotoxicity is a major problem where phytochemicals hold promise for its abrogation. This study was carried out to explore cytoprotective potential of lupeol, a triterpene, against acetaminophen (AAP)-induced toxicity in rat hepatocytes. AAP exposure significantly (p < 0.05) reduced cell viability, disturbed Bcl-2 family pro/anti-apoptotic protein balance, increased ROS production and altered redox homeostasis. It also induced mitochondria-mediated hepatocellular injury by significant mitochondrial depolarization, caspase-9/3 activation and subsequent DNA fragmentation. Our results suggest that lupeol pre-treatment effectively restored antioxidant enzyme levels, decreased lipid peroxidation, inhibited ROS generation and depolarization of mitochondria. Lupeol also attenuated mitochondria-mediated signaling pathway and DNA damage as evident from TUNEL assay and cell cycle studies leading to prevention of cytotoxicity. This study confirms the efficacy of lupeol, a food derived antioxidant, in abrogating ROS generation, maintaining redox balance and providing significant protection against mitochondria-mediated cell death during AAP-induced toxicity.     

Glycyrrhizic acid modulates t-BHP induced apoptosis in primary rat hepatocytes

Glycyrrhizic acid (GA) is the main bioactive ingredient of licorice (Glycyrrhiza glabra). The object of this study was to evaluate the protective effects of GA on tert-butyl hydroperoxide (t-BHP) induced oxidative injury leading to apoptosis in cultured primary rat hepatocytes. Throughout the study silymarin was used as positive control. Molecular mechanisms involved in apoptotic pathways induced in hepatocytes by t-BHP at 250 μM were explored in detail. DNA fragmentation, activation of caspases and cytochrome c release were demonstrated. In addition, changes in the mitochondrial membrane potential and ROS generation were detected confirming involvement of mitochondrial pathway. Pre-treatment with GA (4 μg) protected the hepatocytes against t-BHP induced oxidative injury and the results were comparable to the pre-treatment with positive control, i.e. silymarin. The protective potential against cell death was achieved mainly by preventing intracellular GSH depletion, decrease in ROS formation as well as inhibition of mitochondrial membrane depolarization. GA was found to modulate critical end points of oxidative stress induced apoptosis and could be beneficial against liver diseases where oxidative stress is known to play a crucial role.     

Polyphenolic fraction of Lonicera caerulea L. fruits reduces oxidative stress and inflammatory markers induced by lipopolysaccharide in gingival fibroblasts

The most common oral diseases have a microbial aetiology. Pathogenic bacteria liberate a number of irritating agents including a lipopolysaccharide (LPS) that activates pro-inflammatory cytokines promoting increased activity of polymorphonucleocytes (PMN). Release of PMN-derived free radicals into an infected gingival area affects gums, periodontal ligaments and alveolar bone. Berries of Lonicera caerulea L. (blue honeysuckle) are rich in phenolics, particularly phenolic acids, flavonoids and anthocyanins that have multiple biological activities in vitro and in vivo such as antiadherence, antioxidant and anti-inflammatory. Studies have shown that polyphenols suppress a number of LPS-induced signals and thus could be effective against gingivitis. Here we assessed effects of the polyphenolic fraction of L. caerulea fruits (PFLC; containing 77% anthocyanins) on LPS-induced oxidative damage and inflammation in human gingival fibroblasts. Application of PFLC (10–50 μg/ml) reduced reactive oxygen species (ROS) production, intracellular glutathione (GSH) depletion as well as lipid peroxidation in LPS-treated cells. PFLC treatment also inhibited LPS-induced up-regulation of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) and it suppressed expression of cyclooxygenase-2 (COX-2). The effects are presumably linked to its antioxidant and anti-inflammatory activities and suggest its use in attenuating the inflammatory process, including periodontal disease.     

Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation.     

Effects of acetaminophen on reactive oxygen species and nitric oxide redox signaling in kidney of arsenic-exposed rats

We examined whether acetaminophen could alter renal oxidative stress induced by arsenic; also whether withdrawal of acetaminophen treatment can increase susceptibility of kidney to arsenic toxicity. Acetaminophen (400 and 1600 mg/kg) was co-administered orally to rats for 3 days after preexposure to arsenic (25 ppm) for 28 days (Phase-I) and thereafter, acetaminophen was withdrawn, but arsenic exposure was continued for another 28 days (Phase-II). Acetaminophen enhanced arsenic-induced lipid peroxidation, GSH depletion and ROS production and further decreased superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities. Increased peroxidation did not alter kidney weight, but increased serum urea nitrogen and creatinine. Arsenic did not alter basal, iNOS-mediated NO production or iNOS expression. Arsenic decreased cNOS-mediated NO release and eNOS expression in Phase-II. Acetaminophen increased their expressions and NO production in Phase-I. In Phase-II, arsenic-mediated effects on NO remained mostly unaffected with acetaminophen. Results reveal that acetaminophen enhanced the risk of arsenic-mediated oxidative stress in kidney. Discontinuation of acetaminophen administration also increased the susceptibility of kidney to nephrotoxic effect of arsenic. It appeared ROS were primarily responsible for oxidative stress in both the phases. NO may have a minor role in Phase-I, but does not contribute to redox signaling mechanism in Phase-II.     

Protective effects of Forsythia suspensa extract against oxidative stress induced by diquat in rats

Forsythia suspensa extract has been proved as a potential antioxidant in the recent years. The present study was undertaken to obtain the optimal antioxidant fraction in vitro and examine its antioxidative potential against diquat-induced oxidative stress in male Sprague Dawley rats in vivo. In vitro, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging experiment indicated that the CH₂Cl₂ fraction of F. suspensa (FSC) exerted the strongest scavenging activities; forsythoside A, forythialan A and phillygenin from it might be the major antioxidant constituents. In vivo, pretreatment of rats with different doses of FSC (25, 50 and 100 mg/kg bw) and vitamin C (100 mg/kg bw, positive control) for 15 days significantly lowered the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in plasma compared to the negative control group. Also, FSC significantly increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the levels of glutathione (GSH) in plasma, liver and kidney whereas it decreased the levels of malondialdehyde (MDA) in plasma and kidney. Moreover, the protective effect of FSC (100 mg/kg bw) was better than vitamin C. These results revealed that FSC exerted a protective effect against diquat-induced oxidative stress and is worthy of becoming a potential dietary antioxidant.     

Fish oil prophylaxis attenuates rotenone-induced oxidative impairments and mitochondrial dysfunctions in rat brain

Studies describing the potential of fish oil (FO) prophylaxis to render neuroprotection in experimental model/s are limited. In the present study, we have examined the propensity of FO supplements to modulate endogenous markers of oxidative stress and attenuate neurotoxicant-induced oxidative stress and mitochondrial dysfunctions in rat brain. Prepubertal male rats given FO supplements (oral, 2 and 4 mL/kg bw/day, for 30 days) showed no alterations in malondialdehyde and reactive oxygen species in brain regions. However, FO supplements significantly enhanced the GSH levels in all brain regions examined, while differential effect was discernible in the activity levels of antioxidant enzymes. Further, we investigated whether FO prophylaxis could offset Rotenone (ROT, a well known neurotoxicant) induced early oxidative stress and mitochondrial dysfunctions. While ROT elicited marked oxidative stress as evidenced by the elevated levels of malondialdehyde, hydroperoxides and protein carbonyls in the cerebellum, FO prophylaxis significantly attenuated the effect. FO prophylaxis offered varying degree of protection against ROT-induced mitochondrial dysfunctions. Collectively, our findings in the ROT model allow us to hypothesize that the prophylactic protection offered by FO may be due to its ability to enhance GSH levels, antioxidant machinery, offset protein oxidation and specific modulatory effects on brain mitochondria.     

Preventive effects of a purified extract isolated from Salvia miltiorrhiza enriched with tanshinone I,tanshinone IIA and cryptotanshinone on hepatocyte injury in vitro and in vivo

Salvia miltiorrhiza is traditionally used to treat liver disease in Asia. In this study, we tested the ability of a purified extract of S. miltiorrhiza (PF2401-SF) and its constituents, tanshinone I, tanshinone IIA, and cryptotanshinone, to protect against acute and subacute liver damage induced by carbon tetrachloride by measuring serum transaminase levels, the reduced form of glutathione (GSH), antioxidant enzyme activities, and lipid peroxidation levels in the liver. We also evaluated their ability to protect primary cultured rat hepatocytes from tertiary-butylhydroperoxide (tBH) or d-galactosamine (GalN). PF2401-SF was protective at 50–200 mg/kg per day in acute liver injury and 25–100 mg/kg per day in subacute liver injury. Tanshinone I, tanshinone IIA, and cryptotanshinon (40 μM), inhibited lactate dehydrogenase leakage, GSH depletion, lipid peroxidation and free radical generation in vitro. PF2401-SF and its major constituents, tanshinone I, tanshinone IIA and cryptotanshinone, can protect against liver toxicity in vivo and in vitro due to its antioxidant effects.     

Clerodendron glandulosum.Coleb extract ameliorates high fat diet/fatty acid induced lipotoxicity in experimental models of non-alcoholic steatohepatitis

This study evaluates the protective role of Clerodendron glandulosum.Coleb (CG) aqueous extract against high fat diet/fatty acid induced lipotoxicity in experimental models of non-alcoholic steatohepatitis (NASH). Supplementation of NASH mice with CG extract (1% and 3% in high fat diet for 16 weeks) prevented high fat diet induced elevation in liver enzymes, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status and histopathological damage to hepatocytes. Furthermore, results from in vitro study indicates, addition of CG extract (20–200 μg/ml for 24 h) to HepG2 cells minimizes oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that CG extract has the potential of preventing high fat/fatty acid induced NASH.     

Mitochondrial aquaporin-8 knockdown in human hepatoma HepG2 cells causes ROS-induced mitochondrial depolarization and loss of viability

Human aquaporin-8 (AQP8) channels facilitate the diffusional transport of H₂O₂ across membranes. Since AQP8 is expressed in hepatic inner mitochondrial membranes, we studied whether mitochondrial AQP8 (mtAQP8) knockdown in human hepatoma HepG2 cells impairs mitochondrial H₂O₂ release, which may lead to organelle dysfunction and cell death. We confirmed AQP8 expression in HepG2 inner mitochondrial membranes and found that 72 h after cell transfection with siRNAs targeting two different regions of the human AQP8 molecule, mtAQP8 protein specifically decreased by around 60% (p < 0.05). Studies in isolated mtAQP8-knockdown mitochondria showed that H₂O₂ release, assessed by Amplex Red, was reduced by about 45% (p < 0.05), an effect not observed in digitonin-permeabilized mitochondria. mtAQP8-knockdown cells showed an increase in mitochondrial ROS, assessed by dichlorodihydrofluorescein diacetate (+ 120%, p < 0.05) and loss of mitochondrial membrane potential (− 80%, p < 0.05), assessed by tetramethylrhodamine-coupled quantitative fluorescence microscopy. The mitochondria-targeted antioxidant MitoTempol prevented ROS accumulation and dissipation of mitochondrial membrane potential. Cyclosporin A, a mitochondrial permeability transition pore blocker, also abolished the mtAQP8 knockdown-induced mitochondrial depolarization. Besides, the loss of viability in mtAQP8 knockdown cells verified by MTT assay, LDH leakage, and trypan blue exclusion test could be prevented by cyclosporin A. Our data on human hepatoma HepG2 cells suggest that mtAQP8 facilitates mitochondrial H₂O₂ release and that its defective expression causes ROS-induced mitochondrial depolarization via the mitochondrial permeability transition mechanism, and cell death.     

Acetaminophen increases the risk of arsenic‐mediated development of hepatic damage in rats by enhancing redox‐signaling mechanism

We evaluated whether the commonly used analgesic‐antipyretic drug acetaminophen can modify the arsenic‐induced hepatic oxidative stress and also whether withdrawal of acetaminophen administration during the course of long‐term arsenic exposure can increase susceptibility of liver to arsenic toxicity. Acetaminophen was co‐administered orally to rats for 3 days following 28 days of arsenic pre‐exposure (Phase‐I) and thereafter, acetaminophen was withdrawn, but arsenic exposure was continued for another 28 days (Phase‐II). Arsenic increased lipid peroxidation and reactive oxygen species (ROS) generation, depleted glutathione (GSH), and decreased superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR) activities. Acetaminophen caused exacerbation of arsenic‐mediated lipid peroxidation and ROS generation and further enhancement of serum alanine aminotransferase and aspartate aminotransferase activities. In Phase‐I, acetaminophen caused further GSH depletion and reduction in SOD, catalase, GPx and GR activities, but in Phase‐II, only GPx and GR activities were more affected. Arsenic did not alter basal and inducible nitric oxide synthase (iNOS)‐mediated NO production, but decreased constitutive NOS (cNOS)‐mediated NO release. Arsenic reduced expression of endothelial NOS (eNOS) and iNOS genes. Acetaminophen up‐regulated eNOS and iNOS expression and NO production in Phase‐I, but reversed these effects in Phase‐II. Results reveal that acetaminophen increased the risk of arsenic‐mediated hepatic oxidative damage. Withdrawal of acetaminophen administration also increased susceptibility of liver to hepatotoxicity. Both ROS and NO appeared to mediate lipid peroxidation in Phase‐I, whereas only ROS appeared responsible for peroxidative damage in Phase‐II. © 2011 Wiley Periodicals, Inc. Environ Toxicol 29: 187–198, 2014.     

Protective effect of ginger extract against bromobenzene-induced hepatotoxicity in male rats

The bromobenzene (BB)-induced hepatotoxicity comes from its reactive metabolites. The efficacy of different doses of ginger (Zingiber officinalesRose) extract in alleviating hepatotoxicity was investigated in male albino rats. Oxidative stress parameters were monitored. The drugs metabolizing enzymes; cytochrome P450 and GST, pro-inflammatory marker; COX-2 and the apoptotic marker; caspase-3 were assessed. Animals were assigned to 1 of 5 groups: control group; bromobenzene (460 mg/kg BW) alone, three animal groups 3–5 treated with different doses of ethanolic ginger extract (100, 200, 300 mg/kg BW, respectively) 2 weeks prior bromobenzene (460 mg/kg BW) treatment. Rats received orally ginger extract daily for 21 days whereas bromobenzene treatment for 7 days starting from 15th day of treatment. Oral treatment of BB was found to elicit a significant decrease in the activities of the antioxidant enzymes; SOD, GPx and the GSH level, while the activities of GR and drug metabolizing enzymes; GSTs and Cyt P450 were enhanced. Also, BB-treatment resulted in a great enhanced production of nitric oxide products and activation of COX-2 and caspase-3. Pre-treatment with different doses of ginger extract prior to BB-treatment alleviated its toxic effects on the tested parameters in the three animal groups.     

Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: Protective role of arjunolic acid

Present study investigates the beneficial role of arjunolic acid (AA) against the alteration in the cytokine levels and simultaneous activation of oxidative stress responsive signaling pathways in spleen under hyperglycemic condition. Diabetes was induced by injection of streptozotocin (STZ) (at a dose of 70 mg/kg body weight, injected in the tail vain). STZ administration elevated the levels of IL-2 as well as IFN-γ and attenuated the level of TNF-α in the sera of diabetic animals. In addition, hyperglycemia is also associated with the increased production of intracellular reactive intermediates resulting with the elevation in lipid peroxidation, protein carbonylation and reduction in intracellular antioxidant defense. Investigating the oxidative stress responsive cell signaling pathways, increased expressions (immunoreactive concentrations) of phosphorylated p65 as well as its inhibitor protein phospho IκBα and phosphorylated mitogen activated protein kinases (MAPKs) have been observed in diabetic spleen tissue. Studies on isolated splenocytes revealed that hyperglycemia caused disruption of mitochondrial membrane potential, elevation in the concentration of cytosolic cytochrome c as well as activation of caspase 3 leading to apoptotic cell death. Histological examination revealed that diabetic induction depleted the white pulp scoring which is in agreement with the reduced immunological response. Treatment with AA prevented the hyperglycemia and its associated pathogenesis in spleen tissue. Results suggest that AA might act as an anti-diabetic and immunomodulatory agent against hyperglycemia.     

Casiopeína IIgly-induced oxidative stress and mitochondrial dysfunction in human lung cancer A549 and H157 cells

Casiopeínas are a series of mixed chelate copper complexes that are being evaluated as anticancer agents. Their effects in the cell include oxidative damage and mitochondrial dysfunction, yet the molecular mechanisms leading to such effects remain unclear. We tested whether [Cu(4,7-dimethyl-phenanthroline)(glycinate)]NO₃ (Casiopeína IIgly or Cas IIgly) could alter cellular glutathione (GSH) levels by redox cycling with GSH to generate ROS and cellular oxidative stress. Cas IIgly induced a dramatic drop in intracellular levels of GSH in human lung cancer H157 and A549 cells, and is able to use GSH as source of electrons to catalyze the Fenton reaction. In both cell lines, the toxicity of Cas IIgly (2.5–5 μM) was potentiated by the GSH synthesis inhibitor l-buthionine sulfoximine (BSO) and diminished by the catalytic antioxidant manganese(III) meso-tetrakis(N,N′-diethylimidazolium-2-yl)porphyrin (MnTDE-1,3-IP⁵⁺), thus supporting an important role for oxidative stress. Cas IIgly also caused an over-production of reactive oxygen species (ROS) in the mitochondria and a depolarization of the mitochondrial membrane. Moreover, Cas IIgly produced mitochondrial DNA damage that resulted in an imbalance of the expression of the apoproteins of the mitochondrial respiratory chain, which also can contribute to increased ROS production. These results suggest that Cas IIgly initiates multiple possible sources of ROS over-production leading to mitochondrial dysfunction and cell death.     

Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2-NFκB pathways

Mangiferin, a xanthone glucoside, is well known to exhibit antioxidant, antiviral, antitumor, anti-inflammatory and gene-regulatory effects. In the present study, we isolated mangiferin from the bark of Mangifera indica and assessed its beneficial role in galactosamine (GAL) induced hepatic pathophysiology. GAL (400 mg/kg body weight) exposed hepatotoxic rats showed elevation in the activities of serum ALP, ALT, levels of triglycerides, total cholesterol, lipid-peroxidation and reduction in the levels of serum total proteins, albumin and cellular GSH. Besides, GAL exposure (5 mM) in hepatocytes induced apoptosis and necrosis, increased ROS and NO production. Signal transduction studies showed that GAL exposure significantly increased the nuclear translocation of NFκB and elevated iNOS protein expression. The same exposure also elevated TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-18 and decreased IL-10 mRNA expressions. Furthermore, GAL also decreased the protein expression of Nrf2, NADPH:quinine oxidoreductase-1, heme oxygenase-1 and GSTα. However, mangiferin administration in GAL intoxicated rats or coincubation of hepatocytes with mangiferin significantly altered all these GAL-induced adverse effects. In conclusion, the hepatoprotective role of mangiferin was due to induction of antioxidant defense via the Nrf2 pathway and reduction of inflammation via NFκB inhibition.     

Effect of 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on oxidative stress in cerebral cortex of rats

The objective of this study was to verify the effect of the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on some parameters of oxidative stress in the brain of 10-day-old rats. Cerebral cortex was incubated for 1 h in the presence or absence of 1, 10 or 30 μM of 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one and thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), nitric oxide (NO) production and the release of the cytosolic enzyme lactate dehydrogenase (LDH) were measured. The organotellurium was not capable to alter TBARS and carbonyl assays. In contrast, the compound at 10 and 30 μM provoked a reduced of protein thiol groups measured by the sulfhydryl assay. Furthermore, the activity of the antioxidant enzyme CAT (10 and 30 μM) and GPx (1, 10 and 30 μM) was reduced by the organochalcogen. On the other hand, the activity of SOD and GST were enhanced respectively by 1, 10 and 30 μM of the compound. Furthermore, NO production was also increased by 30 μM of this organochalcogen. Finally, we verified that the organotellurium was capable of enhance the LDH release at 30 μM concentration. Our findings indicate that this organotellurium compound induces in vitro oxidative stress in the cerebral cortex of rats being potentially toxic for the brain of rats.