Liver Glutathione Levels Research Articles

Effect of Vitamin E Supplementation and High Stocking Density on the Performance and Stress Parameters of Broilers

ABSTRACT The present study was carried out to investigate the effect of dietary supplementation with vitamin E and stocking density on the mortality, body weight gain, feed conversion ratio, European production efficiency factor, heterophil/lymphocyte (H/L) ratio and liver glutathione (GSH) and malondialdehyde (MDA) levels of broilers. In total, 570 one-day-old Vencobb 400 broiler chickens were randomly assigned to three treatments, with six replicates each. G1 served as normal control and birds were provided a normal floor space (0.0465 m2/bird from day 1 to 21 and 0.0929 m2/bird from day 22 to 42) and basal diet containing vitamin E at 70 g/ton feed (n=150). G2 and G3 birds were subjected to high stocking density (0.0279 m2/bird from day 1 to 21 and 0.0557 m2/bird from day 22 to 42). G2 served as the high stocking density (HSD) control, birds were offered a basal diet with no vitamin E (n=210), whereas G3 birds were fed a basal diet containing vitamin E at 70 g/ton feed (n=210). The birds were fed with feed and water ad libitum throughout the study period. The supplementation of vitamin E to the birds subjected to HSD had a positive effect on body weight gain, feed conversion ratio (FCR), European Production Efficiency Factor (EPEF), H/L ratio, and liver GSH and MDA levels with those subjected to HSD and not supplemented with vitamin E. The results of the present study indicate that the supplementation of vitamin E at 70g/ton of feed to broilers subjected to HSD could effectively reverse the negative effects of HSD, and improve broiler performance.

In vivo assessment of polydatin, a natural polyphenol compound, on arsenic-induced free radical overproduction, gene expression, and genotoxicity.

Arsenic (As) is a well-known contaminant of global groundwater. Its exposure causes several hazardous effects on animals and human via oxidative stress. The present study examined the effect of polydatin (PD) on free radical overproduction in rats exposed to As. Thirty-five male rats randomly allocated into five equal groups. To the control group, physiological saline was given orally and to the second group only 100mg/L As was given by drinking water for 60days. The other groups were treated with As (100mg/L) and PD orally at 50, 100, and 200mg/kg/day, respectively. Treatment with As enhanced malondialdehyde level but decreased glutathione level in blood, liver, kidney, brain, lung, and heart of rats. Also, As decreased superoxide dismutase and catalase activities of erythrocyte, liver, kidney, brain, lung, and heart in rats. Furthermore, As treatment gave rise to increased DNA damage and gene expressions of interleukin 1 beta (IL-1β), nuclear factor kappa beta (NFκB), p53, and tumor necrosis factor-α (TNF-α) in the lung, brain, kidney, and liver. However, treatment of PD ameliorated As-exposed lipid peroxidation, antioxidant enzymes activities, DNA damage, gene expressions, and histopathological changes in tissues. In conclusion, PD has a dose-dependent protective effect on lipid peroxidation and antioxidant defense mechanism in rats against As exposure.

Assessment of genotoxicity and biodistribution of nano‐ and micron‐sized yttrium oxide in rats after acute oral treatment

The increasing use of yttrium oxide (Y2 O3 ) nanoparticles (NPs) entails an improved understanding of their potential impact on the environmental and human health. In the present study, the acute oral toxicity of Y2 O3 NPs and their microparticles (MPs) was carried out in female albino Wistar rats with 250, 500 and 1000mg kg-1 body weight doses. Before the genotoxicity evaluation, characterization of the particles by transmission electron microscopy, dynamic light scattering and laser Doppler velocimetry was performed. The genotoxicity studies were conducted using micronucleus and comet assays. Results showed that Y2 O3 NP-induced significant DNA damage at higher dose (1000mg kg-1 body weight) in peripheral blood leukocytes and liver cells, micronucleus formation in bone marrow and peripheral blood cells. The findings from biochemical assays depicted significant alterations in aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, superoxide dismutase, reduced glutathione, catalase and lactate dehydrogenase levels in serum, liver and kidneys at the higher dose only. Furthermore, tissue biodistribution of both particles was analyzed by inductively coupled plasma optical emission spectrometry. Bioaccumulation of yttrium (Y) in all tissues was significant and dose-, time- and organ-dependent. Moreover, Y2 O3 NP-treated rats exhibited higher tissue distribution along with greater clearance through urine whereas Y2 O3 MP-dosed animals depicted the maximum amount of Y in the feces. Hence, the results indicated that bioaccumulation of Y2 O3 NPs via its Y ions may induce genotoxic effects.

Effects of Carvacrol on Survival, Mesenteric Blood Flow, Aortic Function and Multiple Organ Injury in a Murine Model of Polymicrobial Sepsis.

Carvacrol (CRV) has strong cytoprotective, antioxidant, and anti-inflammatory properties. We aimed to demonstrate the possible protective effects of CRV on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wistar rats were allocated into the following four groups: Sham, CLP, Sham+CRV, and CLP+CRV. The animals were orally administered with CRV (80mg/kg/day) or vehicle (corn oil; 1mL/kg/day) for 7days. At the eighth day, Sham or CLP procedure was applied. Twenty hours after the operations, MBF and contractile responses of isolated aortic preparations to phenylephrine were measured. Tissue samples were obtained for biochemical and histopathological assessments. Additionally, survival rates were recorded throughout 96h. CRV administration improved the mesenteric perfusion, contractile function of aorta, and survival after CLP. CRV substantially prevented the elevations in the levels of LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) but could not prevent the elevations of AST and ALT after CLP. The decreased liver, kidney, and spleen glutathione levels and increased liver, kidney, lung, and spleen malondialdehyde levels induced by CLP were substantially restored by CRV. Also, histopathological protective effects of CRV on multiple organ damage due to CLP were observed. CRV possesses strong ameliorative effects on sepsis due to its protective effects on mesenteric perfusion and aortic function and its antioxidative and anti-inflammatory effects.

Coenzyme Q10 improves the survival, mesenteric perfusion, organs and vessel functions in septic rats

BackgroundCoenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier in the mitochondrial respiratory chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to investigate the effects of CoQ10 on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. MethodsWistar rats were divided into Sham, CLP, Sham+CoQ10, CLP+CoQ10 subgroups. CoQ10 (10mg/kg/day) or vehicle (olive oil; 1mL/kg/day) was intraperitoneally injected for 15days. At 16th day, Sham or CLP operation was performed. 20h after the operations, MABF and phenylephrine responses of isolated aortic rings were measured. Tissue samples were obtained for histopathological and biochemical evaluations. Furthermore, survival rates were monitored throughout 96h. ResultsCoQ10 prevented mesenteric hypoperfusion and aortic dysfunction induced by CLP. Survival rate was %0 at 46th h in CLP group, but in CLP+CoQ10 group it was 37.5% at the end of 96h. CLP-induced elevations of serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were blocked by CoQ10. CoQ10 restored the increased liver, lung, spleen and kidney malondialdehyde levels and as well as reduced liver and spleen glutathione levels. The protective effects of CoQ10 on multiple organ damage were also observed histopathologically. ConclusionsCoQ10 showed protective effects in sepsis due to its preservative effects on mesenteric perfusion, aortic function and also its anti-inflammatory and antioxidative effects.

Dietary luteolin attenuates chronic liver injury induced by mercuric chloride via the Nrf2/NF-κB/P53 signaling pathway in rats.

Mercury exposure is a common cause of metal poisoning which is biotransformed to highly toxic metabolites thus eliciting biochemical alterations and oxidative stress. Luteolin, a phenolic compound found in many natural products, has multiple biological functions. Our study was aimed to explore the biological effects of luteolin in a liver injury model induced in rats by mercuric chloride (HgCl2). Criteria for injury included liver enzyme, glutathione and malondialdehyde levels, histopathology, TUNEL assay, hepatocyte viability and reactive oxygen species levels. The results showed that luteolin protected against HgCl2-induced liver injury. Luteolin increased total nuclear factor-erythroid-2-related factor 2 (Nrf2) levels in the presence of HgCl2. Upregulation of its downstream factors, heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1, was also observed. This suggested that protection by luteolin against HgCl2-induced liver injury involved Nrf2 pathway activation. Luteolin also decreased expression of nuclear factor-κB (NF-κB) and P53. HgCl2 exposure led to increased Bcl-associated X protein (Bax), and decreased Bcl-2-related protein long form of Bcl-x (Bcl-xL) and B-cell leukemia/lymphoma-2 (Bcl-2) expression, leading to an increased Bax/Bcl-2 ratio. Taken together, our data suggested that decreasing oxidative stress is a protective mechanism of luteolin against development of HgCl2-induced liver injury, through the Nrf2/NF-κB/P53 signaling pathway in rats.

Toxicological assessment of tungsten oxide nanoparticles in rats after acute oral exposure.

Advances in and the rapid growth of the nanotechnology sector have escalated manufacture of nanoparticles (NPs), resulting in a significant increase in the probability of exposure of humans and wildlife to these materials. Many NPs have been found to exert genotoxicity. Therefore, genotoxicity studies are mandatory to assess the toxicity of NPs as a concern of succumbing to genetic diseases and cancers are universal. Tungsten oxide (WO3) NPs are being explored extensively in various fields. However, the toxicological data of WO3 NPs by oral route in mammals is limited. Hence, the goal of the current investigation was to evaluate the acute toxicity of WO3 NPs and microparticles (MPs) after single oral administration with 100, 500 and 1000mg/kg body weight doses in female Wistar rats. TEM, dynamic light scattering and laser Doppler velocimetry techniques were used to characterise the particles. The genotoxicity studies were conducted using comet, micronucleus and chromosomal aberration assays. Alterations in biochemical indices and metal distribution in various organs were also evaluated. The mean size of WO3 NPs and MPs by TEM was 53.2±1.91nm and 5.17±3.18μm, respectively. The results revealed a significant increase in DNA damage and micronuclei and chromosomal aberrations after exposure to 1000mg/kg dose of WO3 NPs. Significant alterations in aspartate transaminase, alanine transaminase, reduced glutathione, catalase and malondialdehyde levels in serum and liver were found only at the higher dose of WO3 NPs. Tungsten (W) biodistribution was observed in all the tissues in a dose-, time- and organ-dependent manner. In addition, the maximum concentration of W was found in the liver and the least in the brain was observed. The test substances were found to have a relatively low acute toxicity hazard. The data obtained gives preliminary information on the potential toxicity of WO3 NPs and MPs.

Effect of Solubilizers on the Androgenic Activity of Basella Alba L. (Basellaceae) in Adult Male Rats.

Purpose: Solubilizers play an important role in dissolution of pharmacological ingredients and should properly dissolve the active principle(s) while preserving its activities. This study investigated the effect of starch, gelatin, methylcellulose and polyvinylpyrrolidone 10000 in the preservation of the androgenic activity of the methanol extract Basella alba (MEBa). Methods: Different groups of male albino rats were orally given the MEBa (1 mg/kg) dissolved into either 1% gelatin (1% gel), %1 methylcellulose (1% MC) and 1% polyvinylpyrrolidone 10000 (1% PVP 10000) or 2% starch solution (2% SS) for 30 days. Thereafter, animals were sacrificed and serum testosterone and creatinine levels as well as alanine aminotransferase (ALT) activity determined. Vital and reproductive organs were dissected out and weighed, while liver thiobarbituric acid reactive substances (TBARS) and glutathione levels were determined. Results: Different treatments did not affect the animal body and organ weights. The MEBa stimulatory effect on testosterone production was preserved with 2% SS and 1% PVP 10000 as vehicles. Increased liver glutathione and TBARS levels were also observed in the animals fed with the MEBa dissolved in 2% SS and 1% Gel, respectively, while other biochemical parameters remained unchanged. Conclusion: Starch and polyvinylpyrrolidone 10000 stand as good preservation agents for MEBa androgenic activity, with starch exhibiting additional antioxidant activity through increase of glutathione levels.

Thymoquinone protects against the sepsis induced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ damage in rats.

Thymoquinone (TQ) is a potent cytoprotective, antioxidant and anti-inflammatory agent. We aimed to investigate the possible protective effects of TQ on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in a murine sepsis model induced by cecal ligation and puncture (CLP). Wistar rats were divided into the following four groups: Sham, CLP, Sham+TQ and CLP+TQ. TQ (1mg/kg/day) or vehicle (dimethyl sulfoxide, 1mL/kg/day) was intraperitoneally injected for 3 days. At 4th day Sham or CLP operation was applied. 20h after the operations, MABF and contractile responses of isolated aortic rings to phenylephrine were measured. Tissue samples were obtained for histopathological and biochemical examinations. Also, survival rates were recorded throughout 96h. TQ ameliorated mesenteric hypoperfusion and partially attenuated aortic dysfunction induced by CLP. Survival rate was %0 at 42nd h in CLP group, but in CLP+TQ group it was 33.4% at the end of 96h. Serum levels of AST, ALT, LDH, BUN, Cr and inflammatory cytokines (tumor necrosis factor-α, interleukin-1 β and interleukin-6) increased in CLP group that were prevented by TQ. The decreases in liver, spleen and kidney glutathione levels and the increases in liver, lung, kidney and spleen malondialdehyde levels induced by CLP were inhibited by TQ. The histopathological protective effects of TQ on multiple organ damage due to CLP were also observed. TQ has ameliorative effects on sepsis due to its protective effects on mesenteric perfusion, contractile function of aorta and its anti-inflammatory and antioxidative effects.

Brazilian Morus nigra Attenuated Hyperglycemia, Dyslipidemia, and Prooxidant Status in Alloxan-Induced Diabetic Rats.

Morus nigra has been used popularly for several proposes, including diabetic. In an attempt to support medicinal value, the acute hypoglycemic, hypolipidemic, and antioxidant effects of the ethanolic extract of Morus nigra (EEMn 200 or 400 mg/kg b.w.) were evaluated in normal and alloxan-induced diabetic treated for 14 days. Serum biochemical and antioxidant analysis were performed at the end of experiment. Oral glucose tolerance test was performed at 10th and 15th days. Chromatographic analysis by HPLC-DAD of EEMn was performed. Insulin was used as positive control to glycemic metabolism as well as fenofibrate to lipid metabolism. EEMn (400 mg/kg/day) reduced fasting and postprandial glycaemia, improved oral glucose tolerance, and reduced lipolysis and proteolysis in diabetic rats. EEMn decreased the blood levels of total cholesterol and increased HDL level when compared to the diabetic control rats. At higher levels, EEMn reduced triglycerides and VLDL levels in diabetic rats. Also, EEMn reduced malondialdehyde and increased the reduced glutathione levels in liver of diabetic rats. Chromatographic analysis identified the presence of the flavonoids rutin, isoquercetin, and kaempferitrin. Acute EEMn treatment reduced hyperglycemia, improved oral glucose tolerance, and minimized dyslipidemia and oxidative stress leading to a reduction in atherogenic index in alloxan-induced diabetic rats.

Celecoxib administration reduced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ injury in septic rats.

The cyclooxygenase (COX)-2 overexpression is associated with vascular injury and multiple organ failure in sepsis. However, constitutive COX-1 and basal COX-2 expressions have physiological effects. We aimed to investigate the effects of partial and selective COX-2 inhibition without affecting constitutive COX-1 and basal COX-2 activities by celecoxib on mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries, and survival in septic rats accomplished by cecal ligation and puncture (CLP). Wistar rats were allocated into Sham, CLP, Sham+celecoxib, CLP+celecoxib subgroups. 2h after Sham and CLP operations, celecoxib (0.5mg/kg) or vehicle (saline; 1mL/kg) was administered orally to rats. 18h after drug administrations, MABF and responses of isolated aortic rings to phenylephrine were measured. Tissue samples were obtained for biochemical and histopathological examinations. Furthermore, survival rate was monitored throughout 96h. Celecoxib ameliorated mesenteric hypoperfusion and partially improved aortic dysfunction induced by CLP. Survival rate was%0 at 49th h in CLP group, but in CLP+celecoxib group it was 42.8% at the end of 96h. Serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were increased in CLP group that were prevented by celecoxib. The decreases in liver and spleen glutathione levels and the increases in liver, lung, spleen and kidney malondialdehyde levels in CLP group were blocked by celecoxib. The histopathological protective effects of celecoxib on organ injury due to CLP were also observed. Celecoxib has protective effects on sepsis due to its preservative effects on mesenteric perfusion, aortic function and its anti-inflammatory and antioxidative effects.

Antisense Oligonucleotide Against Kelch-like Ech-Associated protein1 Ameliorates Liver Injury in Sickle Cell Mice

A great deal of evidence links the manifestations and associated morbidities of sickle cell disease (SCD) to ischemia/reperfusion injury and increased oxidative stress. Recent studies using humanized SCD mice show that thermal and mechanical hyperalgesia is associated with microglia activation and increased oxidative stress in the spinal cord, which are all ameliorated by treatment with antioxidants. In kidneys of SCD mice, at baseline, there is elevated heme content and increased oxidative stress (increased lipid peroxidation and severe medullary congestion). Synthesis inhibition of the antioxidant glutathione, precipitates increased sickling in kidney cortex and medulla. In SCD patients presenting with acute chest syndrome, researchers have shown that F(2)-isoprostanes, markers of oxidative injury, are significantly elevated and decline to baseline levels after exchange blood transfusions. In sickle cell patients, plasma levels of pentosidine and CML, established biomarkers of oxidative stress, correlate with the hemolytic rate, endothelial activation (adhesion molecules levels), and with the presence of hemolysis-related complications. Taken together these studies indicate that oxidative stress plays a significant role in SCD-related pain and organ injury. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of genes involved in cellular defense against oxidative stress and is constitutively inhibited by Kelch-like ECH-associated protein1 (Keap1). With increased oxidative stress, Keap1 is inactivated and Nrf2 stabilizes, translocates to the nucleus, and binds to antioxidant response elements (ARE) within promoters of genes that increase antioxidant capacity. In two recent studies, researchers have shown that genetic and pharmacologic inhibition of Keap1 ameliorates inflammation and liver and lung damage in SCD mice. Therefore, this pathway holds great promise as a possible therapeutic target in SCD. Here, we investigated the feasibility of using an antisense oligonucleotide (ASO) against Keap1 (Keap1ASO) to knockdown expression of Keap1 in SCD mice. Keap1ASO and controlASO were obtained from IONIS Pharmaceuticals (ionispharma.com). We then treated homozygous Townes (sickling) SCD mice (8-12 weeks old) with 40mg/kg Keap1ASO (n=4) or controlASO (n=4). Both controlASO and Keap1ASO were administered subcutaneously, once a week for four weeks. We showed that a 4-week treatment with Keap1ASO yielded significant Keap1 mRNA expression knockdown (Figure 1). Further, the knockdown of Keap1ASO was associated with remarkable improvement in liver injury shown by significant reduction in areas of liver necrosis in Keap1ASO-treated compared to controlASO-treated sickling mice (Figure 2). Further, these effects of Keap1ASO were not associated with significant changes in white or red blood cell counts, liver glutathione levels, transaminases or total bilirrubin. These findings are in keeping with those of others showing that genetic inhibition of Keap1 ameliorates organ injury in SCD mice without affecting erythropoiesis. Taken together, these preliminary data support the hypothesis that oxidative stress has an important role in the pathobiology of organ injury in SCD mice and that knockdown of Keap1 mRNA with Keap1ASO treatment ameliorates organ damage in SCD mice. [Display omitted] [Display omitted] DisclosuresLee:Ionis Pharmaceuticals: Employment, Equity Ownership. Hung:IONIS Pharmaceuticals: Employment, Equity Ownership. Quezado:IONIS Pharmaceuticals: Research Funding.

Manganese Chloride Induced Hepatic and Renal Toxicity in Wistar Rats

Manganese (Mn) is an essential trace metal and acts as cofactor in many cellular enzymes. But excessive concentration of the Mn is potentially toxic resulting in several disorders. The present study was designed to evaluate toxic effects of manganese chloride (MnCl 2 .4H 2 O) exposure on marker biochemical parameters, antioxidant defense system and histomorphology of liver and kidney in rats. Adult male Wistar rats were randomly divided into three groups. In group A, the rats were treated with vehicle (0.5 ml normal saline) and served as control. The rats in group B and C were exposed to MnCl 2 (50 and 100 mg/kg b.wt./day, p.o. respectively) for 120 days. The results showed significant elevation in cholesterol and triglyceride contents in liver while glycogen concentration showed significant depletion. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, urea and creatinine were significantly increased by MnCl 2 treatment. The present data also indicated that MnCl 2 significantly increased lipid peroxidation (LPO) and concomitantly decreased the levels of glutathione (GSH), ascorbic acid and superoxide dismutase (SOD) activity in both liver and kidney extracts compared to control. Histopathological study of the liver of MnCl 2 exposed rats showed dose based degenerative and atrophic changes, infiltration of mononuclear cells and dilation of sinusoids. Sections of kidney also showed dilation of glomeruli and degenerative changes in the tubules. Taken together these data suggest that MnCl 2 exposure has adverse impact on the morphology and functions of both liver and kidney in rats.

Ajoene restored behavioral patterns and liver glutathione level in morphine treated C57BL6 mice.

Oxidative stress exacerbates drug dependence induced by administration of opiate analgesics such as morphine-induced tolerance and physical dependence associated with the reduction in hepatic glutathione (GSH) level. Ajoene obtained from garlic (Allium sativum L.) has been reported for anti-tumorigenic, anti-oxidative and neuroprotective properties, however, little is known about its effect on morphine-induced dependence. Therefore, this study aimed at the effect of ajoene on physical and/or psychological dependence and liver GSH content in morphine-treated mice. Conditioned place preference (CPP) test and measurement of morphine withdrawal syndrome were performed in C57BL6 mice for behavioral experiments. Thereafter, mice were sacrificed for measurement of serum and liver GSH levels. Ajoene restored CPP and naloxone-precipitated jumping behavior in mice exposed to morphine. Moreover, the reduced level of liver GSH content in morphine treated mice was back to normal after ajoene administration. Taken together, ajoene improved behavioral patterns in mice exposed to morphine suggesting its potential therapeutic benefit against morphine-induced dependence.

Dietary potato peel extract reduces the toxicity of cholesterol oxidation products in rats

We determined the polyphenolic profiles of the potato peel by HPLC. To elucidate the effect of potato peel extract (PPE) on the toxicity of cholesterol oxidation products (COPs) in rats, a synthetic polyphenolic mixture was prepared, mimicking the composition of PPE. Six groups were treated with a control diet, an oxidized cholesterol diet, a PPE diet, an oxidized cholesterol plus PPE diet, and various doses (1–3%) of the PPE diet. After treatment, significantly increased liver glutathione and trolox equivalent antioxidant capacity levels; superoxide dismutase, catalase, and glutathione peroxidase activities; and mRNA expression were observed in the rats treated with 2% and 3% doses of the PPE diet and significantly decreased aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, creatinine, and COPs levels were observed compared with the control rats. These results demonstrated the PPE diet reduction in the long-term toxicity of COPs was significant in rats.

Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats.

Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA-nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-β1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-β1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-β1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.

The ameliorative effect of dietary barley and malted barley on hyperlipidemic rats

The present study was carried out to investigate the efficiency of barley or malted barley in ameliorating lipid profile and oxidative stress alteration caused by high fat, high cholesterol diet (HFHC).Adult male albino rats were divided into six groups; each group consisted of 12 rats. Group (1) Served as control, fed on balanced diet (without treatment);groups (2) and (3), rats were fed on balanced diet containing 10 %barley and malted barley respectively, group (4),rats were fed on HFHC (50 g lard+10 g cholesterol/kg diet) to induce hypercholesterolemia. Groups (5) and (6), rats were fed on HFHC contains 10% barley and malted barley respectively. Resultsreflected a significant depletion in all parameters of lipids profile and the percentage of change reached 22.04 % 24.87%, 25.19 %, 40.34 % , 34.11 % , 54.37 % , 54.89 % for Total lipid (TL), Total cholesterol(TC) ,Triacylglycerols (TAG) , Low density lipoprotein cholesterol (LDL-C) ,Very low density lipoprotein cholesterol (VLDL-C) ,Atherogenic index(AI) and Risk factor ratio (RF) respectively when compared with HFHC group treated with barley with an exception of high density lipoprotein cholesterol (HDL-C) showed a significant increase when compared with HFHCgroup. On the other hand the results showed a significant increment in reduced glutathione level (GSH) in blood and liver. The percentage of changes in GSH in liver showed13.82 % and 21.47 % as well as, super oxide dismutase (SOD) activity by 33.05 % and 42.39 %. while a significant decrement in malondialdehyde (MDA) in serum and liver, the percentage of decrement in liver by 38.47% and 46.36% in groups fed on HFHC diet and treated with barley or malted barley respectively when compared with group fed on HFHC(p<0.05).It can be concluded that barley or malted barley can reduce lipidsprofile and oxidative stress but malted barley is more effective than barley.

Soy isoflavones reduce acetaminophen-induced liver injury by inhibiting cytochrome P-450-mediated bioactivation and glutathione depletion and increasing urinary drug excretion in rats

Soy isoflavones (SI) are phytochemicals with various biological activities. Acetaminophen can cause acute liver injury when overdosed. In this study, to investigate the effects of SI on the metabolism and toxicity of acetaminophen in liver, rats were fed a controlled diet with or without 120 mg/kg SI-rich product for 2 weeks and were then intraperitoneally injected with acetaminophen. Cytochrome P-450 (CYP), phase II enzymes, membrane transporters, and glutathione in liver were evaluated. Acetaminophen-induced elevations in plasma alanine aminotransferase activity and decreases in liver glutathione levels were ameliorated in rats treated with SI. SI reduced hepatic CYP2E1 and CYP3A activities and acetaminophen-protein adduct contents. Hepatic UDP-glucuronosyltransferase activity and urinary acetaminophen excretion were increased by SI after acetaminophen treatment. Protein expression of multidrug-resistance-associated protein 2/3 and connexin 32 in liver, however, was not changed by SI. Our results indicate that SI-rich product may act as functional food which can reduce acetaminophen-induced hepatotoxicity.

Agomelatine reduces brain, kidney and liver oxidative stress but increases plasma cytokine production in the rats with chronic mild stress-induced depression

Agomelatine (AGOM) as an antidepressant acts both as a melatonin-receptor agonist and a selective serotonin-receptor antagonist. As a potent melatonin derived antioxidant, AGOM might modulate depression-induced lipid peroxidation and pro-inflammatory cytokines in brain, kidney and liver. The present study explores whether AGOM protects against experimental depression-induced brain, kidney and liver oxidative stress, and plasma cytokine production in rats with chronic mild stress (CMS)-induced depression. Thirty-six rats were divided into four groups. The first group was used as an untreated control. The second group received AGOM for 4weeks. The third group was exposed to chronic mild stress (CMS) of 4weeks for induction depression. The fourth group received 40mg/kg AGOM and CMS for 4weeks. Liver and kidney lipid peroxidation levels were high in the CMS group although they were low in AGOM treatments. AGOM and AGOM+CMS treatments increased the lowered glutathione peroxidase activity and reduced glutathione levels in brain, kidney and liver of CMS group. β-carotene, vitamin A and vitamin E concentrations in the brain, kidney and liver of the four groups were not changed by CMS and AGOM treatments. However, plasma TNF-α, interleukin (IL)-1β, and IL-4 levels were high in the CMS and AGOM group and their levels were further increased by the AGOM+CMS treatment. In conclusions, AGOM induced protective effects against experimental depression-induced brain, kidney, and liver oxidative injuries through regulation of the glutathione concentrations and glutathione peroxidase activity. However, plasma cytokine productions were increased by the AGOM treatment.

Tanshinone IIA protects against acetaminophen-induced hepatotoxicity via activating the Nrf2 pathway

BackgroundTanshinone IIA (Tan), the main active component of Salvia miltiorrhiza, has been demonstrated to have antioxidant activity. Acetaminophen (APAP), a widely used antipyretic and analgesic, can cause severe hepatotoxicity and liver failure when taken overdose. Oxidative stress has been reported to be involved in APAP-induced liver failure. PurposeThis study aimed to investigate the effect of Tan on APAP-induced hepatotoxicity and the underlying mechanisms involved. Study DesignC57BL/6J mice were divided into six groups: (1) control, (2) APAP group, (3) APAP+Tan (30mg/kg) group, (4) Tan (30mg/kg) group, (5) APAP+Tan (10mg/kg) group, (6) Tan (10mg/kg) group. Mice in group 3 and 5 were pre-treated with specified dose of Tan by gavage and subsequently injected with an overdose of APAP intraperitoneally (i.p., 300mg/kg). The effect of Tan on Nrf2 pathway was investigated in HepG2 cells and mice. MethodsPlasma aspartate transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), liver glutathione (GSH), glutathione transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) levels were determined after mice were sacrificed. Lipid peroxidation and histological examination were performed. The effect of Tan on the Nrf2 pathway was detected by western blotting and qRT-PCR. ResultsTan pretreatment reduced APAP-induced liver injury. Tan was able to activate Nrf2 and increase the expression levels of Nrf2 target genes, including glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H:quinine oxidoreductase 1 (NQO1) and hemeoxygenase-1 (HO-1), in a dose-dependent manner in HepG2 cells. Consistent with our observations in HepG2 cells, Tan increased nuclear Nrf2 accumulation and upregulated mRNA and protein levels of the Nrf2 target genes GCLC, NQO1 and HO-1 in C57BL/6J mice compared with mice treated with APAP alone. ConclusionsOur results demonstrate that Tan pretreatment could protect the liver from APAP-induced hepatic injury by activating the Nrf2 pathway. Tan may provide a new strategy for the protection against APAP-induced liver injury.