Hepatic Glutathione Content Research Articles

Protective effects of the bioactive natural product N-trans-Caffeoyldopamine on hepatotoxicity induced by isoniazid and rifampicin.

In our searching for novel antioxidants from natural sources, N-trans-Caffeoyldopamine which was from natural product was found to be a potential compound for its remarkable antioxidant activity. Isoniazid (INH) and Rifampicin (RFP) is widely used for the treatment of Tuberculosis (TB) as the first line drugs, have been known to be potentially hepatotoxic and may lead to drug-induced liver injury. Oxidative stress has been regarded as the major mechanism of the hepatotoxicity. Therefore, in this study, the possible protective effects of N-trans-Caffeoyldopamine was investigated in the hepatotoxicity caused by INH and RFP in rats. Results showed that serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and hepatic malondialdehyde (MDA) content were reduced dramatically, and hepatic superoxide dismutase (SOD) activity and glutathione (GSH) content were restored remarkably by N-trans-Caffeoyldopamine co-administration, as compared to the INH-RFP treated rats (p<0.01). Moreover, the histopathological damage of liver and the number of apoptotic hepatocytes were also significantly ameliorated by the treatment. It is therefore suggested that N-trans-Caffeoyldopamine can provide a definite protective effect against acute hepatic injury caused by INH and RFP in rats, which may mainly be associated with its antioxidative effect. Mechanisms studies indicated that it inhibited the lipid peroxidation through the cytochrome P450 2E1 (CYP2E1) downregulation.

Effectiveness of activated carbon and Egyptian montmorillonite in the protection against deoxynivalenol-induced cytotoxicity and genotoxicity in rats

This study was conducted to prepare and characterize activated carbon (AC) and to evaluate its protective effect against deoxynivalenol (DON) toxicity in rats compared to Egyptian montmorillonite (EM). AC was prepared using a single-step chemical activation with phosphoric acid (H3PO4). The resulted AC has a high surface area and a high total pore volume. Male Sprague–Dawley rats were divided into 6 groups (n = 10) and treated for 3 weeks as follow: the control group, the groups fed AC or EM-supplemented diet (0.5% w/w), the group treated orally with DON (5 mg/kg b.w.) and the groups fed AC or EM-supplemented diet and treated with DON. Blood and liver samples were collected for different analyses. Treatment with DON increased liver function enzymes, lipid peroxidation, tumor necrosis factor α, DNA fragmentation, decreased hepatic glutathione content, up regulating mRNA Fas and TNF-α genes expression and increased micronucleated polychromatic erythrocytes and normochromatic erythrocytes in bone marrow. Co-treatment of DON plus AC or EM succeeded to normalize the levels of the biochemical parameters, reduced the cytotoxicity of bone marrow and ameliorated the hepatic genotoxicity. Moreover, AC was more effective than EM and has a high affinity to adsorb DON and to reduce its cytotoxicity and genotoxicity.

Effects of dietary supplementation with ferulic Acid or vitamin e individually or in combination on meat quality and antioxidant capacity of finishing pigs.

This study aimed to evaluate the effects of vitamin E (VE), ferulic acid (FA) and their combination supplementation on meat quality and antioxidant capacities of finishing pigs. Sixty barrows were randomly allocated to four experimental diets using a 2×2 factorial arrangement with 2 VE supplemental levels (0 or 400 mg/kg) and 2 FA supplemental levels (0 or 100 mg/kg) in basal diets. After 28 days, six pigs per treatment were slaughtered. The results showed that VE supplementation increased loin eye area of pigs (p<0.05) and FA supplementation increased pH45min value (p<0.05). The interaction of FA×VE was observed in shear force of longissimus dorsi muscle (p<0.05). Moreover, supplementation with VE decreased hepatic and sarcous malondialdehyde (MDA) content, increased hepatic glutathione (GSH) content and sarcous glutathione peroxidase (GSH-Px) activity (p<0.05). Additionally, supplementation with FA increased hepatic GSH-Px activity and decreased sarcous MDA content (p<0.05). However, dietary treatment did not affect the expression of genes related to nuclear factor, erythroid 2-like 2 (NFE2L2) pathway. These results suggest that dietary FA and VE could partially improve meat quality and antioxidant capacity of finishing pigs, but not by activating NFE2L2 pathway under the normal conditions of farming.

An in vivo and in vitro investigation on hepatoprotective effects of Pimpinella anisum seed essential oil and extracts against carbon tetrachloride-induced toxicity.

Protective effects of different extracts and essential oil from Pimpinella anisum L. seeds were examined against carbon tetrachloride (CCl4)-induced toxicity. The parameters such as serum transaminases, lactate dehydrogenase activity, hepatic glutathione content, liver lipid peroxidation and histopathological changes of liver were assessed as toxicity markers. In the in vitro model of this study, markers such as cell viability, cellular reduced and oxidized glutathione and lipid peroxidation in HepG2 cells were evaluated. Human liver cancer cell line HepG2 and male Sprague-Dawley rats were treated with extracts and essential oil, and markers of hepatotoxicity were investigated. The data revealed that the n-hexane extract, effectively attenuated CCl4-induced toxicity in both in vitro and in vivo models in current investigation. As the oxidative stress markers were ameliorated, it might be concluded that anise seed possesses protective effects probably due to its antioxidant constituents.

N-(β- D-Xylopyranosyl)taurine Sodium Salt Supplementation Has Beneficial Effect on the Hepatic Antioxidant System of Rats Fed a High-Fat Diet and β-Alanine.

N-(β-d-Xylopyranosyl)taurine sodium salt (T-Xyl) was newly synthesized from taurine and xylose. We hypothesized that T-Xyl would have positive effects on the hepatic antioxidant system of rats fed a high-fat diet and β-alanine. β-Alanine was administered for induction of taurine depletion by dissolving in feed water (3 % w/v). Fifty-six male Sprague-Dawley rats (4-week-old) were randomly divided into seven groups with eight rats per group and fed an experimental diet for 6 weeks (N, normal diet; HF, high-fat diet; HFT, high-fat diet + 4 mmol/kg/day taurine; HFA, high-fat diet + 3 % β-alanine; and HFTX 2,4,6, high-fat diet + 3 % β-alanine + 2, 4, 6 mmol/kg/ day T-Xyl). To investigate the effect of T-Xyl on the hepatic antioxidant system, we examined the activities of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) in serum, hepatic thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) content, and glutathione peroxidase (GPx) activity. In addition, we evaluated the histology of hepatocytes. The activity of GPT in serum was significantly lower in the HFT and HFTX groups than in the HF group (p < 0.05). TBARS content increased following administration of the HF diet, but significantly decreased upon administration of taurine and T-Xyl (p < 0.05). GPx activity was significantly higher in the HFTX4 and HFTX6 groups than in the HFA group. These results suggest that T-Xyl supplementation in rats fed a high-fat diet and β-alanine seems to have beneficial effects on the hepatic antioxidant system.

Role of vitamin B6 status on antioxidant defenses, glutathione, and related enzyme activities in mice with homocysteine-induced oxidative stress

BackgroundVitamin B6 may directly or indirectly play a role in oxidative stress and the antioxidant defense system.ObjectiveThe purpose of this study was to examine the associations of vitamin B6 status with cysteine, glutathione, and its related enzyme activities in mice with homocysteine-induced oxidative stress.DesignFour-week-old male BALB/c mice were weighed and divided into one of four dietary treatment groups fed either a normal diet (as a control group and a homocysteine group), a vitamin B6-deficient diet (as a B6-deficient group), or a B6-supplemented diet (a pyridoxine-HCl-free diet supplemented with 14 mg/kg of pyridoxine-HCl, as a B6 supplement group) for 28 days. Homocysteine thiolactone was then added to drinking water in three groups for 21 days to induce oxidative stress. At the end of the study, mice were sacrificed by decapitation and blood and liver samples were obtained.ResultsMice with vitamin B6-deficient diet had the highest homocysteine concentration in plasma and liver among groups. Significantly increased hepatic malondialdehyde levels were observed in the vitamin B6-deficient group. Among homocysteine-treated groups, mice with vitamin B6-deficient diet had the highest plasma glutathione concentration and relatively lower hepatic glutathione concentration. The glutathione peroxidase activities remained relatively stable in plasma and liver whether vitamin B6 was adequate, deficient, or supplemented.ConclusionsMice with deficient vitamin B6 intakes had an aggravate effect under homocysteine-induced oxidative stress. The vitamin B6-deficient status seems to mediate the oxidative stress in connection with the redistribution of glutathione from liver to plasma, but not further affect glutathione-related enzyme activities in mice with homocysteine-induced oxidative stress.

Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress in acetaminophen-induced hepato-renal injury.

BackgroundAcetaminophen (APAP)-induced toxicity is a predominant cause of acute hepatic and renal failure. In both humans and rodents toxicity begins with a reactive metabolite that binds to proteins. This leads to mitochondrial dysfunction and nuclear DNA fragmentation resulting in necrotic cell death. Pleurotus ostreatus (an edible oyster mushroom) is well recognized as a flavourful food, as well as a medicinal supplement. In the present study, we evaluated the role of Pleurotus ostreatus in the protection against APAP-induced hepato-renal toxicity. We also explored the mechanism by which Pleurotus ostreatus exerts its effects.MethodsNinety adult male Swiss albino mice were divided into three groups (30 mice/group). Mice were offered normal diet (control and APAP groups), or diet supplemented with 10% Pleurotus ostreatus (APAP + Pleurotus ostreatus) for 10 days. Mice were either treated with vehicle (control group, single intra-peritoneal injection.), or APAP (APAP and APAP + Pleurotus ostreatus groups, single intra-peritoneal injection, 500 mg/kg), 24 hours after the last meal.ResultsAPAP increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) glutamate dehydrogenase (GDH), creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (KIM-1), and hepatic and renal malondialdehyde (MDA) content. APAP decreased hepatic and renal glutathione (GSH) content, as well as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Supplementation with Pleurotus ostreatus significantly reduced APAP-induced elevated levels of ALT, AST, GDH, creatinine, BUN, KIM-1and MDA, while GSH level, and GSH-Px and SOD activities were significantly increased. Our findings were further validated by histopathology; treatment with Pleurotus ostreatus significantly decreased APAP-induced cell necrosis in liver and kidney tissues.ConclusionsWe report here that the antioxidant effect of Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress accompanying APAP over-dose, with subsequent clinically beneficial effects on liver and kidney tissues.

Ameliorative effect of parsley oil (Petroselinum crispum) against alcohol-induced hepatotoxicity and oxidative stress

Objective The aim of the present study was to evaluate the protective role of parsley oil in experimental alcohol-induced hepatotoxicity. Materials and methods Alcohol-administered rats were pretreated with parsley oil (50 mg/kg body weight) three times per week for 3 weeks and alcohol (10%) three times per week (during the first 2 weeks of the experiment). Results It was found that alcohol led to a marked increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transferase (γ-GT) activities. In terms of oxidative stress and the antioxidant defense system, the depleted hepatic glutathione content, glutathione-S-transferase, and catalase activities of alcohol-administered rats increased above normal levels as a result of pretreatment with parsley oil. However, whereas elevated lipid peroxidation was observed in alcohol-treated rats, pretreatment with parsley oil produced a detectable decrease in the lipid peroxidation level. Conclusion The natural plant components found in parsley could protect the liver against alcohol-induced hepatotoxicity and oxidative stress. However, further clinical studies are required to assess the safety and benefits of parsley oil in humans.

Liver injury attenuation by curcumin in a rat NASH model: an Nrf2 activation-mediated effect?

Nuclear factor-erythroid 2-related factor-2 (Nrf2) acts as a defense system in the development of nonalcoholic steatohepatitis (NASH). Curcumin is a phenolic compound with lipid regulatory, anti-oxidative, anti-inflammatory and anti-tumorigenic properties that is beneficial in defending against NASH and was recently proved to be an Nrf2 activator. The aim of this study was to evaluate whether Nrf2 activation could be involved in NASH mitigation by curcumin. Hepatic, metabolic, and inflammatory parameters, along with hepatic Nrf2 protein expression were explored in adult Sprague-Dawley rats developing high-fat-diet-induced NASH and submitted to curcumin gavage for 6 weeks. Curcumin administration led to lower degrees of hepatic steatosis and inflammation; lower levels of serum aminotransferases, lipids, and homeostasis model assessment of insulin resistance; and lower serum and hepatic contents of tumor necrosis factor-α (TNF-α), interleukin-6, and malondialdehyde. In contrast, higher hepatic contents of glutathione, heme oxygenase-1 and superoxide dismutase were observed in rats with curcumin. Moreover, Nrf2 expression in liver cell nuclei was significantly higher in rats with curcumin. Curcumin can prevent and ameliorate NASH via lipid reduction, improve insulin resistance, improve anti-inflammatory, and have antioxidant effects, possibly related to its activation of Nrf2.

Role of cytochrome P450-mediated metabolism and identification of novel thiol-conjugated metabolites in mice with phenytoin-induced liver injury

Phenytoin, 5,5-diphenylhydantoin (DPH), is widely used as an anticonvulsant agent. Severe hepatic injury rarely occurs in patients who received DPH. The development of liver injury is thought to be caused by reactive metabolites; however, the metabolites suggested to contribute to hepatotoxicity have not yet been detected in vivo and their effect on developing the liver injury is largely unknown. We recently demonstrated that DPH treatment decreased hepatic glutathione (GSH) contents, and GSH-depleted condition exacerbated DPH-induced liver injury in mice. The aim of the present study was to identify the reactive metabolite and to investigate the role of P450-mediated metabolisms in DPH-induced liver injury. We identified a novel GSH-conjugated (GS)-DPH, a conjugate of putative electrophilic arene oxide intermediate with GSH, in the bile of mice with DPH-induced liver injury. In plasma, cysteine- or N-acetylcysteine-conjugated DPH was detected, and these thiol conjugates levels were correlated with the plasma alanine aminotransferase (ALT) levels. These changes were significantly reduced by pretreatment with P450 inhibitor. Furthermore, the increases of hepatic P450 activities were in parallel with elevation of plasma thiol conjugates levels. These findings suggest that the arene oxide intermediate, which can be converted to thiol conjugates, is involved in DPH-induced liver injury.

The role of intestinal microbiota in murine models of acetaminophen-induced hepatotoxicity.

Background & AimVariations in intestinal microbiota may influence acetaminophen metabolism. This study aimed to determine whether intestinal microbiota are a source of differential susceptibility to acetaminophen-induced hepatotoxicity.MethodsConventionally housed C3H/HeH (CH) and C3H/HeH germ free (GF) mice were administered a 200mg/kg IP dose of acetaminophen. The severity of hepatotoxicity at 8 hours was assessed by histology and biochemical indices. A urinary metabolic profile was obtained using 1H-NMR. Baseline hepatic glutathione content and CYP2E1 expression were quantified. An additional group of C3H/HeJ (LPS-r) mice were assessed to determine the contribution of LPS/TLR4 signalling.ResultsBaseline glutathione levels were significantly reduced (p=0.03) in GF mice. CYP2E1 mRNA expression and protein levels were not altered. Inter-individual variability did not differ between GF and CH groups. No significant differences in the extent of hepatocellular injury (ALT or percentage necrosis) were demonstrated. However, a milder acute liver failure (ALF) phenotype was shown in GF compared with CH mice, with reduced plasma bilirubin and creatinine and increased blood glucose. Differential acetaminophen metabolism was demonstrated. GF mice displayed a higher urinary acetaminophen-sulphate:glucuronide ratio compared with CH (p=0.01). Urinary analysis showed metabolic differentiation of GF and CH groups at baseline and 8 hours(cross-validated ANOVA p=1x10-22). Interruption of TLR4 signalling in LPS-r mice had additional protective effects.ConclusionVariations in intestinal microbiota do not fully explain differential susceptibility to acetaminophen-induced hepatotoxicity. GF mice experienced some protection from secondary complications following acetaminophen overdose and this may be mediated through reduced TLR4/LPS signalling.

Mitigation of Methimazole-Induced Hepatic Injury by Taurine in Mice

Methimazole is the most widely prescribed antithyroid medication in humans. However, hepatotoxicity is a deleterious adverse effect associated with methimazole administration. No specific protective agent has been developed against this complication yet. This study was designed to investigate the role of taurine as a hepatoprotective agent against methimazole-induced liver injury in mice. Different reactive metabolites were proposed to be responsible for methimazole hepatotoxicity. Hence, methimazole-induced liver injury was investigated in intact and/or enzyme-induced animals in the current investigation. Animals were treated with methimazole (200 mg/kg, by gavage), and hepatic injury induced by this drug was investigated in intact and/or enzyme-induced groups. Markers such as lipid peroxidation, hepatic glutathione content, alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in plasma, and histopathological changes in the liver of animals were monitored after drug administration. Methimazole caused liver injury as revealed by increased plasma ALT. Furthermore, a significant amount of lipid peroxidation was detected in the drug-treated animals, and hepatic glutathione reservoirs were depleted. Methimazole-induced hepatotoxicity was more severe in enzyme-induced mice. The above-mentioned alterations in hepatotoxicity markers were endorsed by significant histopathological changes in the liver. Taurine administration (1 g/kg, i.p.) effectively alleviated methimazole-induced liver injury in both intact and/or enzyme-induced animals.

PROTECTIVE EFFECT OF ALLOPURINOL ON PARACETAMOL-INDUCED LIVER INJURY IN RATS

Background Liver injury is a major health problem that challenges not only healthcare professionals but also the pharmaceutical industry and drug regulatory agencies. Continuous exposure to certain chemotherapeutic agents, drugs, environmental toxins, viral infections and bacterial invasion within the body can trigger liver injury and eventually lead to various liver diseases. Aim: The present investigation aims to elucidate the possible hepatoprotective effect of allopurinol on liver injury induced by administration of a single dose of paracetamol (PCM) to adult male albino rats. Methodology: Animals were divided into 4 groups, each of 6 rats. The first group was kept as normal control group received (carboxy methyl cellulose 1 % + tween 80 p.o.). The second group (hepatotoxicity control group) received (750 mg/kg PCM p.o. as a single dose at day 14). The third group received (NAC; 300 mg/kg/day p.o.) on a daily basis for 14 consecutive days. The fourth group (treatment group) received allopurinol (50 mg/kg/day p.o.) also for 14 consecutive days. Method of induction of liver injury by PCM: After 13 days of pre-treatment, animals were fasted for 18 hours then administered the last protected dose at day 14. After 2 hours, PCM was administered then animals were further fasted for 24 hours. After that, animals were sacrificed and blood tissue samples were collected. Results: Administration of PCM caused liver injury in rats evidenced by significant increase in serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) content, myeloperoxidase (MPO) activity, total nitrate/nitrite (NOx) production. In addition, significant decreases in hepatic catalase (CAT) activity and hepatic glutathione (GSH) content. Treatment with N-acetyl cysteine (NAC) or allopurinol protect against liver injury as evidenced by significant decreases in hepatic MPO activity, NOx production and MDA content, In addition, significant increases in hepatic CAT activity and GSH content. Conclusion: It seems that allopurinol might be protective against liver injury in rats and is promising for further clinical trials.

Ameliorative effect of pumpkin oil (Cucurbita pepo L.) against alcohol-induced hepatotoxicity and oxidative stress in albino rats

ObjectiveThe aim of the present study was to evaluate the protective role of pumpkin oil on experimental alcohol – induced hepatotoxicity. Materials and methodsRats are divided into three groups of 10 animals each. Group one (G1) was the control group is orally given distilled water for 4 weeks. Group two (G2) is given absolute ethyl alcohol (10%) in drinking water for 4 weeks. Group three (G3) alcohol– administered rats were pretreated with pumpkin oil (50 mg/kg body weight) three times per week for three weeks and alcohol (10%) three times per week (at the first two weeks of the experiment). ResultsAlcohol caused a marked rise in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (γGT) activities. Concerning oxidative stress and antioxidant defense system, the depleted hepatic glutathione content, glutathione-S-transferase and catalase activities of alcohol-administered rats were potentially increased above normal levels as a result of pretreatment with pumpkin oil. However, while elevated lipid peroxidation was noticed in alcohol treated rats, pretreatment with pumpkin oil produced a detectable decrease in lipid peroxidation level. ConclusionThe natural plant components found in pumpkin could improve the liver against alcohol-induced liver toxicity and oxidative stress. However, further clinical studies are required to assess the safety and benefits of pumpkin oil in human beings.

Asiatic acid ameliorates hepatic lipid accumulation and insulin resistance in mice consuming a high-fat diet.

Effects of asiatic acid (AA) at 10 or 20 mg/kg/day upon hepatic steatosis in mice consuming a high-fat diet (HFD) were examined. AA intake decreased body weight, water intake, feed intake, epididymal fat, and plasma and hepatic triglyceride levels in HFD-treated mice (P < 0.05). HFD enhanced 2.85-fold acetyl coenzyme A carboxylase (ACC1), 3.34-fold fatty acid synthase (FAS), 3.71-fold stearoyl CoA desaturase (SCD)-1, 3.62-fold 3-hydroxy-3-methylglutaryl coenzyme A reductase, 2.91-fold sterol regulatory element-binding protein (SREBP)-1c, and 2.75-fold SREBP-2 expression in liver (P < 0.05). Compared with HFD groups, AA intake at two doses reduced 18.9-45.7% ACC1, 25.1-49.8% FAS, 24.7-57.1% SCD-1, and 21.8-53.3% SREBP-1c protein expression (P < 0.05). Histological results indicated AA intake at two doses reduced hepatic lipid accumulation and inflammatory infiltrate. HFD increased hepatic production of reactive oxygen species, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, as well as decreased hepatic glutathione content and glutathione peroxidase and catalase activities (P < 0.05). AA intake at two doses reversed these alterations (P < 0.05). AA intake suppressed 32.4-58.8% nuclear factor kappa (NF-κ)B p65 and 24.2-56.7% p-p38 expression (P < 0.05) and at high dose down-regulated 29.1% NF-κB p50 and 40.7% p-JNK expression in livers from HFD-treated mice. AA intake at two doses lowered plasma insulin secretion and HOMR-IR (P < 0.05). These results suggest that AA is a potent hepatic protective agent against HFD-induced hepatic injury.

Effect of dietary α-lipoic acid on the mRNA expression of genes involved in drug metabolism and antioxidation system in rat liver.

In the present study, the mRNA levels of hepatic proteins involved in the drug metabolism of rats fed α-lipoic acid were evaluated by DNA microarray and real-time PCR analyses. Experimental diets containing 0, 0·1, 0·25 and 0·5 % (w/w) α-lipoic acid were fed to four groups of rats consisting of seven animals each for 21 d. DNA microarray analysis revealed that the diet containing 0·5 % α-lipoic acid significantly (P< 0·05) increased the mRNA levels of various phase I drug-metabolising enzymes up to 15-fold and phase II enzymes up to 52-fold in an isoenzyme-specific manner. α-Lipoic acid also up-regulated the mRNA levels of some members of the ATP-binding cassette transporter superfamily, presumed to be involved in the exportation of xenobiotics, up to 6·6-fold. In addition, we observed that α-lipoic acid increased the mRNA levels of many proteins involved in antioxidation, such as members of the thiol redox system (up to 5·5-fold), metallothioneins (up to 12-fold) and haeme oxygenase 1 (1·5-fold). These results were confirmed using real-time PCR analysis, and α-lipoic acid dose dependently increased the mRNA levels of various proteins involved in drug metabolism and antioxidation. Consistent with these observations, α-lipoic acid dose dependently increased the hepatic concentration of glutathione and the activities of glutathione reductase and glutathione transferase measured using 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrates, but decreased the hepatic and serum concentrations of malondialdehyde. In conclusion, the present study unequivocally demonstrated that α-lipoic acid increases the mRNA expression of proteins involved in drug metabolism and antioxidation in the liver.

Antifibrotic activity of hesperidin against dimethylnitrosamine-induced liver fibrosis in rats

Hepatic fibrosis is a significant health problem that may progress to cirrhosis and cancer. It may be caused by viruses or chemicals such as dimethylnitrosamine, which is used as a preservative in processed meats and industrial products. The present study was designed to investigate the antifibrotic effect of hesperidin (100 or 200 mg/kg, a flavanone glycoside with potent anti-inflammatory and antioxidant activities) against liver fibrosis in rats compared to silymarin (100 mg/kg). Liver fibrosis was induced in rats using dimethylnitrosamine (10 mg/kg/day, i.p.) three times per week on alternating days for 4 weeks. After 28 days, tissue and blood samples were collected to assess the protective effect of hesperidin. Dimethylnitrosamine caused liver fibrosis as evidenced by the elevation in the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, as well as hepatic malondialdehyde content, gene expression of inducible nitric oxide synthase, α-smooth muscle actin and caspase-3. In addition, dimethylnitrosamine caused a reduction in serum total protein, albumin and hepatic glutathione content. Treatment with hesperidin (100 or 200 mg/kg) successfully ameliorated the deleterious effects of dimethylnitrosamine on all tested parameters. Our study indicates a novel protective effect of hesperidin against dimethylnitrosamine-induced liver fibrosis. Interestingly, the protection evoked by hesperidin (200 mg/kg) was superior to that of the standard silymarin.

Protective effects from Houttuynia cordata aqueous extract against acetaminophen-induced liver injury.

BackgroundProtective effects of Houttuynia cordata aqueous extract (HCAE) against acetaminophen-induced hepatotoxicity in Balb/cA mice were examined.MethodsHCAE, at 1 or 2 g/L, was added into the drinking water for 4 weeks. Acute liver injury was induced by acetaminophen treatment intraperitoneally (350 mg/kg body weight).ResultsAcetaminophen treatment significantly depleted hepatic glutathione (GSH) content, increased hepatic malonyldialdehyde (MDA), reactive oxygen species (ROS) and oxidized glutathione (GSSG) levels, and decreased hepatic activity of glutathione peroxidase (GPX), catalase and superoxide dismutase (SOD) (p<0.05). The pre-intake of HCAE alleviated acetaminophen-induced oxidative stress by retaining GSH content, decreasing MDA, ROS and GSSG production, and maintaining activity of GPX, catalase and SOD in liver (p<0.05). The pre-intake of HCAE also significantly lowered acetaminophen-induced increase in cytochrome P450 2E1 activity (p<0.05). Acetaminophen treatment increased hepatic release of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein-1 (p<0.05). HCAE intake significantly diminished acetaminophen-induced elevation of these cytokines (p<0.05).ConclusionThese results support that HCAE could provide hepato-protection

Insights in the mechanism underlying the protective effect of α-lipoic acid against acetaminophen-hepatotoxicity

Acetaminophen (APAP) is one of the most widely used analgesic antipyretic drugs and is a major cause of acute liver failure at overdose. The aim of this study is to investigate the possible protective effect of α-lipoic acid (α-LA, 20 or 100mg/kg administered simultaneously or after 1.5h) against APAP-induced hepatotoxicity in rats. Administration of APAP (1.5g/kg i.p.) resulted in elevation of serum ALT and hepatic malondialdehyde (MDA) content, as well as decrease in hepatic glutathione (GSH) content. In addition, elevation in hepatic hemeoxygenase-1 (HO-1) and NADPH oxidase expression was observed accompanied with a significant reduction in glutathione synthase and cystathionine-beta-synthase (CβS) expression. Furthermore, nuclear factor kappa-B (NF-κB) activity was enhanced in APAP-treated rats. Administration of the standard APAP antidote; N-acetylcysteine (NAC, 1200mg/kg) or α-LA (20mg/kg), simultaneously or 1.5h after APAP, ameliorated APAP-induced alterations in liver function, oxidant and inflammatory markers. Importantly, simultaneous administration of NAC or α-LA (20mg/kg) was more protective than their later administration. However, the beneficial effect of α-LA was lost at higher dose level (100mg/kg). Taken together, the beneficial effects of α-lipoic acid (20mg/kg) were comparable to those of NAC which provides a new possible treatment for APAP-induced hepatotoxicity in patients who cannot tolerate NAC. However, careful dose selection is warranted since the beneficial effects of α-LA were lost at higher doses.

Ethanol extract of lotus (Nelumbo nucifera) root exhibits an anti-adipogenic effect in human pre-adipocytes and anti-obesity and anti-oxidant effects in rats fed a high-fat diet

Lotus (Nelumbo Nucifera) root, a well-known medicinal plant in Asia, is reported to have various therapeutic benefits, including anti-diabetes, anti-hypertension, and anti-hyperlipidaemia. We hypothesized that the ethanol extract of lotus root (ELR) would exhibit an anti-adipogenic effect in human pre-adipocytes as well as anti-obesity and anti-oxidant effects in rats fed a high-fat diet. Treatment with ELR in human pre-adipocytes resulted in inhibition of lipid accumulation and attenuated expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor gamma and adipocyte marker genes, such as glucose transporter 4 and leptin. Administration of ELR resulted in a significant decrease in relative weights of adipose tissues in rats fed a high-fat diet. Consumption of a high-fat diet resulted in an increase in serum total cholesterol (TC) and triglyceride (TG) levels; however, administration of ELR resulted in a decrease in the levels of TC and TG. Administration of ELR resulted in a decrease in the level of serum leptin and insulin. Administration of ELR in rats fed a high-fat diet resulted in a decrease in hepatic thiobarbituric acid reactive substance content, elevated by a high-fat diet and an increase in superoxide dismutase activity and hepatic glutathione content. These results suggest that lotus root exerts anti-oxidant and anti-obesity effects and could be used as a functional and nutraceutical ingredient in combatting obesity-related diseases.