Carbon Tetrachloride-induced Hepatotoxicity In Mice Research Articles

Effects of Hydroalcoholic Extract of Lepidium Sativum L. on Carbon Tetrachloride-Induced Hepatotoxicity in Mice

Background: Carbon tetrachloride (CCl4 ) as an organic solvent causes symptoms of acute and chronic liver injury, including necrosis, fat changes, liver cancer, and cirrhosis. Lepidium sativum contains flavonoids, alkaloids, and antioxidant components.
 Objectives: This study aims to investigate the hepatic protection of L. Sativum Extract (LSE) on CCl4 -induced hepatotoxicity in mice. 
 Methods: A total of 25 male mice were randomly divided into five groups (n=5): control (olive oil), CCl4 , and 3 LSE groups. Except for the control group, all the mice received CCl4 (50%, 0.5 mL/kg) intraperitoneally twice a week for 4 weeks. The mice in the LSE groups were treated daily with LSE (200, 400, and 600 mg/kg) via IP injection. The animals were sacrificed 24 h after the last dose, and liver function parameters, such as Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Glutathione (GSH) were determined. Furthermore, 0.1 g of liver tissue was removed for histochemical analysis.
 Results: Significant differences were observed in GSH, ALP, AST, and ALT levels between the CCI4 and the control groups. Compared to the CCl4 group, LSE treatment significantly decreased plasma ALT (P<0.05), AST in all doses (P<0.001), and ALP in 600 mg/kg (P<0.001). In addition, LSE treatment significantly increased GSH in 400 mg/kg (P<0.01) and 600 mg/kg (P<0.001).
 Conclusion: LSE has hepatic protective activity against CCl4 -induced injuries. The possible anti-hepatotoxic mechanisms may be related to the presence of flavonoids, triterpenes, alkaloids, tannin, and coumarins in the LSE by inhibiting the free radicals mediated damage.

Protective Effects of Chlorogenic Acid against Carbon Tetrachloride-Induced Hepatotoxicity in Mice

The protective effects of chlorogenic acid (CGA) against liver injury were evaluated by its reduction in carbon tetrachloride (CCl4)-induced hepatic damage in ICR mice. The animals were orally given CGA (60, 100, and 200 mg/kg, respectively) or silymairn (200 mg/kg) daily with 0.3% CCl4 administration (3 mL/kg, dissolved in olive oil) after medicament treatment on the 7th day. Compared with the normal group, CCl4 caused severe impairment in liver according to the evidence of significant reduction in the level of total albumin and expansion (p < 0.05) of the activities in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), cholesterol, triglyceride (TG), and total albumin in serum, decreased the level of glutathione (GSH), and diminished the activities of catalase, superoxide dismutase (SOD), glutathione reductase (GSH-Rd), and glutathione peroxidase (GSH-Px) in liver while increasing the level of hepatic thiobarbituric acid-reactive substances (TBARS). However, oral administration of CGA or silymarin could significantly (p < 0.05) decrease the serum levels of AST, ALT, cholesterol, TG, and total albumin and elevated the serum total albumin and the activities of GSH, catalase, SOD, GSH-Rd, and GSH-Px while leading to decline the TBARS in liver compared with CCl4-intoxicated group. Moreover, histopathology displayed that CGA decreased the formation of lesions in liver resulted from CCl4. The outcomes indicate that CGA shows the efficiency hepatoprotective consequences for CCl4-incited liver injuries in mice by the elevation of the activities of antioxidant enzymes and hindrance of lipid peroxidation.

Bioactive Components and Hepatoprotective Activity of Acanthopleura vaillantii (Chiton) against Carbon Tetrachloride-Induced Hepatotoxicity in Mice

Marine animals provide a wide range of bioactive compounds that may offer new and innovative therapeutic tools for use in various diseases. In this study, the bioactive compounds in the extracts of Acanthopleura vaillantii (chiton) were identified, their antioxidant property assayed and the hepatoprotective activity evaluated in a carbon tetrachloride-induced hepatotoxicity model in mice. The gas chromatography-mass spectrometry (GC-MS) analysis identified mostly the polyphenolic compounds. The antioxidant assay showed that the chiton extract had radical scavenging activity. Intraperitoneal injection of the chiton extract in mice increased the hepatic enzymes and albumin content at the dose level of 10 mg chiton /kg of body weight. While administration of 20 mg chiton extract in mice was with the normalized serum albumin (Alb), alanine aminotransferases (ALT) and aspartate (AST). The histological examination of the liver sections from the 10 and 20 mg chitons treated groups showed substantial attenuation of the degenerative cellular changes, recovery from necrosis and reversal of liver fibrosis induced by the carbon tetrachloride intoxication.

Comparative study on Artemisia halodendron Turcz. and its two related plants by GC-MS analysis and protective effect against carbon tetrachloride-induced hepatotoxicity in mice

A rapid method had been used for comparative study on Artemisia halodendron Turcz. and its two related plants by gas phase-mass spectrometry (GC-MS). The comparison of the volatile oils obtained in three plants by GC-MS were similar in 20 compositions. However, n-Hexadecanoic acid (10.40%), Biphenyl (7.867%) and 9,12-Octadecadienoic acid (7.25%) were the predominant in the volatile oils of A. halodendron Turcz., whereas these constituents did not exist in the other two plants. And the study investigated the effect of three plants against CCl4-induced hepatotoxicity in mice. 70% ethanol extracts of A. halodendron Turcz. showed weaker protective effect than the other two plants. It suggested that they provide a basis for the identification of the A. halodendron Turcz. from the other two plants and the ethanol extract from three plants exerted a protecting effect against hepatotoxicity.

Protective effect of pilose antler peptide on carbon tetrachloride-induced hepatotoxicity in mice

The present study was designed to investigate the beneficial effects of pilose antler peptide (PAP) against carbon tetrachloride (CCl4) hepatotoxicity in mice, and explore the underlying mechanisms. In our results, animals were treated with either CCl4 and/or PAP for six consecutive weeks. The levels of inflammatory cytokines in serum and liver, hepatotoxicity markers in serum and histopathological evaluation were determined. PAP (50, 100mg/kg) significantly inhibited the CCl4-incuded overproduction of inflammatory cytokines including tumor necrosis factor α (TNF-α), cytokines interleukin-1β (IL-1β), and interleukin-6 (IL-6) in serum and liver. Animals treated with PAP exhibited lower levels of alanine transaminase (ALT) and aspartate transaminase (AST), PAP administration alleviated CCl4 induced hepatic fibrosis as manifested in histopathological records. In fact, PAP prevented the activation of TLR/NF-κB pathway, by inhibiting the expression of TLR2, TLR4 MyD88, p-NF-κBp65 and p-IκBα. In addition, PAP also significantly reversed CCl4-induced alteration of TGF-β and p-samd-3 in liver tissue. In conclusion, PAP restored CCl4-induced hepatotoxicity via TLR/NF-κB and TGF-β/samd-3 pathways.

Non-toxic Level of Acetaminophen Potentiates Carbon Tetrachloride-Induced Hepatotoxicity in Mice.

A wide range of medications are routinely used to maintain and improve human health. Hence, it is essential that we understand and predict adverse effects caused by the combined use of multiple medications. In the present study, we investigated whether the combination of carbon tetrachloride (CCl4) and acetaminophen (APAP) had a detrimental effect on the liver. Mice injected with APAP (100 mg/kg) showed no significant changes in hepatic injury markers (alanine aminotransferase and aspartate aminotransferase), histopathological findings, pro-inflammatory cytokine levels, or hepatic oxidative stress. In contrast, a single injection of CCl4 (15 mg/kg) led to a significant increase in hepatic injury, in addition to an increase in pro-inflammatory cytokine levels and oxidative stress. Co-administration of APAP and CCl4 resulted in exacerbation of these hepatic injuries. Our results suggest that a non-toxic dose of APAP has the potential to increase CCl4-induced liver damage and oxidative stress.

Seabuckthorn berry polysaccharide protects against carbon tetrachloride-induced hepatotoxicity in mice via anti-oxidative and anti-inflammatory activities.

The berries of Seabuckthorn (Hippophae rhamnoides L.) are traditional medicinal foods that have been used by Tibetans and Mongolians for thousands of years. The polysaccharides are the main components of Seabuckthorn berries, possessing immune stimulating, anti-cancer and anti-fatigue activities. The present study focused on evaluating the protective effects and mechanisms of Seabuckthorn berry polysaccharide (SP) against carbon tetrachloride (CCl4)-induced hepatotoxicity. Mice were orally administrated with 50, 100 and 200 mg kg-1 of SP once daily for 14 consecutive days prior to CCl4 challenge. Pretreatment with SP significantly decreased alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels, while increasing the levels of prealbumin (PALB) in the CCl4-challenged mice, which were accompanied by diminished liver injuries, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, increased GSH levels, and reduced malondialdehyde (MDA) content. The pretreatment with SP also markedly reduced the CCl4-induced expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS) and nitric oxide (NO). Furthermore, the pretreatment with SP decreased hepatic Toll-like receptor 4 (TLR4) expression and inhibited the phosphorylation of p38 MAPK, extracellular signal-regulated kinase (p-ERK), c-Jun N-terminal kinase (p-JNK) and nuclear factor-kappa B (NF-κB) in the CCl4-challenged mice. These results suggest that the pretreatment with SP protected against CCl4-induced liver damage via its anti-oxidative and anti-inflammatory activities. SP might be suitable for functional foods and natural drugs in preventing CCl4-induced hepatotoxicity.

Kampo formula "Hochu-ekki-to" suppressed carbon tetrachloride-induced hepatotoxicity in mice.

The aim of this study was to investigate whether pretreatment with the Japanese herbal medicine "Hochu-ekki-to" (TJ-41) has an ameliorative effect on carbon tetrachloride (CCl4)-induced hepatotoxicity through anorexia prevention. Twenty-four hours before CCl4 injection, TJ-41 or saline solution was intraperitoneally administered. Furthermore, 24h after TJ-41 injection, mice were intraperitoneally administered 1.6g/kg CCl4 or olive oil. Moreover, 24h after CCl4/olive oil injection, mice from each group were euthanized and bled for plasma analysis. Mice injected with CCl4 exhibited severe anorexia. Moreover, CCl4 increased the plasma levels of hepatic injury markers (i.e., alanine aminotransferase and aspartate aminotransferase) as well as lipid peroxidation and hepatic Ca levels. Pretreatment with TJ-41 recovered the CCl4-induced anorexia and plasma levels of the hepatic injury markers. Moreover, CCl4-induced lipid peroxidation and hepatic Ca levels decreased upon TJ-41 pretreatment. In addition, hepatic metallothionein levels in the TJ-41+CCl4-treated group were decreased by >50% compared with the levels in the TJ-41-treated group, implying that metallothionein was consumed by CCl4-induced radicals. Our results suggest that TJ-41 attenuates CCl4-induced hepatotoxicity, presumably by the induction of metallothionein, which in turn scavenges radicals induced by CCl4 exposure.

Calcium-deficient diet attenuates carbon tetrachloride-induced hepatotoxicity in mice through suppression of lipid peroxidation and inflammatory response.

The aim of this study is to investigate whether a Ca-deficient diet has an attenuating effect on carbon tetrachloride (CCl4)-induced hepatotoxicity. Four-week-old male ddY mice were fed a Ca-deficient diet for 4 weeks as a part of the experimental protocol. While hypocalcemia was observed, there was no significant change in body weight. The CCl4-exposed hypocalcemic mice exhibited a significant decrease in alanine aminotransferase and aspartate aminotransferase activities at both 6 h and 24 h even though markers of renal function remained unchanged. Moreover, lipid peroxidation was impaired and total antioxidant power was partially recovered in the liver. Studies conducted in parallel with the biochemical analysis revealed that hepatic histopathological damage was attenuated 24 h post CCl4 injection in hypocalcemic mice fed the Ca-deficient diet. Finally, this diet impaired CCl4-induced inflammatory responses. Although upregulation of Ca concentration is a known indicator of terminal progression to cell death in the liver, these results suggest that Ca is also involved in other phases of CCl4-induced hepatotoxicity, via regulation of oxidative stress and inflammatory responses.

Hepatoprotective Effect of Houttuynia cordata Thunb Extract against Carbon Tetrachloride-induced Hepatic Damage in Mice.

Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters. Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05). The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment. Further, the extract showed significant antioxidant actions by scavenging the alkyl and hydroxyl free radicals. The concentration of the extract necessary for 50% scavenging of alkyl and hydroxyl radicals was 15.5 and 410 μg/ml, respectively. H. cordata extract exhibited significant hepatoprotective property in carbon tetrachloride-induced hepatotoxicity in mice. The strong antioxidant activities possessed by the extract might be responsible for such actions.

Suppressive Effect of Kampo Formula “Juzen-taiho-to” on Carbon Tetrachloride-Induced Hepatotoxicity in Mice

The aim of the present study was to investigate whether pretreatment with the Japanese herbal medicine, "Juzen-taiho-to" (JTX), had an ameliorative effect on carbon tetrachloride (CCl4)-induced hepatotoxicity through anorexia prevention. Mice injected with CCl4 exhibited severe anorexia. Moreover, CCl4 increased the plasma levels of hepatic injury markers (i.e., alanine aminotransferase and aspartate aminotransferase), lipid peroxidation, and hepatic Ca(2+) levels. Pretreatment with JTX recovered the CCl4-induced anorexia. In addition, JTX pretreatment decreased CCl4-induced plasma levels of hepatic injury markers. Increased Ca(2+) is a known indicator of the final progression to hepatocyte death, and CCl4-induced hepatotoxicity is mainly caused by oxidative stress. The present study indicated CCl4-induced lipid peroxidation and hepatic Ca(2+) content decreased with JTX pretreatment. Our results suggest that JTX has potential to protect of CCl4-induced anorexia, and the modulation of oxidative stress.

Protective effects of alisol B 23-acetate from edible botanical Rhizoma alismatis against carbon tetrachloride-induced hepatotoxicity in mice.

Carbon tetrachloride (CCl4)-induced hepatotoxicity is a common syndrome with simultaneous severe hepatocyte death and acute cholestasis. The purpose of the present study is to investigate the hepatoprotective effect of alisol B 23-acetate (AB23A), a natural triterpenoid from edible botanical Rhizoma alismatis, on acute hepatotoxicity induced by CCl4 in mice, and further to elucidate the involvement of farnesoid X receptor (FXR), signal transducers and activators of transcription 3 (STAT3) in the hepatoprotective effect. H&E staining, BrdU immunohistochemistry and TUNEL assay were used to identify the amelioration of histopathological changes, hepatocyte proliferation and apoptosis. Real-time PCR and western blot assay were used to elucidate the mechanisms underlying AB23A hepatoprotection. The results indicated that AB23A treatment in a dose-dependent manner resulted in protection against hepatotoxicity induced by CCl4via FXR activation. Through FXR activation, AB23A promoted hepatocyte proliferation via an induction in hepatic levels of FoxM1b, Cyclin D1 and Cyclin B1. AB23A also reduced hepatic bile acids through a decrease in hepatic uptake transporter Ntcp, bile acid synthetic enzymes Cyp7a1, Cyp8b1, and an increase in efflux transporter Bsep, Mrp2 expression. In addition, AB23A induced the expression of STAT3 phosphorylation, and STAT3 target genes Bcl-xl and SOCS3, resulting in decreased hepatocyte apoptosis. In conclusion, AB23A produces a protective effect against CCl4-induced hepatotoxicity, due to FXR and STAT3-mediated gene regulation.

Protective effect of Pelargonium graveolens against carbon tetrachloride-induced hepatotoxicity in mice and characterization of its bioactive constituents by HPLC–PDA–ESI–MS/MS analysis

The hepatoprotective and antioxidant activity of Pelargonium graveolens ethanol extract (PGE) against CCl4-induced liver injury was investigated in mice. The treatment of intoxicated mice with PGE (500 and 1000 mg/kg/day p.o for 6 weeks) significantly inhibited the CCl4-induced increase in alanine aminotransferase (by 37 and 43 %, at the tested doses, respectively), aspartate aminotransferase (by 33 and 35 %), alkaline phosphatase (by 26 and 33 %), and malondialdehyde levels (by 34 and 51 %). Moreover, PGE treatment markedly increased the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase), as well as the level of reduced glutathione. A marked amelioration of the inflammatory cell infiltration and hydropic degeneration was evident in the groups treated with PGE. Notably, treatment with PGE reduced the central vein congestion more than in the silymarin-treated group. PGE was as effective as silymarin in reducing the fatty changes, Kupffer cell hyperplasia, and necrosis induced by CCl4 intoxication. These results suggest that a dietary supplement of PGE could exert a beneficial effect against oxidative stress and various liver diseases by enhancing the antioxidant defense status, reducing lipid peroxidation and protecting against the pathological changes of the liver. The hepatoprotective activity of PGE is mediated, at least in part, by the antioxidant effect of its constituents. The active constituents of PGE were identified by HPLC–PDA–ESI/MS/MS.

Hepatoprotective activity of Gentiana veitchiorum Hemsl. against carbon tetrachloride-induced hepatotoxicity in mice

AimTo study the hepatoprotective effect of methanol extract of Gentiana veitchiorum (MGV) against CCl4-induced oxidative stress and liver injury in mice. MethodThe acute hepatic model was developed by injection of 20% CCl4 in mice. ICR mice were divided into six groups, including control, CCl4, CCl4+ silymarin, and CCl4+ MGV (100, 200, and 400 mg·kg−1) groups. Hepatic enzymes including AST, ALT and ALP levels in serum, and antioxidant enzymes, including SOD, CAT and GPX activity in liver tissue, were determined. Histopathological examination and Western blot analysis were performed. ResultsOral administration of MGV at 200 and 400 mg·kg−1 for 15 days dose-dependently inhibited the serum elevations of AST, ALT, and ALP, and recovered the reduction of SOD, CAT, and GPX in liver tissue. Hematoxylin and eosin staining examination performed in liver tissues suggested that MGV treatment ameliorated histopathological changes in CCl4-induced mice. Western blotting analysis implied that MGV increased HO-1 expression and recovered TNF-α alternation. ConclusionG. veitchiorum can protect the liver against CCl4-induced damage in mice, and this hepatoprotective effect was due at least in part to its ability through scavenging CCl4-associated free radical activities. The study provided in vivo evidence that G. veitchiorum can be used as a safe, cheap, and effective agent to reduce acute liver damage, supporting its folk medicine use

Protective Effect of Red Lentil (Lens Culinaris) Extract against Carbon Tetrachloride-Induced Hepatotoxicity in Mice

Protective Effect of Red Lentil (Lens Culinaris) Extract against Carbon Tetrachloride-Induced Hepatotoxicity in Mice

Hepatoprotective and antioxidant effect of Bauhinia hookeri extract against carbon tetrachloride-induced hepatotoxicity in mice and characterization of its bioactive compounds by HPLC-PDA-ESI-MS/MS.

The hepatoprotective and antioxidant activity of Bauhinia hookeri ethanol extract (BHE) against CCl4-induced liver injury was investigated in mice. BHE was administered (500 and 1000 mg/kg/day) along with CCl4 for 6 weeks. The hepatic marker enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in the serum. The antioxidant parameters: glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), and malondialdehyde (MDA) were estimated in the liver homogenate. BHE treatment significantly inhibited the CCl4-induced increase in ALT (44 and 64%), AST (36 and 46%), ALP (28 and 42%), and MDA (39 and 51%) levels at the tested doses, respectively. Moreover, BHE treatment markedly increased the activity of antioxidant parameters GSH, GPx, GR, GST, and SOD. Histological observations confirmed the strong hepatoprotective activity. These results suggest that a dietary supplement of BHE could exert a beneficial effect against oxidative stress and various liver diseases by enhancing the antioxidant defense status, reducing lipid peroxidation, and protecting against the pathological changes of the liver. The hepatoprotective activity of BHE is mediated, at least in part, by the antioxidant effect of its constituents. The active constituents of BHE were identified by HPLC-PDA-ESI/MS/MS.

Curative and protective effects of l-arginine on carbon tetrachloride-induced hepatotoxicity in mice

l-arginine may aid in the liver detoxification and may benefit in the treatment of liver disorders such as liver injury. The present study was to investigate the possible protective and curative effects of l-arginine on carbon tetrachloride (CCl4) induced hepatotoxicity. Mice received a single dose of CCl4. l-arginine treatment was given for 6days prior or post to CCl4 injection. CCl4-intoxication caused marked liver cell necrosis with inflammatory and apoptotic lesions. l-arginine treatment reduced hepatic necrosis and inflammation. CCl4-intoxication also enhanced hepatic lipid peroxidation, decreased hepatic GSH level and inhibited the activities of antioxidant enzymes. Pre-treatment and post-treatment with l-arginine decreased lipid peroxidation and restored the antioxidant status to near normal levels. These results suggest that l-arginine administration has hepatoprotective and hepatocurative effects against CCl4 induced hepatotoxicity in mice.

Dietary Diacetylene Falcarindiol Induces Phase 2 Drug-Metabolizing Enzymes and Blocks Carbon Tetrachloride-Induced Hepatotoxicity in Mice through Suppression of Lipid Peroxidation

Falcarindiol is a diacetylenic natural product containing unique carbon-carbon triple bonds. Mice were orally administrated falcarindiol (100 mg/kg), and drug-metabolizing and antioxidant enzymes were monitored in several tissues of mice. Treatment with falcarindiol was found to increase glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 activities in liver, small intestine, kidney, and lung. No changes were observed in cytochrome P450 (CYP) 1A known to activate procarcinogens. Western blot analysis revealed that various GST subunits including GSTA4, which plays an important role in the detoxification of alkenals produced from lipid peroxides, were induced in liver, small intestine, and kidney of falcarindiol-treated mice. Additionally, we investigated the protective effects of falcarindiol against hepatotoxicity induced by carbon tetrachloride (CCl(4)) and the mechanism of its hepatoprotective effect. Pretreatment with falcarindiol prior to the administration of CCl(4) significantly suppressed both an increase in serum alanine transaminase/aspartate transaminase (ALT/AST) activity and an increase in hepatic thiobarbituric acid reactive substance levels without affecting CCl(4)-mediated degradation of CYP2E1. Formation of hexanoyl-lysine and 4-hydroxy-2(E)-nonenal-histidine adducts, lipid peroxidation biomarkers, in homogenates from the liver of CCl(4)-treated mice was decreased in the group of mice pretreated with falcarindiol. These results suggest that the protective effects of falcarindiol against CCl(4) toxicity might, in part, be explained by anti-lipid peroxidation activity associated with the induction of the GSTs including GSTA4.

Protective effects of Wu-Ling-Shen (Xylaria nigripes) on carbon tetrachloride-induced hepatotoxicity in mice

Wu-Ling-Shen, a lesser study medicinal fungus (Xylaria nigripes), is popular for treating insomnia and trauma in the traditional Chinese medicine. In this study, our aim was to examine the protective effects of X. nigripes extract on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in mice, and its content of polyphenolic constituents. The X. nigripes aqueous extract (XN-T) at 500 and 1000 mg/kg was given intragastrically to mice for 9 consecutive days, followed by receiving subcutaneously 2 mL/kg of 40% CCl4 in olive oil to induce hepatotoxicity. Blood and liver tissues were collected for biochemical and histological analyses. Analysis of polyphenolic compounds was performed by RP-HPLC. Results showed that XN-T at 500 and 1000 mg/kg significantly prevented the elevation of serum glutamate oxalate transaminase (sGOT), serum glutamate pyruvate transaminase (sGPT), and liver thiobarbituric acid reactive substances (TBARS) levels, and caused an increase in the liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) concentrations, as well as serum total antioxidant activity in the CCl4-induced hepatotoxicated mice. It was as good as silymarin (100 mg/kg) in normalization of oxidative stress parameters. Furthermore, liver histological observation also showed an obvious amelioration in the liver conditions in XN-T-treated animals. XN-T was found to contain a higher level of epicatechin, catechin, and p-coumaric acid. These results conclude that XN exerts effective protection against CCl4-induced liver injury in mice, and its mechanism of action could be through the effects of antioxidants on reducing the oxidative stress.

Antifibrotic activity of anthocyanidin delphinidin in carbon tetrachloride-induced hepatotoxicity in mice

The aim of this study was to investigate the hepatoprotective effects of anthocyanidin delphinidin in carbon tetrachloride (CCl 4)-induced liver fibrosis in mice. Male Balb/C mice were treated with CCl 4 dissolved in olive oil (20%, v/v, 2 mL/kg) intraperitoneally (i.p.), twice a week for 7 weeks. Delphinidin was administered i.p. once daily for next 2 weeks, in doses of 10 and 25 mg/kg of body weight. The CCl 4 control group has been observed for spontaneous reversion of fibrosis. CCl 4-administration induced an elevation in serum transaminase and alkaline phosphatase levels and increased oxidative stress in the liver. Delphinidin has successfully attenuated oxidative stress, increased matrix metalloproteinase-9 and metallothionein I/II expression and restored hepatic architecture. Furthermore, the overexpression of tumor necrosis factor-α and transforming growth factor-β1 has been withdrawn by delphinidin. Concomitantly, the expression of α-smooth muscle actin indicated returning of hepatic stellate cells (HSC) into inactive state. Our results suggest the therapeutic effects of delphinidin in CCl 4-induced liver fibrosis by promoting extracellular matrix degradation, HSC inactivation and down-regulation of fibrogenic stimuli, with strong enhancement of hepatic regenerative capability.