CCl4-induced Liver Damage Research Articles

Assessment of antioxidant and hepatoprotective potential of Satureja montana extracts against CCl4 induced liver damage

The influence of Satureja montana extracts on several liver biochemical parameters in mice administered with carbon tetrachloride was estimated. In vivo investigation of antioxidant properties of S. montana extracts encompassed monitoring of biochemical parameters (derived from liver homogenate and blood hydrolyzate) and examination of potential hepatoprotective effect after intoxication with carbon tetrachloride. Biochemical tests included determination of activity of several antioxidant enzymes: xanthine oxidase, catalase, peroxidase, glutathione peroxidase, amount of reduced glutathione and intensity of lipid peroxidation. In order to obtain data about the potent hepatoprotective effect of examined extracts, the following parameters were determined: aspartate aminotrans-ferase, alanine aminotransferase, bilirubin, hepatic DNA and hydroxyprolin. Results of this study demonstrate that S. montana extracts inhibited the hepatotoxicity produced by carbon tetrachloride administration most probably through activation of physiological common defense mechanisms.

Rooibos tea (Aspalathus linearis) ameliorates the CCl4-induced injury to mitochondrial respiratory function and energy production in rat liver.

The rooibos tea (RT) is a source of valuable dietary dihydrochalcones  aspalathin, and nothofagin and other polyphenols. Many in vitro and in vivo studies have shown that RT flavonoids have strong antioxidant effect and significantly reduce oxidative stress. We investigated the antioxidant activity and protective effect of an aqueous extract of RT on the liver mitochondria oxidative phosphorylation in rats with carbon tetrachloride-induced (CCl4-induced) liver damage. Mitochondrial respiration and ATP production was determined amperometrically using a Clark-type oxygen electrode. We found significantly decreased parameters of oxidative phosphorylation in the group having received CCl4 for 10 weeks. Simultaneous administration of RT increased oxygen uptake stimulated with ADP, and the rate of ATP generation in the mitochondria of rats, both having been impaired in rats treated with CCl4 only. Treatment with RT significantly decreased CCl4-induced elevated enzyme levels, improved capacity of the respiratory chain and energy production, presumably due to its potent and direct antioxidant activity, including inhibition of mitochondrial lipid peroxidation. Improved histological features support the view of antioxidant and membrane-stabilizing activity of RT. This fact may play a significant role in the protection of the liver from injury caused by known toxins, and from subsequent development of steatosis and fibrosis..

The potential protective effect of two actinomycete extracts against carbon tetrachloride-induced hepatotoxicity in rats.

The aim of this study was to investigate the potential protective effect of two extracts derived from two soil actinomycete strains, designated S19 and G30, against CCl4-induced hepatotoxicity in male rats. Sixty-four male rats were divided into four groups of 16 rats per group. The first group was a control group given corn oil and the nutritive medium which is composed of a mixture of the two used media. The second group received CCl4 only, the third group was administered CCl4 and the extract S19, and the fourth group was administered CCl4 and the extract G30. The results were taken after a treatment period of 8weeks. Our data demonstrated that the two actinomycete extracts significantly (P < 0.01) lowered the CCl4-induced elevation of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) after 8weeks of treatment. The extract S19 had no effect on serum lactate dehydrogenase (LDH) and total bilirubin, whereas the extract G30 significantly decreased (P < 0.01) the elevated levels of these parameters in the serum, especially after 4weeks of treatment. The levels of hepatic glutathione (GSH), glutathione peroxidase (GSH-Px), peroxidase (Px), catalase (CAT), and superoxide dismutase (SOD) significantly increased (P < 0.01), while those of malondialdehyde (MDA) markedly decreased in rats treated with the two extracts. Furthermore, histopathological lesions in the liver, including necrosis, inflammatory cell infiltration, hydropic degeneration, and congestion of the central vein, were partially reversed by treatment with the two microbial extracts. Our results provided evidence for the protective effect of the two used actinomycete extracts against CCl4-induced liver damage occurred through the reduction of oxidative stress and improvement of antioxidant defense markers.

Hepatoprotective potentials of methanol extract of T. conophorum seeds of carbon tetrachloride induced liver damage in Wistar rats

BackgroundTetracarpidium conophorum (TC) is a tropical plant used in ethno medicine for treating various diseases including hepatic ailments. The present study investigated the effect of methanol extract of T. conophorum seeds in rats intoxicated with CCl4 24 h and 48 h after intoxication respectively.MethodsThirty-five male Wistar rats were distributed equally into seven groups. Group IA (control) received distilled water and olive oil (i.p), group IIA rats were intoxicated with CCl4 in olive oil (600 mg/kg, i.p.) only on the 8th day, while groups IIIA, IVA and VA were given 100 mg/kg of sylimarin, 250 mg/kg and 500 mg/kg of methanol extract respectively for 7 days, thereafter they were intoxicated with CCl4 on the 8th day. Groups VIA and VIIA were intoxicated with CCl4 on the 8th day and administered 250 mg/kg and 500 mg/kg of methanol extract of T. conophorum seeds at 1 h, 6 h, 12 h, 18 h and 24 h and the animals were sacrificed 24 h after intoxication with CCl4.This procedure was repeated for a different set of thirty-five (groups IB-VIIB) male rats but the animals were sacrificed 48 h after intoxication with CCl4. Fasting blood sample was collected by cardiac puncture for biochemical analyses.ResultsThere were significant increases (p˂0.05) in serum hepatic enzyme markers (ALT, AST, ALP, and γ-GT) activities, as well as bilirubin and significant reduction in antioxidant enzymes (P˂0.05) in rats intoxicated with CCl4 when compared to control group, but administration (pre-treatment and post-treatment) of methanol extract of T. conophorum seeds at doses of 250 and 500 mg/kg body weight and standard sylimarin drug attenuated the toxic insult of CCl4 in a dose-dependent manner at 24 h and 48 h after intoxication respectively.ConclusionsOur findings confirm that methanol extract of TC exhibited hepatoprotective activity against CCl4 induced liver damage.

Secondary Metabolites and Hepatoprotective Activity of Euphorbia retusa

Objectives: This study aimed to explore the secondary metabolites from the methanolic extract of Euphorbia retusa forssk, as it is known for its use in folk medicine and for being rich in bioactive molecules. Methods: The methanolic extractwas fractionated by different chromatographic techniques and the structures of the isolated compounds were elucidated by UV, 1H and 13C NMR spectroscopy. Hepatoprotective activity of E. retusa extract was evaluated on CCl4-induced liver damage in rats through biochemical assessment of serum ALT as well as MDA, GSH and NO. It was also evaluated through histopathological study of liver autopsy samples. Results: From the aqueous methanolic extract of Euphorbia retusa forssk. aerial parts seven known phenolic compounds; kamferol-3-O-β-D- glucopyranoside (1), quercetin -3-O-β-D- glucopyranoside (2), 3,3`dimethoxy ellagic acid (3), ellagic acid (4), gallic acid (5), kamferol (6) and quercetin (7) were isolated and identified by chromatographic and spectroscopic analysis. Administration of the extract (100 and 200 mg/kg body weight) significantly decreased the AST and ALT levels, inhibited the CCl4 -induced elevated levels of NO and MDA and increased the level of hepatic GSH. A comparative histopathological study of liver exhibited almost nearly normal architecture as compared to toxicant group. Conclusion: Euphorbia retusaextract has shown to have hepatoprotective activityon CCl4-induced liver damage in rats which might be attributed to its phenolic contents.

EFFECT OF ETHANOL STEM BARK EXTRACT OF BERLINIA GRANDIFLORA HUTCH AND DALZ ON MARKER LIVER ENZYMES IN RATS TREATED WITH CCl4

Objective: The objective of this work was to validate the traditional claim of the use of the stem bark of Berlinia grandiflora in treating liver problems by investigating the effect of its ethanol stem bark extract on maker liver enzymes in vivo.Methods: Groups of Wistar albino rats (6 in each group) were daily treated with CCl4 (2 ml/kg b.w., diluted with olive oil 1:1 v/v, intravenously), followed by oral administration of ethanol stem bark extract of Berlinia grandiflora (ESBG) at doses 100, 300 and 900 mg/kg b.w. respectively, 3 h after the administration of the CCl4. Serum biochemical parameters were measured 24 h at the end of the 7-day treatment period and compared to a group intoxicated with CCl4 (2 ml/kg b.w., diluted with olive oil 1:1 v/v, intravenously) alone.Results: Treatment of rats with ESBG (at doses 100, 300 and 900 mg/kg b.w. orally) reduced the impact of CCl4-induced hepatotoxicity on liver maker enzymes Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and total bilirubin (TB), with the 900 mg/kg b.w. showing a significant reduction (p&lt;0.05) compared to the group intoxicated with CCl4. The extract reversed the impact of the CCl4-induced hepatotoxicity by increasing the concentration of the serum Total protein (TP) and albumin (ALB), with the 900 mg/kg b.w. dose showing a significant increment (p&lt;0.05) compared to the group intoxicated with the CCl4.Conclusion: The investigation of the effect of Berlinia grandiflora on CCl4 induced liver damage revealed that the ethanol extract of the stem bark of the plant was able to reverse the hepatotoxicity, with the 900 mg/kg b.w. dose showing a significant activity.

In vivo Hepatoprotective and Antioxidant Activity of Enicostemma littorale against Ccl4 Induced Liver Damage in Rats

In vivo Hepatoprotective and Antioxidant Activity of Enicostemma littorale against Ccl4 Induced Liver Damage in Rats

AAV serotype 8-mediated liver specific GNMT expression delays progression of hepatocellular carcinoma and prevents carbon tetrachloride-induced liver damage

Glycine N-methyltransferase (GNMT) is abundantly expressed in normal livers and plays a protective role against tumor formation. GNMT depletion leads to progression of hepatocellular carcinoma (HCC). In this study, we investigated the activity of ectopic GNMT delivered using recombinant adeno-associated virus (AAV) gene therapy in mouse models of liver cirrhosis and HCC. Injection of AAV serotype 8 (AAV8) vector carrying the GNMT gene (AAV8-GNMT) in Gnmt−/− mice increased GNMT expression and downregulated pro-inflammatory responses, resulting in reduced liver damage and incidence of liver tumors. Moreover, AAV8-GNMT resulted in the amelioration of carbon tetrachloride (CCl4)-induced liver fibrosis in BALB/c mice. We showed that AAV8-GNMT protected hepatocytes from CCl4-induced liver damage. AAV8-GNMT significantly attenuated the levels of pro-fibrotic markers and increased efficiency of hepatocyte proliferation. These results suggest that correction of hepatic GNMT by gene therapy of AAV8-mediated gene enhancement may provide a potential strategy for preventing and delaying development of liver diseases.

Andrographolide derivative as STAT3 inhibitor that protects acute liver damage in mice

Sustained activation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway contributed to the progression of cancer and liver diseases. STAT3 signaling inhibitor has been extensively investigated for pharmacological use. We synthesized a series of andrographolide derivatives, and characterized their activity against STAT3 signaling pathway both in vitro and in the CCl4-induced acute liver damage mice model. Among these derivatives, compound 24 effectively inhibited phosphorylation and dimerization of STAT3 but not its DNA binding activity. Compound 24 significantly ameliorated carbon tetrachloride-induced acute liver damage in vivo without changing mice body weight. Treatment with 24 attenuated hepatic pathologic damage and promoted hepatic proliferation and activation of STAT3. Compound 24 inhibited elevated expression of α-smooth muscle actin and serum pro-inflammatory cytokines downstream of STAT3 but not those factors that are regulated by NF-κB or SMADs. In summary, our results suggest that compound 24 may serve as a potential therapeutic agent for the treatment of hepatic damage or a liver protection agent via regulating STAT3 activation.

IN VITRO ANTIOXIDANT POTENTIAL AND HEPATOPROTECTIVE ACTIVITY OF TAXUS WALLICHIANA

Objectives: Taxus wallichiana, the member of family Taxaceae is used for the cure of various ailments by a large ethnic population native to the forests in Kashmir valley. The aim of this study is to evaluate antioxidant potential and hepatoprotective action of T. wallichiana as claimed by the ethnic population segment. Methods: Antioxidant potential of different T. wallichiana extracts was evaluated by estimating the total phenolics, 1,1-diphenyl -2-picrylhydrazyl (DPPH), reducing power, microsomal lipid peroxidation (LPO), and hydroxyl radical scavenging activity through standard protocols. Hepatoprotective activity of T. wallichiana was determined by evaluation of liver marker enzyme (aspartate transaminase, alanine transaminase, and alkaline phosphatase) levels using standard protocols and by histological analysis of rat liver tissues of different animal groups against CCl4 induced liver damage. Results: Phenolic content expressed as gallic acid equivalents (GAE/g) was found maximum in case of ethanolic extract (153.34 mg GAE/g), followed by extracts of methanol (149.24 mg GAE/g), hexane (134 mg GAE/g), ethyl acetate (128.9 mg GAE/g), chloroform (121.37 mg GAE/g), and aqueous (113.00 mg GAE/g). At concentration of 700 μg/ml, DPPH radical scavenging activity of methanol extract was 88.29% with IC50 (212.00 μg/ml), aqueous (82.47%) with IC50 (258.29 μg/ml), and ethyl acetate (79.57%) with IC50 (301.80%μg/ml). The reducing power of the extracts increased in a concentration dependent manner. At concentration of 700 μg/ml, 79%, 68%, and 56% inhibition was observed with extracts of methanol, aqueous, and ethyl acetate on microsomal LPO with IC50 values of 126.09, 168.83, and151.96 μg/ml, respectively. Superoxide radical scavenging activity of T. wallichiana extracts increased in a dose-dependent manner with IC50 values 170.30 μg/ml (methanol), 257.00 μg/ml (aqueous), and 297.55 μg/ml ethyl acetate extract. T. wallichiana extracts exhibited antioxidant effects on calf thymus DNA damage. The results further depict the hepatoprotective action of T. wallichiana extract at doses of 100 and 300 mg/kg and were comparable with that of standard treatment comprising 50 mg/kg-day of Vitamin C, a known hepatoprotective agent. The data were substantiated with histopathological studies of rat liver sections. Conclusion: These results comprehensively depict that T. wallichiana extracts are endowed with the free radical sequestering potential and be employed as potential antioxidant and hepatoprotective arsenal against many oxidative stress linked diseases.

Yu Gan Long reduces rat liver fibrosis by blocking TGF-β1/Smad pathway and modulating the immunity

Yu Gan Long (YGL) is a Chinese traditional herbal medicine that has been used in the treatment of liver fibrosis for many years in clinical practice. However, its anti-hepatofibrotic mechanism has not been studied yet. In this study, the effect and mechanism of YGL in reducing liver fibrosis was demonstrated in vivo. Our results showed that liver fibrosis biomarkers collagen IV (Col IV), type III precollagen (PCIII), hyaluronuc acid (HA) and laminin (LN), were increased after CCl4 treatment and decreased by YGL. Among the liver fibrosis indicators, α-smooth muscle actin (α-SMA) was decreased by YGL in the CCl4-treated rats, while MMP2 and MMP9 was upregulated followed by TIMP1 downregulation. Proteins involved in liver fibrosis such as p-Smad2, p-Smad3 and Smad4 were down-regulated, while Smad7 protein was up-regulated by YGL after CCl4-induced liver damage. YGL also suppressed the increase of TGF-β1, TNF-α, IL-1β, IL-6, IL-4 and IL-17 A induced by CCl4 treatment, while promoted IFN-γ expression. Finally, the transcription factors ROR-γt and GATA3 were decreased, while T-bet was increased after YGL treatment. These results suggested that YGL attenuated CCl4-induced hepatic fibrosis by accelerating the extracellular matrix degradation, blocking the TGF-β1/Smad signaling pathway and modulating the balance among IL-4, IL-17 A and IFN-γ, demonstrating YGL protective effect and its potential mechanisms in treating liver fibrosis.

EVALUATION OF HEPATOPROTECTIVE EFFECT OF ETHANOLIC EXTRACT FROM RED BETEL (PIPER CROCATUM RUIZ AND PAV.) LEAVES

Objective: The objective of this study is to identify the effect of red betel (Piper crocatum Ruiz and Pav.) leaves ethanolic extract on hepatoprotective effect on CCl4-induced liver damage in rats.Methods: Standard phytochemical screening method was done for preliminary phytochemical screening. Hepatotoxic rats were induced with CCl4 and treated with ethanolic extract of red betel leaves. The hepatoprotective test was divided into two groups (curative and preventive test). In the curative test, the rats which have been induced with CCl4 were given ethanol extract 600 mg/kg bw each day for 15 days. In the preventive test, the induced rats were given ethanol extract 600 mg/kg bw each day and CCl4 each 4 h for 45 days. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) parameters were also measured.Result: The phytochemical screening showed an ethanolic extract of red betel leaves which contain a lot of phytochemical compounds. The result of hepatoprotective study showed that the ALT, AST, and ALP registered a significant (p&lt;0.05) alteration in CCl4treated rats.Conclusion: The ethanolic extract of red betel leaves had the curative and preventive test.

Protective effect of polysaccharide from Agaricus bisporus in Tibet area of China against tetrachloride-induced acute liver injury in mice

In this study, we systematically investigated the physicochemical properties, hepatoprotective activities and the underlying mechanisms of Agaricus bisporus polysaccharide (FPS). The physicochemical evaluations indicate that FPS is mainly composed of glucose, mannose, galactose, fucose, arabinose and glucuronic acid with the mole percentages of 70.30%, 8.70%, 12.88%, 0.79%, 5.04% and 1.57%, respectively. The results of methylation analysis indicated that FPS mainly included 1-linked-glc, 1,4-linked-glc, 1,6-linked-glc, 1,3-linked-gal and 1,3,6-linked-man glycosidic bonds. The results from hepatoprotective studies showed that FPS significantly decreased the liver index, serum gamma-glutamyltranspeptidase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) activities and malondialdehyde (MDA) contents in liver tissue, and increased antioxidant capacities of hepatic glutathione (GSH) and superoxide dismutase (SOD). Furthermore, histological examination of liver tissues showed that FPS alleviated CCl4-induced liver injury. Finally, the Western blot results showed that FPS could significantly decrease the expression levels of TGF-β1 and Smad3 in the liver. These results together suggest that FPS possesses hepatoprotective effect against CCl4-induced liver damage, in part through the downregulation of TGF-β1/Smad signaling pathway, therefore FPS could be considered as a hepatoprotective medicine or functional food.

Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl₄-Induced Acute Liver Damage in C57BL/6 Mice.

Species of Cirsium (Asteraceae family) have been used in folk hepatoprotective medicine in Taiwan. We collected four Cirsium species—including the aerial part of Cirsium arisanense (CAH), the aerial part of Cirsium kawakamii (CKH), the flower part of Cirsium japonicum DC. var. australe (CJF), and Cirsii Herba (CH)—and then made extractions from them with 70% methanol. We compared the antioxidant contents and activities of these four Cirsium species extracts by a spectrophotometric method and high-performance liquid chromatography–photodiode array detector (HPLC-DAD). We further evaluated the hepatoprotective effects of these extracts on CCl4-induced acute liver damage in C57BL/6 mice. The present study found CAH possesses the highest antioxidant activity among the four Cirsium species, and these antioxidant activities are closely related to phenylpropanoid glycoside (PPG) contents. The extracts decreased serum ALT and AST levels elevated by injection with 0.2% CCl4. However, only CJF and CH decreased hepatic necrosis. Silibinin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic necrosis caused by CCl4. CJF and CH restored the activities of hepatic antioxidant enzymes and decreased hepatic malondialdehyde (MDA) levels. CJF further restored the expression of hepatic antioxidant enzymes including Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), and glutathione S-transferase (GST) proteins. HPLC chromatogram indicated that CKH, CJF, and CH contained silibinin diastereomers (α and β). Only CJF contained diosmetin. Hence, the hepatoprotective mechanism of CJF against CCl4-induced acute liver damage might be involved in restoring the activities and protein expression of the hepatic antioxidant defense system and inhibiting hepatic inflammation, and these hepatoprotective effects are related to the contents of silibinin diastereomers and diosmetin.

Caffeic acid rich Citrus macroptera peel powder supplementation prevented oxidative stress, fibrosis and hepatic damage in CCl4 treated rats

BackgroundCitrus macroptera has been used as a culinary fruit and medicinal plant in traditional medicine system in Bangladesh. The aim of the present study was to evaluate the presence of phenolic compounds in Citrus macroptera peel powder and the protective effect of Citrus macroptera against carbon tetrachloride (CCl4)-induced liver injury in rats.MethodsThe hepatoprotective activity was assessed using various biochemical parameters such as liver marker enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)) and oxidative stress parameters. Histopathological changes in the liver of different groups were also studied.ResultsAdministration of CCl4 increased the serum ALT, AST, ALP enzymatic activities and lipid peroxidation products but decreased the cellular antioxidant activities and reduced glutathione (GSH) levels in rats which were brought back to near normal levels by the treatment with Citrus macroptera. Citrus macroptera administration has also shown to decrease the necrotic zones, fibrosis and inflammatory cell infiltration in CCl4 treated rats. HPLC-DAD analysis of Citrus macroptera extract showed the great presence of caffeic acid and (−) epicatechin.ConclusionThe results of this study suggest that Citrus macroptera exerts hepatoprotective activity via promoting the antioxidant defense against CCl4-induced oxidative liver damage.

Characterization, antioxidant activity and hepatoprotective effect of purple sweetpotato polysaccharides

In this study, three kinds of polysaccharides (named PSWP, PSAP-1 and PSAP-2) were successively isolated from purple sweetpotato tubers by hot water, 0.5M and 2M sodium hydroxide solutions. The characterization, in vitro antioxidant activity and in vivo hepatoprotective effect of these polysaccharides were investigated. Results indicated that PSWP, PSAP-1 and PSAP-2 were all β-type polysaccharides containing different contents of uronic acid, protein and polyphenol. Both PSWP and PSAP-1 were composed by arabinose, glucose and galactose, whereas PSAP-2 was consisted of arabinose, rhamnose and glucose. All the polysaccharides exhibited moderate 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and reducing power. As compared with tetrachloromethane (CCl4) treatment group, mice administrated with PSWP, PSAP-1 and PSAP-2 exhibited decreased levels of serum enzymes (alkaline phosphatase, alanine transaminase and aspartate transaminase) and hepatic lipid peroxidation, whereas increased levels of hepatic antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic antioxidant (glutathione). Notably, PSWP displayed stronger antioxidant activity and hepatoprotective effect than PSAP-1 and PSAP-2. The hepatoprotective effect of PSWP was comparable to positive standard of silymarin. Our results suggested polysaccharides from purple sweetpotato possessed potential antioxidant activity and protective effect against CCl4-induced acute liver damage.

Pre- vs. post-treatment with melatonin in CCl4-induced liver damage: Oxidative stress inferred from biochemical and pathohistological studies

AimsThe present study was designed to compare the ameliorating potential of pre- and post-treatments with melatonin, a potent natural antioxidant, in the carbon tetrachloride-induced rat liver damage model by tracking changes in enzymatic and non-enzymatic liver tissue defense parameters, as well as in the occurring pathohistological changes. Main methodsRats from two experimental groups were treated with melatonin before and after CCl4 administration, while the controls, negative and positive, received vehicle/melatonin and CCl4, respectively. Serum levels of transaminases, alkaline phosphates, γ-GT, bilirubin, and albumin, as well as a wide panel of oxidative stress-related parameters in liver tissue, were determined in all experimental animals. Liver tissue specimens were stained with hematoxylin and eosin and further evaluated for morphological changes. Key findingsBoth pre- and post-treatment with melatonin prevented a CCl4-induced increase in serum (ALT, AST, and γ-GT) and tissue (MDA and XO) liver damage markers and a decrease in the tissue total antioxidant capacity, in both enzymatic and non-enzymatic systems. The intensity of pathological changes, hepatocyte vacuolar degeneration, necrosis and inflammatory cell infiltration, was suppressed by the treatment with melatonin. SignificanceIn conclusion, melatonin, especially as a post-intoxication treatment, attenuated CCl4-induced liver oxidative damage, increased liver antioxidant capacities and improved liver microscopic appearance. The results are of interest due to the great protective potential of melatonin that was even demonstrated to be stronger if applied after the tissue damage.

Protective effect of the total flavonoids from Apocynum venetum L. on carbon tetrachloride-induced hepatotoxicity in vitro and in vivo

Apocynum venetum L., belonging to the family Apocynaceae, is a popular medicinal plant, which is commonly used in the treatment of hypertension, neurasthenia, and hepatitis in China. In the present study, the total flavonoids (TFs) were prepared from the leaves of A. venetum, and its protective effects on carbon tetrachloride (CCl4)-induced hepatotoxicity in a cultured HepG2 cell line and in mice were investigated. Cell exposed to 0.4% CCl4 (v/v) for 6h led to a significant decrease in cell viability, increased LDH leakage, and intracellular reactive oxygen species (ROS). CCl4 also induced cell marked apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP). Pretreatment with TFs at concentrations of 25, 50, and 100μg/mL effectively relieved CCl4-induced cellular damage in a dose-dependent manner. In vivo, TFs (100, 200, and 400mg/kg BW) were administered via gavage daily for 14days before CCl4 treatment. The high serum ALT and AST levels induced by CCl4 were dose-dependently suppressed by pretreatment of TFs (200 and 400mg/kg BW). Histological analysis also supported the results obtained from serum assays. Furthermore, TFs could prevent CCl4-caused oxidative damage by decreasing the MDA formation and increasing antioxidant enzymes (CAT, SOD, GSH-Px) activities in liver tissues. In summary, both in vitro and in vivo data suggest that TFs, prepared from A. venetum, showed a remarkable hepatoprotective and antioxidant activity against CCl4-induced liver damage.

Cordyceps cicadae NTTU 868 mycelium prevents CCl4-induced hepatic fibrosis in BALB/c mice via inhibiting the expression of pro-inflammatory and pro-fibrotic cytokines

Hepatic fibrosis is caused by chronic liver injury and repeated repair with scar tissue accumulation in the liver. Cordyceps cicadae produces large quantities of adenosine, N6-(2-hydroxyethyl)-adenosine (HEA) and polysaccharides. This study investigated the effect of C. cicadae NTTU 868 mycelium and its bioactive compounds on carbon tetrachloride (CCl4)-induced liver fibrosis. BALB/c mice were injected 0.5 µL/g CCl4 3 times weekly for 4 weeks to induce hepatic fibrosis and treated with C. cicadae NTTU 868 mycelium, adenosine, HEA, and polysaccharides daily for 6 weeks. CCl4 administration not only caused a remarkable liver damage but also resulted in abnormal collagen accumulation. C. cicadae NTTU 868 mycelium prevented CCl4-induced hepatic fibrosis through TNF-α/IL-6 pathway, TGF-β1/CTGF pathway, and anti-oxidative defense mechanism. Although adenosine, HEA and polysaccharides performed protection against CCl4-induced liver damage, HEA should be the main bioactive compound on the prevention of hepatic fibrosis in the C. cicadae NTTU 868 mycelium.

Hepatoprotective effect of methanol fruit pulp extract of Musa paradisiaca on carbon tetrachloride-induced liver toxicity in Wistar rats

CONTEXT: Musa paradisiaca (Banana) fruit pulp has been used in folk medicine to treat various kinds of ailments, such as dysentery, diarrhea, bronchitis, ulcer, fevers, and hemorrhages in different parts of the globe, including Nigeria, Western Africa. AIM: This study was designed to histologically and biochemically assess the protective effect of methanol fruit pulp extract of M. paradisiaca (MFMP) on carbon tetrachloride (CCl4)-induced hepatotoxicity in Wistar rats. MATERIALS AND METHODS: Twenty-four Wistar rats were divided into six groups (I–VI; n = 4). Group I (control) was administered distilled H2O (2 ml/kg), whereas Groups II, III, and IV were administered MFMP (500 mg/kg, 1000 mg/kg, and 1500 mg/kg, respectively) and Group V administered Silymarin (100 mg/kg), as the reference drug, for a period of 14 days. Hepatotoxicity was induced in rats by the administration of CCl4(1 ml, 1:1 solution: olive oil). On the 15th day, Groups II–VI were administered single dose of CCl4. All administrations were through the oral route. After 12 h of CCl4administration, rats were euthanized and liver organs harvested for routine (H and E) histological tissue processing and blood samples collected for biochemical analysis of serum liver enzymes (alanine transaminase, aspartate transaminase, and alkaline phosphatase). RESULTS: MFMP-treatment revealed remarkable histoarchitectural preservation of the liver parenchyma against CCl4-induced liver damage and decreased (P CONCLUSION: Result suggests that MFMP possesses hepatoprotective potentials against chemically-induced acute hepatotoxicity in Wistar rats. Hepatoprotective potential of MFMP is possible as a result of its antioxidant properties.