CCl4-induced Liver Damage Research Articles

Hepatoprotective effect against CCl4-induced acute liver damage in mice and High-performance liquid chromatography mass spectrometric method for analysis of the constituents of extract of Rubus crataegifolius

This study is an attempt to evaluate the hepatoprotective activity of Rubus Crataegifolius against carbon tetrachloride-induced liver injury in mice. 70% ethanolic, ethyl acetate and n-BuOH extract of R. crataegifolius were administered daily for 14 days in experimental animals before they were treated with CCl4. The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin. A high-performance liquid chromatography mass spectrometric (HPLC-EIS-MS/MS) method was developed for the determination of the constituents of the extracts. According to the data of HPLC-EIS-MS/MS, the chemical structures of the largely 14 constituents of R. crataegifolius were identified online without time-consuming isolation. Ethyl acetate extracts of R. crataegifolius showed strong antioxidant activities and significant protective effect against acute hepatotoxicity induced by CCl4. According to the data of HPLC-EIS-MS/MS, Oleanic acid, Phlorizin dehydrate and Quercetin-3-rhamnoside are considered as the main hepatoprotective factor in ethyl acetate extract.

In vivo Pharmacological Effectiveness of Heat-treated Cucumber (Cucumis sativus L.) Juice against CCI4- induced Detoxification in a Rat Model

Abstract: Background: Detoxification of heavy metals such as carbon tetrachloride (CCl4) poisoning has become a major focus of researchers. Objectives: In this study, heat-treated cucumber juice was assessed for its pharmacological effect on protection of carbon tetrachloride (CCl4)-induced acute liver and kidney damages. Methods: Initially, during detoxification of CCl4, the rats of all groups except the control group (without treatment) were injected with a single intraperitoneal dose of 2.5 mL CCl4/kg with 50% concentration (1:1 ratio; v/v in olive oil). Additionally, CCl4-treated rats were also dosed with saline, 10 mg/kg, 100 mg/kg, and 500 mg/kg cucumber juice for 1, 3 and 5 days once in a day after 6 h from CCl4 administration. Results: As a result, the best concentration of cucumber juice was noted to be 10 mg/kg, which showed remarkable protective effect on body weight (212-217 g), enzymatic activities of aspartate aminotransferase (AST; 53 IU/L), alanine aminotransferase (ALT; 125 IU/L), blood urea nitrogen (BUN; 18.8 mg/dL), and creatinine content (0.65 mg/dL) as compared to control (220-232 g; 477 IU/L; 987 IU/L; 16.8 mg/dL; and 0.95 mg/dL), respectively. Moreover, histology and histomorphometry analysis of liver and kidney led to significant reduction in percentage of hepatopathy and nephropathy parameters such as hepatic (46.90±2.63%) and kidney (39.86±2.01) degenerative regions, number of hepatocytes (638.00±47.25), tubules (327.60±26.67) and glomerulus (29.20±1.36). Conclusion: These findings suggest that heat-treated cucumber juice has a significant pharmacological effect on CCl4-induced acute liver and kidney damages in experimental rats. Key words: Cucumis sativus, Cucumber juice, CCl4 detoxification, AST, ALT, BUN.

Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling.

Chrysin (5,7-dihydroxyflavone) is a naturally occurring flavonoid present at high levels in honey, propolis and numerous plant extracts. Chrysin is known to have hepatoprotective activity, however, the mechanisms by which it exerts this effect remain unclear. In the present study, the effects of chrysin in carbon tetrachloride (CCl4)-induced acute liver damage were investigated and the results used to infer a possible mechanism behind chrysin's hepatoprotective activity. Prior to an intraperitoneal injection of CCl4 (1 ml/kg) to induce acute liver damage, chrysin (50 mg/kg) was administered orally to mice for 7 days. The positive control group was given 50 mg/kg standardized silymarin, a well-studied hepatoprotective flavonoid. Twenty-four h following CCl4 administration, an increase in the activity levels of serum aspartate-amino-transferase and alanine-amino-transferase was found. This was accompanied by extended centrilobular necrosis, steatosis and an altered hepatocyte ultrastructure. In addition, CCl4-induced acute hepatotoxicity was associated with an increase in hepatic tumor necrosis factor-α (TNF-α) and α-smooth muscle actin (α-SMA) protein expression, which was significantly decreased in the livers of mice pre-treated with chrysin (P<0.001), similar to the results of the silymarin pre-treated group (P<0.001). Treatment with chrysin prior to CCl4 exposure significantly reduced the activity of enzymes used as biochemical markers of poor liver function compared with the group which did not receive pre-treatment (P<0.001). In addition, the results of histopathological and electron microscopy liver examination showed chrysin pre-treatment reduced the effects of CCl4 treatment. Molecular modeling results demonstrated that the hepatoprotective activity of chrysin is mediated through TNF-α, as it reduces soluble TNF-α generation via blocking TNF-α-converting enzyme activity. In conclusion, the results of the present study suggest that inflammatory pathways are activated in CCl4-induced acute liver damage, which are ameliorated by chrysin pre-treatment. This indicates that chrysin is a potent hepatoprotective agent, similarly to silymarin at the same dose, which has the potential to be a viable alternative to conventional hepatoprotective treatments.

Protective effect of a polysaccharide from Anoectochilus roxburghii against carbon tetrachloride-induced acute liver injury in mice

Ethnopharmacological relevanceAnoectochilus roxburghii (Wall.) Lindl. is traditionally used for the treatment of various types of chronic and acute hepatitis in China. Considering that Anoectochilus roxburghii polysaccharide (ARPT) is the main constituent of Anoectochilus roxburghii, the present study was designed to investigate the hepatoprotective effect of ARPT and its possible mechanism in carbon tetrachloride (CCl4)-induced mice. Material and methodsThe hepatoprotective activity of ARPT (150, 300 and 500mg/kg) were investigated on CCl4-induced acute liver damage in mice. The activities of alanine transaminase (ALT), aspartate transaminase (AST) were determined in serum. The hepatic levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured in liver homogenates. The levels of cytochrome P450 sub family 2E1 (CYP2E1), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), KC (Murine IL-8 ortholog), transforming growth factor-beta1 (TGF-β1), Bcl-2 and Bax were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The expressions of CYP2E1, nuclear factor-kappa B (NF-κB) p65 and caspase-3 were evaluated by western blot assays. The hepatic levels of TNF-α, IL-6, MIP-2 and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, histopathological observation and terminal-deoxynucleoitidyl transferase mediated nick end labeling assay (TUNEL) were carried out on the separated livers of mice. ResultsARPT significantly decreased serum ALT and AST activities, hepatic MDA level, and markedly enhanced antioxidant enzyme (SOD, CAT and GSH-Px) activities and GSH level in hepatic tissue, in a dose-dependent manner, when compared to the model group. Histopathological observation revealed the hepatoprotective effect of ARPT against the damage. Furthermore, ARPT remarkably inhibited CYP2E1 mRNA expression, decreased NF-κB p65 expression and therefore to prevent the secretion of pro-inflammatory cytokines (TNF-α and IL-6) and chemokines (MCP-1, MIP-2 and KC), suppressed TGF-β1 expression and hepatocytes apoptosis. Moreover, ARPT could prevent DNA fragmentation based on TUNEL assay results. ConclusionThese findings suggested that ARPT possessed hepatoprotective effect against CCl4-induced hepatotoxicity in mice and the action might in part be through reducing oxidative stress, inflammation and apoptosis.

Hepatoprotective Studies of Methanolic Leaf Extract of Barringtonia acutangula (L) against Carbon Tetrachloride Induced Liver Injury in Wistar Rats

Physiological activities of liver result in the generation of highly reactive free radicals and various biochemical reactions make liver cells prone to attack and necrosis also excessive release of reactive oxygen species results in the organ damage. Herbal drugs plays important role as antioxidant in the management of various liver disorders which can even speed up the natural healing processes of the liver. Barringtonia acutangula L. an evergreen tree of moderate size was used in various indigenous systems of medicine against several diseases and almost every part of the plant has diverse pharmacological properties. The hepatoprotective property of this plant extracts was analyzed in this study in which leaf extracts were obtained using methanol further phytochemical and antioxidant properties were analyzed. In vivo studies were carried out for hepatoprotective studies on CCl4 induced liver damage following histopathological studies of rat liver tissues to support the induction of hepatoprotective efficacy. The grouping of animals consists of 6 rats per group in which group I has CCl4 induced rats treated with Silymarin (100 mg/kg b.w) for 30 days, group II & III has CCl4 induced rats treated with methanolic extract of Barringtonia acutangula (250 mg/kg b.w) & (500 mg/kg b.w) for 30 days. Biochemical analysis reveals that the values of parameters of treated groups have become too normal compared to the control group. Histopathology results suggest that there is improvement in the cell counts and decrease in vacuoles. Therefore, results of in vivo and in vitro studies indicate that has more potential at 500 mg/kg b.w concentration.

Hepatoprotective effect of methanolic Tanacetum parthenium extract on CCl4-induced liver damage in rats.

The purpose of this study was to investigate the effects of Tanacetum Parthenium Extract (TPE) on Lipid peroxidation, antioxidant enzymes, biochemical factors, and liver enzymes in the rats damaged by Carbon Tetrachloride (CCl4). 54 male Wistar rats were divided into 9 groups each consisting of 6 rats. Two of the groups were control groups (normal and damage control groups), 4 of them were exposure groups which were respectively administered with 40, 80, and 120mg/kg of TPE and silymarin for 14days before being damaged by CCl4, and the other 3 groups were post-treatment groups which received 80 and 120mg/kg of TPE and silymarin 2, 6, 24, and 48h after being injected with CCl4. At the end of the study, biochemical factors, serum liver enzymes, malondialdehyde level, antioxidant enzymes, and liver morphology were assayed. Pre- and post-treatment with TPE could significantly decrease ALT, AST, ALP, TG, LDL, TC, and glucose levels and increase HDL, and albumin levels and catalase, SOD, and GPx activities compared to the CCl4-damaged control group. The results of this study are indicative of the antioxidant activity of TPE, its potential hepatoprotective effects, and its probable therapeutic properties for laboratory animals damaged by CCl4.

Polygonum amplexicaule Extract: An Effective Herbal Cure to CCl4 Induced Liver Damage In Vivo

Introduction: Liver damages are mainly caused by toxic chemicals, alcohol, infections and autoimmune disorders. Polygonum amplexicaule is a member of the genus Polygonum having high antioxidant contents and it has traditional medicinal attributes in treatment of many ailments particularly liver damage. Objectives: Keeping in view the medicinal importance of P. amplexicaule, present study was constructed for in-vivo hepatoprotective activity of its rhizome extract in albino mice. Methods: BALB/C albino mice were selected for experimental assays and sorted in nine groups (group i-iii control groups, group iv-ix herb treated groups) with six mice in each group for six days treatment. Blood samples from anesthetized mice (20% chloroform) were collected by carotid artery puncture allowed to coagulate at room temperature for 30 min and then centrifuged at 3000 rpm for 8-10 min. The serum separated was preserved at -20°C for subsequent analysis of biochemical parameters. Animals were sacrificed under diethyl ether anaesthesia at fasting state, liver tissues were quickly excised and were stored in fixative sera (10% formalin), for histology. Results: Results revealed that CCl4 had significantly reduced the body weight and increased the level of ALT, AST, ALP and plasma bilirubin compared to toxic control. The pre-treatment of CCl4-administrated mice with extracts of P. amplexicaule at concentration of 200 mg/kg induced a profound decrease (62-94.4%) in the elevated activities of ALT, AST, ALP and plasma bilirubin level. Conclusion: P. amplexicaule extracts have hepatoprotective activity and it can be used as herbal medicine for use in food, medicines and healthcare products to cure liver damages.

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.

Protective effect of Anoectochilus roxburghii polysaccharide against CCl4-induced oxidative liver damage in mice

This study investigated the isolation and characterization of Anoectochilus roxburghii polysaccharides (ARP), and further evaluated whether ARP possessed hepatoprotective activities against CCl4-induced oxidative liver damage in mice. ARP is comprised of glucose and galactose in a 1.9:1 molar ratio, and the molecular weight is 19.5kDa. ARP displayed significant scavenging effects against hydroxyl radical, superoxide anion radical, DPPH radical and a strong reducing power. In vivo experiment demonstrated ARP (150mg/kg) administrated to mice for 7days prior to carbon tetrachloride treatment, attenuated the elevated expression levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG) in serum and inhibited the formation of hepatic malondialdehyde (MDA). ARP pretreatment also increased antioxidant enzyme activities such as glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) in the liver of CCl4-induced mice. Furthermore, hepatic histopathological changes induced by CCl4 were significantly normalized by ARP pretreatment. These findings demonstrated that ARP possessed hepatoprotective effect against acute CCl4-induced liver damage by reducing lipid oxidation.

Dicranostiga leptopodu (Maxim.) Fedde extracts attenuated CCl4-induced acute liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function

Dicranostiga Leptodu (Maxim.) fedde (DLF), a poppy plant, has been reported have many benefits and medicinal properties, including free radicals scavenging and detoxifying. However, the protective effect of DLF extracts against carbon tetrachloride (CCl4)-induced damage in mice liver has not been elucidated. Here, we demonstrated that DLF extracts attenuated CCl4-induced liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function. In this study, the mice liver damage evoked by CCl4 was marked by morphology changes, significant rise in lipid peroxidation, as well as alterations of mitochondrial respiratory function. Interestingly, pretreatment with DLF extracts attenuated CCl4-induced morphological damage and increasing of lipid peroxidation in mice liver. Additionally, DLF extracts improved mitochondrial function by preventing the disruption of respiratory chain and suppression of mitochondrial Na+K+-ATPase and Ca2+-ATPase activity. Furthermore, administration with DLF extracts elevated superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels and maintained the balance of redox status. This results showed that toxic protection effect of DLF extracts on mice liver is mediated by improving mitochondrial respiratory function and keeping the balance of redox status, which suggesting that DLF extracts could be used as potential toxic protection agent for the liver against hepatotoxic agent.

Effect of Careya arborea Roxb. on CCl4 induced liver damage in rats

Effect of Careya arborea Roxb. on CCl4 induced liver damage in rats

Inulin-type fructan and infusion of Artemisia vulgaris protect the liver against carbon tetrachloride-induced liver injury

BackgroundInfusions of aerial parts of Artemisia vulgaris L. (Asteraceae) are used in herbal medicine to treat several disorders, including hepatosis. PurposeEvaluation of in vivo hepatoprotective effects of A. vulgaris infusion (VI) and inulin (VPI; i.e., the major polysaccharide of VI). Study designThe hepatoprotective effect of A. vulgaris extracts on carbon tetrachloride (CCl4)-induced hepatotoxicity and the probable mechanism involved in this protection were investigated in mice. MethodsA. vulgaris infusion (VI) was prepared according to folk medicine using the aerial parts of the plant. Carbohydrate, protein, and total phenolic content was determined in VI, and its phenolic profile was determined by high-performance liquid chromatography (HPLC). Male Swiss mice were orally pretreated for 7 days with VI or VPI (once per day). On days 6 and 7 of treatment, the mice were intraperitoneally challenged with CCl4. Liver and blood were collected and markers of hepatic damage in plasma and oxidative stress in the liver were analyzed. Hepatic histology and inflammatory parameters were also studied in the liver. The scavenging activity of VI and VPI were evaluated in vitro using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. ResultsVI contained 40% carbohydrates, 2.9% proteins and 9.8% phenolic compounds. The HPLC fingerprint analysis of VI revealed chlorogenic, caffeic and dicaffeoylquinic acids as major low-molar-mass constituents. Oral pretreatment with VI and VPI significantly attenuated CCl4-induced liver damage, reduced the activity of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in plasma, and prevented reactive oxygen species accumulation and lipid peroxidation in the liver. Comparisons with the CCl4-treated group showed that VI and VPI completely prevented necrosis, increased the levels of reduced glutathione (GSH), and reduced tumor necrosis factor alpha (TNF-α) level in the liver. VI and VPI also exhibited high radical scavenging activity in vitro. ConclusionVI and VPI had remarkable hepatoprotective effects in vivo, which were likely attributable to antioxidant and immunomodulatory properties. The present findings support the traditional use of A. vulgaris infusion for the treatment of hepatic disorders.

The hepatoprotective activity of olive oil and Nigella sativa oil against CCl4 induced hepatotoxicity in male rats.

BackgroundLiver disease is the major cause of serious health problem leading to morbidity and mortality worldwide and the problem has increased in search for hepatotherapeutic agents from plants. The present study was designed to compare the probable hepatoprotective activity of olive oil and N. sativa oil on CCl4 induced liver damage in male rats.MethodsForty males of a new model of albino rats (Wistar strain) (175–205 g) were divided into four groups. The 1st Group (G1) was the negative control group, the remaining rats were injected with CCl4 (1 ml/kg body weight) with equal amount of olive oil on the 1st and 4th day of every week for 4 weeks. The 2nd group (G2) was the positive control, the 3rd group (G3) and the fourth group (G4) were treated orally with N. sativa oil and olive oils using stomach tube.ResultsThe positive control group showed an increase in hepatic enzymes, total bilirubin, creatinine, uric acid, lipid peroxide total cholesterol, triglyceride, low density lipoprotein, very low density lipoproteins, interleukin-6, and a decrease in antioxidant enzymes, high density lipoprotein cholesterol, a decrease in total protein and albumin an when compared with negative control group. Histology of the CCl4 treated group revealed inflammation and damage of liver cells. Treating the hepatotoxic rats with olive oil and N. sativa oil showed a significant improvement in all biochemical tests compared with the positive CCl4 control group. In addition, the liver tissues of olive oil treated group showed mild improvement in inflammatory infiltration and in N. sativa oil treated group showed normal hepatocytes with no evidence of inflammation.ConclusionThis study revealed that olive oil and N. sativa oil have a protective effect against CCl4-induced hepatotoxicity in male rats. Nigella sativa oil was more effective than olive oil.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases necroinflammation and hepatic stellate cell activation but does not exacerbate experimental liver fibrosis in mice

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant and high-affinity ligand for the aryl hydrocarbon receptor (AhR). Increasing evidence indicates that AhR signaling contributes to wound healing, which involves the coordinated deposition and remodeling of the extracellular matrix. In the liver, wound healing is attributed to the activation of hepatic stellate cells (HSCs), which mediate fibrogenesis through the production of soluble mediators and collagen type I. We recently reported that TCDD treatment increases the activation of human HSCs in vitro. The goal of this study was to determine how TCDD impacts HSC activation in vivo using a mouse model of experimental liver fibrosis. To elicit fibrosis, C57BL6/male mice were treated twice weekly for 8weeks with 0.5ml/kg carbon tetrachloride (CCl4). TCDD (20μg/kg) or peanut oil (vehicle) was administered once a week during the last 2weeks. Results indicate that TCDD increased liver-body-weight ratios, serum alanine aminotransferase activity, and hepatic necroinflammation in CCl4-treated mice. Likewise, TCDD treatment increased mRNA expression of HSC activation and fibrogenesis genes, namely α-smooth muscle actin, desmin, delta-like homolog-1, TGF-β1, and collagen type I. However, TCDD treatment did not exacerbate fibrosis, nor did it increase the collagen content of the liver. Instead, TCDD increased hepatic collagenase activity and increased expression of matrix metalloproteinase (MMP)-13 and the matrix regulatory proteins, TIMP-1 and PAI-1. These results support the conclusion that TCDD increases CCl4-induced liver damage and exacerbates HSC activation, yet collagen deposition and the development of fibrosis may be limited by TCDD-mediated changes in extracellular matrix remodeling.

Effect of Punica Granatum (Pomegranate) on serum ALT and AST in Carbon tetrachloride induced liver damage in Wistar Albino Rats

Background: Liver diseases are associated with significant morbidity and mortality. Punica granatum may have free radical scavenging activity and it can be used for the prevention and treatment of liver damage.Objective: To observe the hepatoprotective effects of Punica granatum on CCl4 induced liver damage in rats.Methods: The experimental study was carried out in the Dept of Physiology, Dhaka Medical Ccollege, Dhaka from July 2013 to June 2014. For this purpose, 36 wistar albino rats were studied. After acclimatization for 7 days, they were divided into two groups-control and experimental group. Control group were subdivided into BC (Baseline control), CC (CCl4 treated control) and SC (Silymarin treated control). Experimental group were subdivided into CP-APT (CCl4 pretreated and aqueous extract of pomegranate treated), CP-EPT (CCl4 pretreated and ethanolic extract of pomegranate treated) and APP-CT (Aqueous extract of pomegranate pretreated and CCl4 treated). Each sub group consisted of 6 rats. All rats received basal diet for 8 days. In addition to basal diet on 8th day, BC received single dose olive oil and CC received CCl4. Rats of SC received silymarin for 8consecutive days. In experimental groups, CP-APT received aqueous extract of Pomegranate and CP-EPT received ethanolic extract of Pomegranate for 8consecutive days. Moreover, APP-CT received aqueous extract of Pomegranate for 8 consecutive days and CCl4 only on 8th day. All rats were sacrificed on 9th day and then blood samples were collected. Serum ALT and AST levels were estimated by using standard laboratory kits. Statistical analysis was done one way ANOVA and Bonferroni test.Results: The mean serum AST and ALT levels were significantly (p&lt;0.001) higher in CC in comparison to those of BC. Serum AST and ALT levels of all experimental groups were significantly (P&lt;0.001) lower than CC. Silymarin used as a standard reference also exhibited significant hepatoprotective activity against CCl4 induced hepatotoxicityConclusion: From the result of present study it can be concluded that, Pomegranate may have hepatoprotective effect by lowering ALT and AST levelsBangladesh Soc Physiol. 2016, June; 11(1): 23-28

Anti-hepatic fibrosis effects of a novel turtle shell decoction by inhibiting hepatic stellate cell proliferation and blocking TGF-β1/Smad signaling pathway in rats.

Hepatic fibrosis (HF), a wound-healing response to a variety of chronic stimuli, is characterized by the excessive synthesis of extracellular matrix (ECM) proteins by hepatic stellate cells (HSC) and eventually the development of hepatic cirrhosis. Turtle shell pill (TSP) is a common traditional Chinese medicine used for preventing and treating HF and early hepatic cirrhosis, but its side-effects and the shortage of ingredients limit its clinical application. In addition, its mechanism of action is not clear. In the present study, we first improved the original formula of TSP to produce a novel turtle shell decoction (NTSD) with less toxicity and easier accessible materials. In a carbon tetrachloride (CCl4)-induced HF rat model, we observed that NTSD and TSP had similar effects on the improvement of liver functions in rats, including a decrease in serum alanine amino transferase (ALT) and aspartate amino transferase (AST) serum concentrations and increased albumin content in addition to a marked attenuation of CCl4-induced liver damage and fibrosis. NTSD containing rat serum inhibited rat liver stellate cell line HSC-T6 cell proliferation and induced cell apoptosis invitro. Moreover, the NTSD treatment significantly decreased the transforming growth factor beta 1 (TGF-β1) and Smad3 gene expression and increased inhibitory Smad7 gene expression in liver tissues of HF rats, suggesting that NTSD inhibited the ECM expression of HSC by downregulating the TGF-β1/Smad signaling pathway. The results of our rat model study revealed that NTSD showed good invitro and invivo anti-HF effects via proliferation inhibition and the induction of apoptosis of HSCs and blocked the TGF-β1/Smad signaling pathway.

ANTI-HEPATOTOXIC PROPERTY OF ROOTS AND LEAVES OF CHASSALIA CURVIFLORA (WALL.) THWAITES AGAINST CCL4 INDUCED LIVER DAMAGE IN RATS

In the present study the roots and leaf ethanolic extracts of Chassalia curviflora were screened for their anti hepatotoxic and anti oxidant effects in experimentally induced liver injury by carbon tetra chloride. Liver serum marker enzymes as well as antioxidant enzymes mainly superoxide dismutase, catalase and glutathione levels were determined. The plant root and leaf ethanolic extracts at 50, 100, 200 mg concentrations significantly (**P ≤ 0.05) reduced the elevated serum hepato specific enzyme [serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (SAKP), serum bilirubin (SB)] and cholesterol levels induced by CCl4. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and non enzymatic reduced glutathione (GSH) levels were increased whereas malondialdehyde (MDA) level was reduced by the extracts. Compared to the leaf extract, root extract significantly reduced serum hepato parameters and increased the levels of anti-oxidant enzymes in a dose dependent manner. The results were comparable to that of silymarin, reference drug used for the study. The histopathological studies also supported the biochemical findings. Acute toxicity studies revealed that it is safe for pharmacological uses upto 2000mg/kg. The present study scientifically validated the traditional use of plant root in hepatoprotection.

Hepatoprotective activity of Ceriops decandra (Griff.) Ding Hou mangrove plant against CCl4 induced liver damage

In folklore medicine, Ceriops decandra is used to treat hepatitis. However, a scientific evaluation has not been performed. Thus, the present study was carried out to identify the hepatoprotective activity of plant parts (leaf, bark, collar, flower and hypocotyls) of C. decandra. In vitro antioxidant studies were carried out with DPPH, HRSA, NO, FRAP and LPO assays. The LD50 was calculated and in vivo hepatoprotective activity was carried out with the leaf extract, which was found to be the most potent. The in vivo hepatoprotective activity was performed as follows: Group 1, control animals; Group 2, carbon tetrachloride (CCl4)-treated animals; Group 3, silymarin (100mgkg−1 bw p.o.) treated animals; Groups 4, 5 and 6, C. decandra treatment groups (100, 200 and 400mgkg−1 bw). Histopathological scores were calculated with standard protocols. Of the selected different plant parts, the leaf extract showed maximum antioxidant scavenging properties. A study of the oral acute toxicity found C. decandra extract to be non-toxic up to 2000mgkg−1 bw. The in vivo hepatoprotective nature of the leaf extract was identified as dose dependent and the levels of SGOT, SGPT, ALP, bilirubin, CHL and LDH were found to be significantly decreased (p<0.05) compared with hepatotoxin groups. Histopathological scores did not show any significant variations between control and high dose (400mgkg−1 bw) of leaf extract-treated animals. Preliminary phytochemical analysis of the leaf extract revealed the presence of phenolic groups, alkaloids, triterpenoids, flavonoids, catechin and anthraquinone. In conclusion, the hepatoprotective nature of the C. decandra leaf extract might be due to the occurrence of unique secondary metabolites and their antioxidant scavenging properties.

Turmeric extract and its active compound, curcumin, protect against chronic CCl4-induced liver damage by enhancing antioxidation.

BackgroundCurcumin, a major active component of turmeric, has previously been reported to alleviate liver damage. Here, we investigated the mechanism by which turmeric and curcumin protect the liver against carbon tetrachloride (CCl4)-induced injury in rats. We hypothesized that turmeric extract and curcumin protect the liver from CCl4-induced liver injury by reducing oxidative stress, inhibiting lipid peroxidation, and increasing glutathione peroxidase activation.MethodsChronic hepatic stress was induced by a single intraperitoneal injection of CCl4 (0.1 ml/kg body weight) into rats. Turmeric extracts and curcumin were administered once a day for 4 weeks at three dose levels (100, 200, and 300 mg/kg/day). We performed ALT and AST also measured of total lipid, triglyceride, cholesterol levels, and lipid peroxidation.ResultWe found that turmeric extract and curcumin significantly protect against liver injury by decreasing the activities of serum aspartate aminotransferase and alanine aminotransferase and by improving the hepatic glutathione content, leading to a reduced level of lipid peroxidase.ConclusionsOur data suggest that turmeric extract and curcumin protect the liver from chronic CCl4-induced injury in rats by suppressing hepatic oxidative stress. Therefore, turmeric extract and curcumin are potential therapeutic antioxidant agents for the treatment of hepatic disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1307-6) contains supplementary material, which is available to authorized users.

Hepatoprotective Effect of Low Doses of Caffeine on CCl4-Induced Liver Damage in Rats

ABSTRACTSeveral studies have shown the hepatoprotective effect of the consumption of coffee and tea, which is mainly attributed to caffeine. Many experimental studies have demonstrated this effect; however, these studies used high caffeine doses that are not related to human consumption. The aim of this study was to evaluate the hepatoprotective effect of low doses of caffeine on carbon tetrachloride (CCl4)-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and CAFF10) were evaluated in chronic liver damage induced by CCl4 (0.75 mL/kg) in rats. CAFF treatment was administered once a day and CCl4 administration was twice weekly for 10 weeks. Liver function tests (biochemical markers) and functional (sleeping time) and histological (hematoxylin-eosin and Masson trichrome stains) parameters were carried out at the end of damage treatment. Daily treatments of CAFF5 and CAFF10 exhibited a hepatoprotective effect supported by a decrease of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) serum activities and bilirubin serum levels compared with control and also restored serum albumin levels and liver glutathione (GSH). Moreover, CAFF prevented CCl4-induced prolongation in pentobarbital sleeping time and a decrease of liver fibrosis and cell death. Our results demonstrated that low doses of CAFF exert a hepatoprotective effect against CCl4 -induced liver damage in rats.