Carbon Tetrachloride-induced Hepatotoxicity Research Articles

Hepatoprotective effects of Berberis vulgaris leaf extract on carbon tetrachloride-induced hepatotoxicity in rats.

INTRODUCTION:Hepatic sickness is a serious problem for human health. The researchers are interested in using medicinal plants including barberry to cure many of these sicknesses. In this study, the effect of hydroalcoholic extract of Berberis vulgaris leaf on hepatic protection was assessed in rats.MATERIALS AND METHODS:Forty healthy male Wistar rats were divided randomly into five groups (n = 8): Group 1 (healthy control), intraperitoneal injection of olive oil; Group 2 (hepatotoxic control), intraperitoneal injection of carbon tetrachloride and daily gavage of distilled water; and testing groups, intraperitoneal injection of carbon tetrachloride along with daily gavage of B. vulgaris leaf extract 40, 80, and 120 mg/kg of weight, respectively. After 6 weeks, the following were checked: enzyme level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), as well as serum level of total protein (TP), albumin (ALB), and histopathological status of the liver.RESULTS:The level of AST, ALP, and ALT was increased to 109 (IU/L), 95(IU/L), and 71(IU/L), respectively, in hepatotoxic control group than healthy control group, and there was a decrease of 0.86 (g/dl) and 0.04 (g/dl) in TP and ALB levels, respectively. The B. vulgaris extract in every three doses caused a significant decrease in hepatic enzymes level. However, the TP had a significant increase in 80 and 120 mg/kg of body weight. Regarding ALB, there was no significant difference among these groups. The histopathological results were not conformed to biochemical findings.CONCLUSION:Using the appropriate dose of B. vulgaris leaf extract can help the improvement of laboratory symptoms of fatty liver.

Hepatoprotective Activity of Hydroalcohilic Extract of Annona squamosa Seeds

Ethnopharmacological Relevance: Traditionally, Annona Sqamosa Linn. has been used for treatment of cancer, diabetes, microbial infection, cardiac disease, jaundice and other liver related disorder. Hence the current work aims to explore the hepatoprotective of the Annona Sqamosa (AS) seeds. Aim of the study: The main objective of study is to evaluate hepatoprotective activity of the hydroalcoholic extract of seeds of Annona Squamosa Linn. using the carbon tetrachloride induced liver toxicity in rats. Material and methods: The activity was evaluated against carbon tetrachloride induced hepatotoxicity by measuring the levels of serum enzymes such as SGOT, ALP, SGPT and total bilirubin for liver function tests. Six groups of rats were used (n=6) and administered orally once daily with normal saline (normal control), carbon tetrachloride (toxic control), or ASE (100, 200, and 400 mg/kg) for 7 days, followed by the hepatotoxicity induction. Results: The extract showed significant hepatoprotective activity at 100 mg/kg, 200 mg/kg, and 400mg /kg b.w by decreasing the levels of SGOT, SGPT, ALP and total bilirubin as compared to toxic control group. Conclusions: The hydroalcoholic ASE extract have potential of liver protection which could be attributed for further investigation

Evaluating therapeutic potential of coriander seeds and leaves (Coriandrum sativum L.) to mitigate carbon tetrachloride-induced hepatotoxicity in rabbits

Objective: To evaluate the hepatic and renal protective potential of coriander seeds and leaves using animal feed model. Methods: Coriander seeds- and leaves-based sauces were administrated to normal (Study I) and carbon tetrachloride (2 mL/kg B.W.)-induced hepatotoxic rabbits (Study II). Hepatic and renal biomarkers like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, superoxide dismutase and catalase were measured. Results: Coriander leaves-based sauce exerted more decline (P

Sildenafil, a phosphodiesterase-5 inhibitor, offers protection against carbon tetrachloride-induced hepatotoxicity in rat.

Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5'-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl4). CCl4 (0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline. Sildenafil (5 mg, 10 mg, and 20 mg/kg, p.o.) was administered to CCl4-treated rats. CCl4 significantly increased the serum levels of gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and reduced total protein (TP) (p<0.05). Pretreatment with sildenafil moderately reduced ALP, AST, and ALT activities with modest increase in TP level. CCl4-induced changes in the antioxidant status of the liver were significantly improved by sildenafil, especially at the lowest dose of 5 mg/kg by elevating the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and preventing lipid peroxidation (p<0.05). Sildenafil did not significantly alter the total cholesterol and triglyceride levels. However, high-density lipoprotein (HDL) level was significantly increased by sildenafil (p<0.05). The results from this study suggest that sildenafil, when used at low doses, may be a useful pharmacological protective agent against CCl4-induced hepatotoxicity.

Hepatoprotective effect of food preservatives (butylated hydroxyanisole, butylated hydroxytoluene) on carbon tetrachloride-induced hepatotoxicity in rat.

Carbon tetrachloride (CCl4), a hepatotoxic agent is widely used to study the toxic mechanisms in experimental animals. This study was carried out to establish the hepatoprotective measures of food preservative antioxidants butylated hydroxyanisole and butylated hydroxytolune (BHA, BHT) when mixed with food towards carbon tetrachloride (CCl4) intoxication (230mg/kg b wt/rat/day) in rat. Biochemical markers like serum glutamate pyruvate tranaminase (AST), serum glutamate oxaloacetate transaminase (ALT), alkaline phosphatase (ALP) and bilirubin content, antioxidant enzymes such as SOD, CAT, GPx, and malondialdehyde (MDA) as the end product of lipid peroxidanion were measured. The results had shown the elevated level of AST (121.16%), ALT (124.68%), ALP (122.41%) an, bilirubin content (57.14%) after CCl4 treatment. Marked decrease of activity of antioxidant enzymes such as SOD (85.36%), CAT (67.47%), GPx (50.7%) had indicated that the ROS mediated toxicity and pretreatment of BHA and BHT restored the activity of these enzymes. High level of MDA content with reduced GSH value was also observed due to oxidative stress. The hepatic antioxidant status was restored with the food preservative (BHA, BHT) antioxidant treatment which had indicated the significant protective effect against CCl4 induced hepatotoxicity and finally confirmed by histopathological studies.

White butterfly (Clerodendrum volubile) leaf extract protects against carbon tetrachloride-induced hepatotoxicity in rats

Currently, there is increasing attention towards flavonoids and phenolic compounds of plant origin because of their association with decrease in the incidence of cardiovascular diseases and different types of cancer. The present study investigates the protective effect of Clerodendrum volubile (C. volubile) methanolic extracts against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Control rats (group I) received olive oil (1 mL/kg, i.p.), group II received CCl4 in olive oil (1 ml/kg, i.p.) to induce hepatotoxicity, groups III, IV and V were pretreated with leaf extract of C. volubile at 125 mg/kg, 250 mg/kg and 500 mg/kg body weight respectively for 14 days prior to CCl4 administration, group VI received vitamin E (100 mg/kg, p.o.) as standard antioxidant to compare with antioxidant effects of the extract. CCl4 hepatotoxicity, characterized by significant (P < 0.05) increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), hepatic degeneration, and inflammation was attenuated by C. volubile methanolic extracts. The serum lipid parameters which include high density lipoprotein (HDL) and low density lipoprotein (LDL) were significantly (P < 0.05) decreased, and increased respectively by CCl4. Methanolic extracts of C. volubile significantly prevented the decrease in the level of HDL and the increase in LDL in a dose-dependent manner (P < 0.05). Decrease in total protein induced by CCl4 was moderately increased following administration of methanolic extracts of C. volubile. Lipid peroxidation was significantly (P < 0.05) reduced while the reduced glutathione (GSH) level and the activities of hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) were significantly elevated by C. volubile extract in the CCl4-treated rats. Our findings indicate that C. volubile extract has a significant protective effect against CCl4-induced hepatotoxicity in rats which may be due to its antioxidant properties which is comparable to the reference antioxidant, vitamin E, used in this study.

A composition of medicinal plants with an enhanced ability to suppress microsomal lipid peroxidation and a protective activity against carbon tetrachloride-induced hepatotoxicity

Treatment of liver injury induced by various toxicants represents a serious clinical challenge. Here, we utilized the ability of natural agents to inhibit microsomal lipid peroxidation (LPO) as the in-vitro screening paradigm for selecting efficacious tissue-protective combinations of cooperatively acting medicinal plants. Based on screening of 70 water-ethanol extracts obtained from different parts of 65 plants we prepared a highly active phytocomposition (PC-1) containing oregano (Origanum vulgare), wild thyme (Thymus serpyllum) and coltsfoot (Tussilago farfara) aerial parts, valerian (Valeriana officinalis) leaves and little-leaf linden (Tilia cordata) flowers. PC-1 extract exhibited the strongest anti-PLO and antihemolytic effects in vitro compared to those of the individual plants and other compositions tested. Using luciferase reporter assay and Western blotting in HepG2 human hepatocellular carcinoma cells, we found that PC-1 extract activated the Nrf2/antioxidant response element signaling pathway more effectively than the extracts of other phytocompositions. Importantly, oral administration of PC-1 extract (100–200 mg/kg) markedly ameliorated liver injury in rats acutely or chronically intoxicated by carbon tetrachloride. This was evidenced by improved liver histology, blood chemistry parameters, and microsomal LPO status and superoxide dismutase activity. In addition, treatment with PC-1 extract salvaged the osmotic resistance of erythrocytes in carbon tetrachloride-intoxicated rats. Collectively, these data support the strategy of in-vitro plant selection for developing efficacious tissue-protective phytocompositions.

Enhanced pharmacokinetic behavior and hepatoprotective function of ginger extract-loaded supersaturable self-emulsifying drug delivery systems

The aim of present study was to enhance the nutraceutical properties of ginger extract (GE) by employing supersaturable self-emulsifying drug delivery systems (S-SEDDS). SEDDS of GE (SEDDS/GE), consisting of medium-chain triglyceride, lysolecithin and glycerin, was produced. To prepare S-SEDDS of GE (S-SEDDS/GE), hydroxypropyl methylcellulose was added to the SEDDS/GE asa precipitation inhibitor. Physicochemical, pharmacokinetic, and hepatoprotective properties of GE formulations were characterized. Both formulations improved the dissolution behavior of GE due to the formation of fine micelles with a median diameter of ca. 110nm. After oral administration of GE samples in rats, the relative bioavailabilities of 6-gingerol and 8-gingerol in the S-SEDDS/GE-treated group were ca. 3-fold higher than those of GE-treated group, respectively. Repeated oral administration of GE/S-SEDDS (100mg-GE/kg) provided a hepatoprotective effect in a rat model of carbon tetrachloride-induced hepatotoxicity. From these observations, the S-SEDDS approach might be efficacious for enhancing the nutraceutical properties of GE.

Hepatoprotective effect of fraxin against carbon tetrachloride-induced hepatotoxicity in vitro and in vivo through regulating hepatic antioxidant, inflammation response and the MAPK-NF-κB signaling pathway

Fraxin, a main active component isolated from Cortex Fraxini, possesses a variety of bioactivities. However, there is a research gap in studies related to the hepatoprotective activity of fraxin against carbon tetrachloride (CCl4)-induced liver damage has been rarely studied. Thus, the purpose of this study is to evaluate the protective effect of fraxin against CCl4-induced liver damage in mice as well as in HepG2 cells, in addition to further improve the underlying mechanisms of hepatoprotective effect for fraxin. In mice model, pretreatment with fraxin (10, 20 or 40mg/kg) along with CCl4 significantly alleviated liver damage as indicated by the decreased levels of liver index, liver marker enzymes, lipid peroxidation, inflammatory mediators, increased levels of the antioxidant enzymatic and non-enzymatic defense parameters, and improved hepatic histopathology changes. Further, the results of the in vitro study conducted in HepG2 cells indicated that the CCl4-induced changes were significantly ameliorated by pretreatment of fraxin. Moreover, immunohistochemistry staining and western blot assay demonstrated that pretreatment with fraxin can down-regulate CCl4-induced protein expression of MAPKs, NF-κB and COX-2. Overall, these studies indicate that fraxin exhibits hepatoprotective effect against CCl4-induced liver damage by reducing inflammation response, suppressing oxidative stress and lipid peroxidation and enhancing antioxidant activity. The underlying mechanisms of fraxin in CCl4-induced acute liver injury may be due to inhibition of MAPK and NF-κB activation. It is possible for fraxin to be used as a hepatoprotective agent.

Effect of zinc sulphate and Essentiale® Forte in managing carbon tetrachloride-induced hepatotoxicity in adult Wistar rats

Objectives: The aim of this study was to assess and compare the ameliorative effect of zinc sulphate and Essentiale® Forte on the histomorphology and lipid histochemistry of carbon tetrachloride (CCl4)-induced hepatic injury in adult Wistar rats. Methods: Twenty-five adult Wistar rats, weighing between 150 g and 170 g, were used for the study. The animals were divided into five groups A, B, C, D and E (n=5). Group A received 0.7 ml/kg of olive oil orally. Groups B, C, D and E were administered CCl4 (0.7 ml/kg, orally) for 1 week in 1:1 dilution with olive oil. After CCl4 administration, Group C was treated with Essentiale® Forte (4.5 mg/kg/bw, orally) for four weeks. Group D was treated with zinc sulphate (7 mg/kg/bw, orally) daily for four weeks. Group E received zinc sulphate (7 mg/kg/bw, orally) and Essentiale® Forte (4.5 mg/kg/bw, orally) for a period of 4 weeks, while Group B was left untreated. Animals were left for another one week and subsequently sacrificed under ether anaesthesia. The liver was harvested, weighed and divided into two parts for histological and histochemical studies. Results: Histological analysis showed that treatment of liver with CCl4 caused hepatotoxicity as marked by presence of inflammatory cells and distortion in the connective tissue fibers, as compared to the ones treated with zinc sulphate and or Essentiale® Forte which restored the hepatic histoarchitecture and protected the liver tissue from fatty and degenerative changes. Conclusion: This study showed that combination of Essentiale® Forte and zinc supplement offered better ameliorative effects on the liver of Wistar rats following CCl4-induced hepatotoxicity compared with separate administration of either Essentiale® Forte or zinc sulphate.

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.

Effects of Alternanthera sessilis on Liver Function in Carbon Tetra Chloride Induced Hepatotoxicity in Wister Rat Model

Alternanthera sessilis commonly known as 'sessile joy weed' or 'dwarf copperleaf' is found throughout the hotter parts of India up to an altitude of 1200m2. In Assam, the plant has been traditionally used in the treatment of jaundice along with other ailments. The study focuses primarily on the evaluation of hepatoprotective activity of the plant with special references to its putative protective role in carbon tetrachloride induced liver injury on Wister albino rat. The in vivo hepatoprotective activity of the methanolic extract at the dose of 250mg/kg body weight was highly effective in controlling SGPT, SGOT, ALP, serum cholesterol and serum bilirubin level as compared to silymarin. The said extract also significantly lowered the lipid profile caused by CCl4. The activity shown by methanolic extract of the whole plant of A. sessilis is of considered importance and thus justified its use in controlling hepatic diseases in traditional treatment system.

Vitamin D3-induced hypercalcemia increases carbon tetrachloride-induced hepatotoxicity through elevated oxidative stress in mice.

The aim of this study was to determine whether calcium potentiates acute carbon tetrachloride (CCl4) -induced toxicity. Elevated calcium levels were induced in mice by pre-treatment with cholecalciferol (vitamin D3; V.D3), a compound that has previously been shown to induce hypercalcemia in human and animal models. As seen previously, mice injected with CCl4 exhibited increased plasma levels of alanine aminotransferase, aspartate aminotransferase, and creatinine; transient body weight loss; and increased lipid peroxidation along with decreased total antioxidant power, glutathione, ATP, and NADPH. Pre-treatment of these animals with V.D3 caused further elevation of the values of these liver functional markers without altering kidney functional markers; continued weight loss; a lower lethal threshold dose of CCl4; and enhanced effects on lipid peroxidation and total antioxidant power. In contrast, exposure to V.D3 alone had no effect on plasma markers of liver or kidney damage or on total antioxidant power or lipid peroxidation. The potentiating effect of V.D3 was positively correlated with elevation of hepatic calcium levels. Furthermore, direct injection of CaCl2 also enhanced CCl4-induced hepatic injury. Since CaCl2 induced hypercalcemia transiently (within 3 h of injection), our results suggest that calcium enhances the CCl4-induced hepatotoxicity at an early stage via potentiation of oxidative stress.

Correction to: Krithika, Jyothi, Prasantha, and Ramtej, Mechanism of protective effect of phyllanthin against carbon tetrachloride-induced hepatotoxicity and experimental liver fibrosis in mice

"Correction to: Krithika, Jyothi, Prasantha, and Ramtej, Mechanism of protective effect of phyllanthin against carbon tetrachloride-induced hepatotoxicity and experimental liver fibrosis in mice." Toxicology Mechanisms and Methods, 27(6), p. 476

Urinary metabonomics study of the hepatoprotective effects of total alkaloids from Corydalis saxicola Bunting on carbon tetrachloride-induced chronic hepatotoxicity in rats using 1H NMR analysis

Chronic liver injury has been shown to cause liver fibrosis due to the sustained pathophysiological wound healing response of the liver, and eventually progresses to cirrhosis. The total alkaloids of Corydalis saxicola Bunting (TACS), a collection of important bioactive ingredients derived from the traditional Chinese folk medicine Corydalis saxicola Bunting (CS), have been reported to have protective effects on the liver. However, the underlying molecular mechanisms need further elucidation. In this study, the urinary metabonomics and the biochemical changes in rats with carbon tetrachloride (CCl4)-induced chronic liver injury due to treatment TACS or administration of the positive control drug-bifendate were studied via proton nuclear magnetic resonance (1H NMR) analysis. Partial least squares-discriminate analysis (PLS-DA) suggested that metabolic perturbation caused by CCl4 damage was recovered with TACS and bifendate treatment. A total of seven metabolites including 2-oxoglutarate, citrate, dimethylamine, taurine, phenylacetylglycine, creatinine and hippurate were considered as potential biomarkers involved in the development of CCl4-induced chronic liver injury. According to pathway analysis using identified metabolites and correlation network construction, the tricarboxylic acid (TCA) cycle, gut microbiota metabolism and taurine and hypotaurine metabolism were recognized as the most affected metabolic pathways associated with CCl4 chronic hepatotoxicity. Notably, the changes in 2-oxoglutarate, citrate, taurine and hippurate during the process of CCl4-induced chronic liver injury were significantly restored by TACS treatment, which suggested that TACS synergistically mediated the regulation of multiple metabolic pathways including the TCA cycle, gut microbiota metabolism and taurine and hypotaurine metabolism. This study could bring valuable insight to evaluating the efficacy of TACS intervention therapy, help deepen the understanding of the hepatoprotective mechanisms of TACS and enable optimal diagnosis of chronic liver injury.

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.

Supplementation with Lycium chinense fruit extract attenuates methionine choline-deficient diet-induced steatohepatitis in mice

Previous studies have reported that Lycium chinense fruit extract (LFE) attenuates carbon tetrachloride-induced hepatotoxicity. Here, we investigated whether dietary LFE supplementation prevents non-alcoholic steatohepatitis (NASH) development induced by a methionine-choline-deficient (MCD) diet. C57BLS/J-m mice were fed a normal chow diet or an MCD diet with or without LFE for 4weeks by daily oral gavage. MCD-diet-fed mice exhibited significantly lower body weights and a higher degree of steatohepatitis with increased steatosis, oxidative stress, inflammation and fibrosis, which were partially or totally prevented by dietary supplementation with LFE. The efficacy of LFE was comparable to the effect elicited by treatment with betaine, a main constituent of LFE. Mechanistically, the hepatoprotective effects were associated with reduced JNK and increased ERK activities. This study suggests the therapeutic potential of dietary LFE supplementation for preventing the development and progression of non-alcoholic fatty liver disease in patients with higher risk factors for NASH.

Ameliorative Effect of the Flavonoid Rich Fraction of Monodora myristica (Gaertn) Dunel Seed Extract against Carbon Tetrachloride-Induced Hepatotoxicity and Oxidative Stress in Rats

The study investigated the protective effect of the flavonoid rich fraction (FRF) of M. myristica on carbon tetrachloride induced hepatotoxicity and oxidative stress in experimental animals. Wistar albino rats of both sexes were maintained on 1.0 ml/kg b.wt of carbon tetrachloride to induce hepatotoxicity and oxidative stress. Added to this, the animals received FRF at a dose of 250 or 500 and 100 mg/kg b.wt of silymarin for 8 days. At the end of the experiment, levels of serum hepatic enzyme biomarkers (SGOT, SGPT and SALP) as well as lipid peroxidation product (MDA) and total bilirubin were significantly raised in the CCl4 treated groups. Conversely, CCl4 administration elicited obvious decline in enzymatic antioxidants activities and non-enzymatic antioxidants (GSH, CAT, SOD, vitamin C, vitamin E) co-administration with FRF of M. myristica at varying doses as well as silymarin substantially decreased the elevated levels of the serum hepatic enzyme biomarkers as well as MDA in the CCl4 treated groups in a dose dependent manner. Additionally, FRF of M. myristica exhibited reversal potential on CCl4 toxicity at the tested doses as its administration resulted to a pronounced increase in GSH, SOD and CAT levels. Histopathological results demonstrate that FRF of M. myristica is effectual in the amelioration of hepatic damage and oxidative stress arising from CCl4 induced hepatotoxicity. These results establish the effectiveness of the flavonoids of M. Myristica in the amelioration of hepatic damages arising from CCl4-induced toxicity which is manifest by the bioaccumulation of free radicals in our animal models.

Hepatoprotective activity of aqueous and ethanolic Bixa orellana L. leaf extracts against carbon tetrachloride-induced hepatotoxicity

Background: There is an increasing incidence of liver failure and lack of effective drugs for liver diseases. Aim and Objective: This study identified the phytochemicals present in aqueous and ethanolic Bixa orellana L. leaf extracts and investigated the hepatoprotective activity against carbon tetrachloride (CCl4)-induced hepatotoxicity in mice. Specifically, the study compared serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and examined liver tissues histopathology. Materials and Methods: Aqueous and ethanolic B. orellana L. leaf extracts were prepared and screened for phytochemical contents. An oral dose of 500 mg/kg body weight was identified from toxicity test and administered to albino mice. Microscopic examination of the liver tissues assessed the extent of hepatic injury. Serum AST and ALT levels were compared using one-way analysis of variance with Bonferroni post hoc analysis at 5% level of significance using Stata/SE V12.0 software. Results: B. orellana L. leaves contained alkaloids, anthraquinones, sugars, and tannins. Aqueous and ethanolic leaf extracts of B. orellana L. did not show any toxicity up to 2000 mg/kg body weight oral dose in mice. Pre-treatment for 7 days before CCl4 administration significantly prevented elevation of serum AST and ALT levels with histopathologic findings showing a protective effect on the hepatocytes. Conclusion: B. orellana L. leaves have potent hepatoprotective activity against oxidative damage.

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.