Carbon Tetrachloride-induced Liver Damage Research Articles

Pericopsis laxiflora (Baker) stem bark extract is protective against carbon tetrachloride-induced acute liver damage by modulation of oxidative stress and inflammation

The present study aimed to investigate the hepatoprotective activity of the hydroethanolic (HSE) and methanolic extracts (MSE) of Pericopsis laxiflora stem bark on carbon tetrachloride-induced hepatotoxicity in rats. The stem bark of P. laxiflora was extracted with 50% ethanol and methanol. Hepatoprotective activities were assessed using the CCl4 model and tested against extracts at 100, 250, and 500 mg/kg bwt. Biochemical, antioxidant enzymes and proinflammatory cytokines in liver homogenate were assayed. Treatment with HSE and MSE resulted in a significant increase in SOD, CAT, and GSH levels and a significant decrease in MDA and MPO levels in livers of CCl4 treated rats. There was also restoration of liver biomarkers and pro-inflammatory cytokines to near-normal levels. The present investigation suggests P. laxiflora extracts possess good hepatoprotective properties. This could be attributed in part to the inhibitory effect of the extracts on oxidative stress and the suppression of proinflammatory cytokines.

Effects of Ethyl Acetate Fraction of Mangifera haden Seeds on Carbon Tetrachloride Induced Hepatotoxicity in Albino Rats

The present study investigated the effects of ethyl acetate fraction of Mangifera haden seeds on carbon tetrachloride-induced liver damage in wistar albino rats. The phytochemical compositions and acute toxicity studies of crude extract and Mangifera haden seed fraction were determined using standard methods. Albino rats (60) randomly grouped into twelve of five rats each were used for this study. Determination of total bilirubin and protein, lipid peroxidation, liver enzymes marker, antioxidant enzymes, glutathione, lipid profile analysis and histological examination were carried out using standard methods. Phytochemical constituents of crude extract and ethyl acetate fraction of Mangifera haden seed showed that they contain relative amount of flavonoids, phenolics, saponins, tannins, terpenoids, triterpenes, alkaloids and coumarins. Liver injury was induced with carbon tetrachloride (CCl4) at a dose of 1.0 ml/kg body weight of the animals. All the CCl4 intoxicated rats displayed hyperlipidemia as shown by their elevated levels of serum total cholesterol (TC), triacylglycerol (TAG), low density lipoprotein (LDL), and reduction in high density lipoprotein (HDL) levels. The administration of ethyl acetate fraction of Mangifera haden seeds significantly (P = 0.05) lowered the levels of serum TC, TAG, LDL, and increased HDL levels. The level of serum malondialdehyde (MDA) significantly (P = 0.05) increased in the CCl4 group as compared to the normal and treated groups. The elevated level of serum MDA decreased (P = 0.05) significantly at the treatment of rats with 200, 400 and 600 mg/kg of ethyl acetate fraction. The rats treated with CCl4 produced significant (P = 0.05) increase in serum ALT, AST and ALP when compared to the normal group. Animals treated with varying doses of ethyl acetate fraction produced significant (P = 0.05) reduction of serum ALT, AST and ALP activities when compared to the CCl4-untreated group. The activities of hepatic antioxidant enzymes (SOD, CAT and GPx) and glutathione concentration significantly (P = 0.05) decreased in CCl4­-untreated group compared to the normal group. The decreased activities of the antioxidant enzymes and glutathione concentration in CCl4 intoxicated rats were ameliorated/modulated more effectively in rats treated with 200, 400 and 600 mg/kg ethyl acetate fraction of Mangifera haden seed. Total bilirubin (TB) concentrations significantly (P = 0.05) increased in CCl4-untreated group when compared to the normal group. Oral treatment of rats with varying doses (200, 400, 600 mg/kg) of ethyl acetate fraction caused a significant (P = 0.05) decrease in the serum TB levels. Administration of CCl4 showed a reduction in serum total proteins. Treatment of the animals with 200, 400 and 600 mg/kg of ethyl acetate fraction caused significant (P = 0.05) increase in serum total potein. Histological examination showed hepatoprotective properties of plant’s fractions. The compounds found in the different fractions (ethyl acetate and n-hexane) of Mangifera haden seeds are 9-Octadecenoic acid (Z)-, methyl ester, (Z) –Oleic acid and so on. Therefore the medicinal importance of the plant is been established.

PHARMACOLOGICAL BENEFITS AND CONSERVATION STRATEGIES OF RHODODENDRON ARBORETUM SM.: A COMPREHENSIVE REVIEW

Rhododendron arboreum, an evergreen shrub native to the Himalayan region, is renowned for its vibrant red flowers and significant medicinal properties. This review explores the diverse pharmacological benefits of R. arboreum, which is integral to traditional medicine in the Himalayas. The plant contains bioactive compounds likeflavonoids, tannins, saponins, and phenolic acids, contributing to its therapeutic potential. Extensive research indicates that R. arboreum exhibits hepatoprotective, antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, and anti-diarrheal properties. The hepatoprotective effects are evident from studies showing its ability to mitigate carbon tetrachloride-induced liver damage and normalize liver enzymes. Its antimicrobial efficacy, particularly against Gram-positive bacteria, is attributed to the bioactive compounds identified in the methanolic extracts of leaves and flowers. Anti-inflammatory and analgesic properties are prominent in the bark extracts, providing potential treatments for chronic inflammation and pain. Additionally, antioxidant studies reveal that R. arboreum extracts reduce oxidative stress and free radical production. Anti-diabetic activities have been demonstrated in streptozotocin-induced diabetic models, showing improved blood glucose levels and lipid profiles. The plant's anti-diarrheal efficacy is supported by animal models indicating reduced gastrointestinal motility and enhanced absorption of water and electrolytes. R. arboreum faces threats from climate change, habitat destruction, and overexploitation, necessitating effective conservation strategies. Genetic studies reveal significant diversity within the species, essential for its adaptation and long-term survival, and offer opportunities for breeding programs. Comprehensive conservation efforts, including habitat protection, sustainable use practices, and the integration of traditional knowledge with scientific research, are imperative. This review highlights the need for sustainable conservation strategies and further research to fully harness the medicinal potential of R. arboreum, ensuring its availability for future therapeutic applications.

Evaluation of the Hepatoprotective potential and Antioxidant activity of 4–Hydroxybenzyl alcohol on Carbon tetrachloride Induced liver damage in Experimental animals

Objective: To study the Hepatoprotective potential and Antioxidant activity of 4 – hydroxybenzyl alcohol in carbon tetrachloride induced liver damage in rats. Materials and methods: Rats were divided into five groups of six animals. Group I was treated with normal saline (Normal control) Group II was treated with the CCl4 hepatotoxic (negative control) Group III was treated with standard drug silymarin (positive control) and Group IV and V was treated with test drug 4–hydroxybenzyl alcohol (Test groups) respectively. On the 7th day, rats were sacrificed and blood was withdrawn by cardiac puncture. The levels and activities of serum biochemical parameters and antioxidant enzymes were then assayed using standard procedures. Results: The hepatoprotective activity of 4–hydroxybenzyl alcohol in this study was compared with the reference drug silymarin. In CCl4 treated animals, 4–hydroxybenzyl alcohol significantly decreased levels of serum transaminases, alkaline phosphatase and total bilirubin, and increased the level of total protein. Treatment with 4 – hydroxybenzyl alcohol resulted in a significant increase in the levels of catalase, superoxide dismutase and reduced glutathione as compared to CCl4 treated group. Histopathology of the liver tissue further supports the biochemical findings confirming the hepatoprotective potential of 4 – hydroxybenzyl alcohol. Conclusions: From the results it can be concluded that 4–hydroxybenzyl alcohol possesses Hepatoprotective effect and antioxidant activity against CCl4 induced liver damage in rats.

A comparative study on the hepatoprotective effect of selenium-nanoparticles and dates flesh extract on carbon tetrachloride induced liver damage in albino rats.

Exposure to environmental pollutants such as carbon tetrachloride (CCL4) causes liver damage. This study aimed to compare the ameliorative activity of the dates flesh extract (DFE) and selenium-nanoparticles (SeNPs) on CCL4-induced hepatotoxicity and if DFE could be a useful alternative supplement. Twenty-four male albino rats were enrolled and randomly divided into four equal groups (6 rats in each group): control group received only basal diet with no medications. Group II received CCL4 in a dose of 0.5 mg/kg intraperitoneal injection twice weekly for four weeks. Group III rats were pretreated with SeNPs in a dose of 2.5 mg/kg once a day orally three times/wk for four weeks alone then combined with the previously described dose of CCL4 for another four weeks. Group IV rats were pretreated with DFE in a dose of 8 ml of the aqueous extract/kg/d orally for four weeks alone then combined with the previously described dose of CCL4 for another four weeks. The liver damage was assessed by estimation of plasma concentration of albumin and enzymes activities of alanine aminotransferase and tissue genes expression. Liver oxidation levels were assessed by measuring the tissue concentration of the malondialdehyde, superoxide dismutase, and the total glutathione. Additionally, inflammatory mediators tumour necrosis factor--α and interleukin-6 were estimated. Detecting the liver's cellular structural damage was done by histopathological and immunohistochemical examination. This study suggests that CCL4-induced liver damage in rats can be protected by administration whether the costly SeNPs or the economical DFE.

The Influential Antioxidant Role Of Coenzyme Q10 and Dehydroepiandrosterone against Carbon Tetrachloride Induced Liver Damage In Male Rats

This study evaluated the protective role of exogenous CoQ10 and DHEA and their combination on CCl4-induced hepatotoxicity in adult male rats. Thirty adult male rats 225-250 grams, 12-14 weeks old, were used in this study and randomly divided into five equal groups, 6 animals each as in the following: Control group (G1): 6 male rats received DMSO 0.5ml/ animal/day orally, First treated group (T1): 6 male rats received daily CCl4 1ml/kg (1:1 olive oil, IP), Second treated group (T2): 6 male rats received CCl4 1ml/ kg and after 1hour injected daily with CoQ10 200 mg/kg IP, Third treated group (T3): 6 male rats received CCl4 1ml/kg and after 1hour injected daily with DHEA 25 mg/kg IP, Fourth treated group (T4): 6 male rats received CCl4 1ml/kg and after 1hour injected daily with a combination of CoQ10 200 mg/kg + DHEA 25 mg/kg IP. The experiment lasted for 28 successive days. The obtained results illustrated that male rats received CCl4 (1ml/kg) caused a significant increase in hepatic enzyme function AST, ALT and ALP, as well as MDA levels, and caused a significant decrease in antioxidant enzyme activity GPx, SOD and CAT levels. In addition, CCl4 also caused various degrees of liver damage, such as dilation and congestion of the central vein with hemorrhage, apparent fatty degeneration and infiltration of inflammatory cells compared to the control group. Whereas, the group treated with CoQ10 200 mg/kg and DHEA 25 mg/kg showed a significant decrease (P< 0.05) in serum AST, ALT and ALP as well as MDA value, and significantly increased in GPx, SOD with the decline in CAT levels compared to the group treated with CCl4 intoxication. It is also observed from the results that the combination of CoQ10 and DHEA caused a highly significant (P < 0.05) decline in AST, ALT and ALP as well as MDA levels, and a significant elevate in GPx, SOD and decline in CAT, and almost return to average level compared to control. As well as, the histopathological examination of the liver revealed that rats treated with CoQ10 and DHEA and their combination had usual central veins and hepatocytes compared to groups treated with CCl4 due to antioxidant, anti-inflammatory and anti-apoptotic properties. It has been concluded that CoQ10 and DHEA have a protective effect against liver damage induced by CCl4 through improving antioxidant enzyme activity in CCl4 treated group leading to a declined MDA level and reduced lipid peroxidation. Thus, CoQ10 and DHEA are potential therapeutic antioxidant agents on hepatotoxicity by suppressing hepatic oxidative stress. Keywords: CoQ10, DHEA, antioxidant, CCl4, hepatic damage, male rat.

Rosmarinic acid exerts anti-inflammatory effect and relieves oxidative stress via Nrf2 activation in carbon tetrachloride-induced liver damage.

Rosmarinic acid (RA) has biological and pharmaceutical properties and shows hepatoprotective potential. However, the hepatoprotective mechanism of RA needs to be further elucidated in vivo and in vitro. This study was aimed to evaluate the protective effect of RA on carbon tetrachloride (CCl4)-induced liver injury and elucidate the hepatoprotective mechanism of RA in vivo and in vitro. In vivo, the mice were orally administrated with RA (10, 20, and 40 mg/kg bw) daily for 28 consecutive days, and 1% CCl4 (5 mL/kg bw, dissolved in peanut oil) was used to induce liver injury. In vitro, the big rat liver (BRL) hepatocytes were pretreated with RA (0.2, 0.4, and 0.8 mg/mL) for 3 h, and then the hepatocytes were treated with CC14 (final concentration, 14 mM) for 3 h to induce cell injury. The related indexes, including hepatic function, oxidative stress, protein expression of nuclear-factor erythroid 2-related factor 2 (Nrf2) pathway, inflammation, histopathological change, hepatocyte apoptosis, and mitochondrial membrane potential, were evaluated. Oral administration of RA to mice considerably decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), triacylglycerols (TG), total cholesterol (TC), total bilirubin (TBIL), hepatic reactive oxygen species (ROS), malondialdehyde (MDA), nitric oxide (NO), 8-hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). RA also increased the levels of hepatic glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) and the protein expressions of Nrf2, quinine oxidoreductase (NQO1), and heme oxygenease-1 (HO-1). Histopathological examinations indicated that RA (20 and 40 mg/kg bw) alleviated the liver tissue injury induced by CCl4. Moreover, RA inhibited the hepatocyte apoptosis caused by CCl4 based on TUNEL assay. In vitro, RA pretreatment remarkably recovered the cell viability and reduced the CCl4-induced elevation of AST, ALT, lactate dehydrogenase (LDH), ROS, and 8-OHdG. Immunohistochemistry staining demonstrated that pretreatment with RA markedly inhibited the expression of IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and Caspase-3 in CCl4-treated hepatocytes. Additionally, RA pretreatment significantly decreased the elevation of mitochondrial membrane potential in CCl4-treated hepatocytes. RA exerted a protective effect against CCl4-induced liver injury in mice through activating Nrf2 signaling pathway, reducing antioxidant damage, suppressing inflammatory response, and inhibiting hepatocyte apoptosis. RA could attenuate BRL hepatocyte ROS production, DNA oxidative damage, inflammatory response, and apoptosis induced by CCl4 exposure.

The Protective Effect of Rheum Ribes L., and Quercetin on Protein Carbonyl Levels Against Carbon Tetrachloride-Induced Liver and Kidney Damage in the Rats

Objective: This study was designed to examine the potential protective effects of Rheum ribes L., and quercetin on protein carbonyl (PCO) in kidney and liver tissue, trace elements (Fe, Cu, Zn) and mineral (P) in serum samples in Wistar rats of carbon tetrachloride (CCl4)-induced oxidative damage. 
 Methods: The 2, 4-dinitrophenylhydrazine (DNPH) method is the most reliable method widely used to measure carbonyl levels in proteins. In this study, the effect of Rheum ribes L. (Rr) and quercetin on protein carbonyl, trace elements (Fe, Cu, Zn) and mineral (P) levels against carbon tetrachloride (CCl4) mediated liver and kidney damage was investigated. For this purpose, 56 Wistar albino female rats weighing 200 ± 220 g were used. Groups were designed as: controls, 0.3 ml DMSO, 1 ml/kg olive oil, 1 ml/kg CCl4, 100 mg/kg Rr, 100 mg/kg quercetin, 100 mg/kg Rr+1 ml/kg CCl4 and 100 mg/kg quercetin+1 ml/kg CCl4 groups. 
 Results: The results showed that the CCl4 group had significantly higher level of protein carbonyl (PCO) than the control, DMSO, olive oil, Rr and quercetin groups (p

Hepatoprotective Effect of Methanol Stem Bark Extract of Diospyros mespiliformis against Carbon Tetrachloride Induced Liver Damage

Aim: This study evaluated the hepatoprotective effects of methanol stem bark extract of Diospyros mespiliformis against carbon tetrachloride-induced liver damage in albino rats.
 Methodology: Acute toxicity study was determined using limit fixed dose test of 5000mg/kg for 14 days. Six (6) adult albino rats of both sexes were used and randomly divided into six groups of one rat each. Hepatoprotective study; a total of forty two (42) adult albino rats were divided in to seven groups, of six rats each. Methanol stem bark extract of Diospyros mespiliformis administered to different groups of rats at the doses of 50 mg/kg, 100 mg/kg, 150 mg/kg and 200 mg/kg orally daily for fourteen. This was followed by CCl4-administration after every 72 hours for the same period. Silymarin a standard reference drug was administered at a dose of 100mg/kg body weight orally, once daily for fourteen (14) days. Hepatoprotective effect was studied by assaying the activities of liver function indices (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transferase, total protein, albumin, direct and total bilirubin) in serum.
 Results: The LD50 of methanol stem bark extract of Diospyros mespiliformis was greater than 5000 mg/kg. The activities of all the marker enzymes revealed a significant (P<0.05) elevated levels and decreased in the levels of total protein and albumin in CCl4 treated rats. Group administered with the extract prior to CCl4 induction show significantly low level of serum liver marker enzymes and increased levels of total protein and albumin compared to CCl4-induced untreated group and this observations is supported by the histology of liver sections, the result indicate that methanol stem bark extract of Diospyros mespiliformis possess significant hepatoprotective property by inhibiting lipid peroxidation.
 Conclusion: This property may be attributed to the phytochemical compounds present in the extract.

Protective effect of Alchornea cordifilia leaf extract on carbon tetrachloride-induced liver damage in Wistar rats

The effect of aqueous extract of the leaves of Alchornea cordifolia on Carbon tetrachloride (CCl4)-induced liver damage was investigated in experimental rats. Treatment of separate groups of rats with 100mg/kg, 150mg/kg and 200mg/kg aqueous leaf extracts of Alchornea cordifolia for 2 weeks after establishment of CCl4 induced liver damage, resulted in significantly (P<0.05) less hepatotoxicity when compared to the CCl4-induced group, as measured by serum alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. The effect of extract was statistically significant (P<0.05) and was dose dependent. Histopathological study also showed significant reduction and even reversal of liver damage in the rats. The results of this study show that aqueous leaf extract of Alchornea cordifolia has a potent anti-hepatotoxic action against CCl4 induced liver damage in rats.

Protective effect of Alchornea cordifilia leaf extract on carbon tetrachloride-induced liver damage in Wistar rats

Protective effect of Alchornea cordifilia leaf extract on carbon tetrachloride-induced liver damage in Wistar rats

Anti-oxidative Effects of Butanol Seed Extract of Parkinsonia aculeata on Carbon Tetrachloride-Induced Liver Damage on Wistar Rats

Medicinal plants have protective effect because of the presence of several compounds which have different mechanism of action. This study sought to assess the anti-oxidative effects of butanol seed extract of Parkinsonia aculeata on carbon tetrachloride (CCl4)-induced liver damage on Wistar rats. The Wistar rats were put into five groups, each with six rats: Group A received a daily dosage of liquid paraffin (1ml/kg); Group B received 1ml/kg body weight of CCl4 (30% in liquid paraffin intraperitoneal); Group C, D, and E received the seed extracts at 100, 120, and 160 mg/kg every day for two weeks. Induction of CCl4 was three times a week for two weeks simultaneously with the extract to the last day. After sacrificed, the liver was harvested and homogenized, and used for further analyses. There was a significant increase (p<0.05) in the levels of superoxide dismutase and catalase in all extract treated groups compared to positive control, except the catalase levels of group treated with 160mg/kg. Similar results was observed in vitamin C, vitamin E and glutathione in rats treated with 100 and 120mg/kg of the extract. The results of this study revealed that butanol seed extract from P. aculeata has antioxidant properties and can protect Wistar rats' livers from the damaging effects of CCl4.

Saffron and saffron ingredients like safranal and crocin’s cytoprotective effects on carbon tetrachloride induced liver damage

Saffron and saffron ingredients like safranal and crocin’s cytoprotective effects on carbon tetrachloride induced liver damage

Hepatoprotective Effects of Vernonia amygdalina (Astereaceae) Extract on CCl4-Induced Liver Injury in Broiler Chickens.

Simple SummarySince the ban on the use of antibiotics as growth promoters in poultry feed, many studies have focused on the use of plants in poultry feed as an alternative to this ban. Currently, many plants are used to improve the growth performance and health status of poultry. Few studies are conducted to evaluate the hepatoprotective effects of these plants in poultry. The current study showed that Vernonia amygdalina extract confers a hepatoprotective effect on poultry. The aim of this study was to evaluate the effect of Vernonia amygdalina leaf extract (VALE) on the carbon tetrachloride-induced hepatotoxicity (CCl4) in broiler chickens. A total of 360-day-old broilers were divided into 4 treatments of 90 birds each consisting of 6 replicates of 15 birds each. The treatments were birds offered 1 mL/kg BW saline (control group), 100 mg/kg BW VALE, 1 mL/kg BW CCl4 (CCl4-treated group), and 100 mg/kg BW VALE + 1 mL/kg BW CCl4 (VALE + CCl4 group). Blood samples were collected at 42 days of age and analyzed for the liver enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and selected biochemical parameters. The experiment was laid out in a completely randomized design. The results obtained showed that VALE had the potential to mitigate the adverse effects of CCl4 on protein and lipid metabolism as reflected in the low serum malondialdehyde (MDA) levels, which is a marker of lipid peroxidation. The aqueous extract of Vernonia amygdalina (VA) at a dose of 100 mg/kg body weight showed a moderate hepatoprotective effect by reducing serum AST levels (p < 0.05). The levels of serum AST, ALP, ALT, and GGT were significantly increased in CCl4-treated birds compared to the control group, reflecting carbon tetrachloride-induced liver damage. The VALE + CCl4 group showed a significantly higher amount of ALP compared to birds treated with carbon tetrachloride, suggesting a hepatoprotective effect. To conclude, Vernonia amygdalina aqueous extract can be used to confer protection against hepatotoxicity, which can induce severe hepatocellular damage in birds.

Protective effects of cerium oxide nanoparticles in non-alcoholic fatty liver disease (NAFLD) and carbon tetrachloride-induced liver damage in rats: Study on intestine and liver

Background and aimsNanoparticles could represent a therapeutic approach for the treatment of various diseases. It has been reported that cerium oxide nanoparticles (CeO2 NPs) have potential useful effects. Therefore, we aimed to examine the protective effects of the CeO2 NPs in two models of liver injury, non-alcoholic fatty liver disease (NAFLD) and carbon tetrachloride (CCl4)-induced liver fibrosis, in rats. MethodsIn this experimental study, male rats were randomly divided into different experimental groups including: Experiment 1; group1: healthy rats received normal saline, 2: CCl4 group, 3: CCl4 + nanoparticle. Experiment 2; group1: healthy rats received chow diet, 2: NAFLD group, 3: NAFLD + nanoparticle. The oxidative stress markers were determined in the liver and intestine. Tumor necrosis factor-α (TNF-α) levels were measured by ELISA. Histopathological changes of liver and intestine were evaluated by light microspore. ResultsTotal antioxidant capacity (TAC) and glutathione (GSH) levels significantly decreased, while malondialdehyde (MDA) and total oxidant status (TOS) were significantly increased in the liver, and intestine of the NAFLD and CCl4 group compared with control rats. However, the use of nanoparticles significantly normalized these markers. The levels of the TNF-α were significantly reduced in the nanoparticle group as compared with NAFLD model and CCl4-treated rats. CeO2 NPs also normalized the liver and intestinal histological changes. ConclusionsOur finding revealed that CeO2 NPs has potential protective effects by increasing antioxidant activity, and reducing inflammation.

Protective Effect of the Mixture of Stem bark, Leaf and Root Extract of Bauhinia acuminata L. against Carbon tetrachloride induced Liver Damage in Wistar Albino Rats

Objective: The objective of the present study was to evaluate the hepatoprotective effect of mixture of stem bark, leaf and root extract of Bauhinia acuminata L. using carbon tetrachloride induced hepatotoxicity model. Method: Powdered mixture materials were extracted with distilled water using soxhlet apparatus. The dried extracts were subjected to preliminary phytochemical analysis and the extracts were evaluated for acute oral toxicity by OECD guidelines 423.The aqueous extract at a dose level 200 mg/kg and 400 mg/kg were selected and administered to albino rats for hepatoprotective screening. Hepatotoxicity was induced by Carbon tetrachloride (1 ml/kg with CMC). Silymarin (100 mg/kg p. o) was used as the standard. Result: The preliminary phytochemical examination showed the presence of Alkaloids, Glycosides, Saponins, Flavanoids, Tannins, Aminoacids, Tryptophan, Quinones, Terpinoids, Starch, Vitamin C and Carbohydrates. Furthermore, the acute toxicity study results showed that the extracts were found to be safe up to 2000 mg/kg b. wt. The extract dose dependently shows hepatoprotective potential by restoring the elevated biochemical parameters. Conclusion: The results obtained from the study indicates that mixture of stem bark, leaves and root extract of Bauhinia acuminata L. possess promising hepatoprotective activity. The activity might be due the presence of the phytoconstituents including Alkaloids, Glycosides, Saponins, Flavanoids, Tannins, Aminoacids, Carbohydrates Terpinoids, Starch, Vitamin C, Tryptophan and Quinones in the extract. Further studies are required to identify the active principle responsible for the hepatoprotective activity.

In vivo and in vitro hepatoprotective effect of three endemic plants against carbon tetrachloride-induced liver damage in rats

Abstract The aim of the study was to investigate in vitro potential antioxidant and hepatoprotective effects of methanolic extracts from the aerial parts of Matricaria pubescens, Centaurea incana, and Santolina africana, against carbon tetrachloride induced liver damage in rats. The different aerial parts of three methanolic extracts, exhibited antioxidant activity in the DPPH free radical (IC50, 0.032, 0.087 and 0.044 mg/ml) respectively. The reducing ability of the extracts showed a dose-dependent trend increasing with increase in the concentrations of the extracts.The antioxidant activity of samples at the concentration of 2 mg/ml was reflected in their ability to inhibit the bleaching of β-carotene. Treated groups with extracts of studied three plants showed decrease in plasma levels of AST, ALT, ALP, and an increase in plasma catalase levels activities, while hepatic MDA decreased and catalase increased as compared to carbon tetrachloride treated groups. In consistency with in vivo and in vitro results, extracts of all three plants ameliorated the carbon tetrachloride extensive damage to liver tissue of treated animals, but, Santolina africana extract was the most efficient.

Synergistic effect of ursolic acid and piperine in CCl4 induced hepatotoxicity

Background Ursolic acid (UA) is a potent plant-based hepatoprotective agent having poor bioavailability, which hampers its therapeutic efficacy. The present study tries to overcome this limitation by combining it with piperine (PIP), a proven bioenhancer and hepatoprotective agent. Methods The type of interaction (synergism, addition, or antagonism) resulting between UA and PIP was analyzed and quantified by isobologram and combination index analysis. The hepatoprotective activity of UA and PIP was evaluated by measuring the level of hepatic marker enzymes. Pharmacokinetic analysis was carried out to ascertain the improvement of bioavailability. Results The combinations significantly decrease the enzyme levels, which indicate better hepatoprotective activity compared to single drugs. The relative oral bioavailability of UA was increased about tenfold (from AUC0– t =12.78 ± 2.59 µg/h/ml to 125.15 ± 1.84 µg/h/ml) along with the improvement of plasma concentration and elimination half-life. Conclusions The findings indicated that the combination of PIP and UA is an effective strategy in enhancing the bioavailability and hepatoprotective potential of UA. KEY MESSAGES Ursolic acid in a combination with piperine provides a synergistic hepatoprotective effect in carbon tetrachloride induced liver damage in rats. Piperine improves the pharmacokinetic properties of ursolic acid when given in combination. Piperine improves the relative oral bioavailability of ursolic acid by tenfold when combined together.

Comparing distress of mouse models for liver damage

In order to foster animal welfare as well as high quality of research, many countries regulate by law that the severity of animal experiments must be evaluated and considered when performing biomedical research. It is well accepted that multiple parameters rather than a single readout parameter should be applied to describe animal distress or suffering. However, since the performance of readout parameters for animal distress is rarely defined and methods for multivariate analysis have only in rare cases been used, it is not known which methodology is most appropriate to define animal distress. This study used receiver operating characteristic curve analysis to quantify the performance of burrowing activity, body weight change and a distress score of mice after induction of liver damage by bile duct ligation or carbon tetrachloride. In addition, Support Vector Machine classification was used to compare the distress of these mouse models. This approach demonstrated that bile duct ligation causes much more distress than carbon tetrachloride-induced liver damage. This study, therefore, provides a prototype how to compare two animal models by considering several readout parameters. In the future these or similar methods for multivariate analysis will be necessary, when assessing and comparing the severity of animal models.

Hepatoprotection by Traditional Essence of Ginseng against Carbon Tetrachloride-Induced Liver Damage.

The peroxide produced in the lipid metabolic process attacks liver cells and causes liver injury. Ginsenosides have been shown to have anti-oxidation abilities and to mend myocardial damage. This study evaluated the effect of traditional ginseng essence (TEG) in preventing chemical liver damage induced by carbon tetrachloride (CCl4). Forty 8-week-old male Sprague Dawley (SD) rats were divided into five groups: control, liver injury (CCl4), and TEG by oral gavage at 0.074, 0.149, or 0.298 g/kg/day for nine weeks. Liver injury biochemical indicators, antioxidant enzyme activity, and lipid contents in liver tissues were evaluated. The liver appearance was observed, and histopathological tests were conducted to estimate whether TEG-antagonized oxidants further ameliorated liver injury. The results show that, after supplementation of TEG for nine consecutive weeks and CCl4—induced liver injury for eight weeks, the levels of liver injury biochemical indicators in animal serum decreased significantly, and, in liver tissue, antioxidant activity was significantly improved and accumulation of lipids was decreased. Pathological sections exhibited reduced liver lipid accumulation and fibrosis. As discussed above, TEG can increase the antioxidant capacity in the liver and the maintenance of hepatocyte function, protecting the liver from chemical injury and improving healthcare.