Carbon Tetrachloride-induced Hepatotoxicity In Rats 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.

Hepatoprotective and in vivo antioxidant effects of granulometric classes and decoction of Ficus dicranostyla Mildbread leaves powders against carbon tetrachloride-induced hepatotoxicity in Wistar rats.

Ficus dicranostyla is a plant from the Moraceae family commonly used in African countries for its nutritional value and its believed medicinal properties. Its antioxidant in vitro capacity and its richness in phenolic compounds have been previously demonstrated. This work aimed at evaluating the hepatoprotective and in vivo antioxidant activities of different granulometric fractions of the F. dicranostyla leaves against carbon tetrachloride-induced hepatotoxicity in rats. Powdery fractions (<125, 250-125, and ≥250 μm), and the unsieved powder, obtained from the F. dicranostyla leaves were water-dissolved and given orally to rats at the same dose (250 mg/kg body weight) before administering carbon tetrachloride intraperitoneally (1 mL/Kg bw). The lipid status parameters (total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol), hepatic toxicity through aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in blood plasma, and antioxidant status by measuring the malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in liver homogenate were performed. The activities of all parameters registered a significant (p < .05) alteration in CCl4-treated rats, which were significantly recovered toward an almost normal level in coadministered with Ficus dicranostyla leaf powder samples in a particle size-dependent manner. Results suggest that the smaller particle size of the powder fraction, as well as the decoction powder of Ficus dicranostyla, may be used as hepatoprotective and antioxidant agents.

Ameliorating Potential of Marketed Formulations Containing Prebiotics And Probiotics Against Carbon Tetrachloride-Induced Hepatotoxicity in rats

In the present work, two marketed formulations VELGUT® (combination of prebiotic and probiotics) and VIZYLAC® (probiotic only) were assessed for a protective effect against carbon tetrachloride-induced chronic liver injury model in rats. Rats were randomly divided into four groups. Normal Control (treated with normal saline) and CCl4 treated group (treated with 1 ml/kg intraperitoneal injection of CCl4 once daily for 10 days followed by twice a week up to 49 days). Test groups composed of the oral treatment of VELGUT (1 mg kg-1) along with CCl4 (T1) and oral treatment of VIZYLAC (4 mg kg-1) along with CCl4. CCl4 treatment in the test group was similar to group 2. At the end of the treatment, various serum biochemical parameters like Alanine aminotransferase (ALT), Aspartate Aminotransferase, (AST), Alkaline Phosphatase (ALP), direct bilirubin, total protein, and albumin levels were measured. Serum cholesterol, glucose and malondialdehyde (MDA) levels were also measured. A small piece of the liver was collected to perform histopathological studies. Serum AST, ALT, ALP, and direct bilirubin were found to be significantly lower as compared to CCl4 intoxicated rats. The level of total protein and albumin was improved. The level of MDA, glucose and cholesterol was improved as compared to CCl4 treated group.

Antioxidant, Anti-inflammatory and hepatoprotective activities of Persicaria maculosa (linn.) and its active principle i.e tannic acid against Carbon tetrachloride induced oxidative stress and hepatotoxicity in wistar rats

Persicaria maculosa (linn.) contains antibacterial, anti-inflammatory, and antioxidant activities, although its protective effects in liver cells are debatable. The effect of Persicaria maculosa (PM) and its active principle, tannic acid (TA), aqueous extracts on carbon tetrachloride-induced hepatotoxicity in rats was investigated in this work. Forty-two male Wistar rats were divided into seven groups: group-I act as Normal group), group-II (Toxicant group CCl 1.5ml/kg i.p), group-III Standard group which pre-treated with silymarin (100mg/kg/day), groups-IV &amp; V which were pretreated with PM aqueous extracts at a dosage of 200 &amp; 400 mg/kg/day o.p, followed by CCl groups-VI &amp; VII which were pretreated with aqueous extracts of TA at doses of 200 &amp; 400 mg/kg/day o.p followed by CClrespectively. After 14 days, liver enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), bilirubin (BIL), and also oxidative stress biomarkers including lipid peroxidation (LPO), in vitro antioxidant activity were measured by 2,2′- diphenyl-1-picrylhydrazyl DPMH. Quantitative determination of some vital phytochemicals, and the histopathological changes were determined using standard procedure. The findings showed that CCl caused a remarkable rise in levels of serum hepatic enzymes such as ALT, AST, ALP and BIL (P≤0.001) compared with the control group. In addition, CCl led to the increasing of LPO (P≤0.001) in liver tissue in comparison with the control group. Rats pretreated with silymarin significantly reduced the adverse effects of CCl on serum and tissue markers. In this regard, remarkable vascular congestion, hepatocellular degeneration, and vacuolization were observed in hepatic tissue of CCl-treated rats. The pre-treatment of Persicaria maculosa and tannic acid aqueous extracts shows a significant improvement was observed in the functional and oxidative stress indices of hepatic tissue alongside histopathology changes.The current investigation found that Persicaria maculosa and its active ingredient Tannic acid aqueous extracts may help to reduce hepatic oxidative injury in rats exposed to CCl by enhancing the oxidant/antioxidant balance.

Ameliorative effect of ethanolic extract of Limnophila rugosa (Scrophulariaceae) in paracetamol- and carbon tetrachloride-induced hepatotoxicity in rats

BackgroundLimnophila rugosa (Scrophulariaceae) is a perennial aquatic plant used as a diuretic and digestive tonic as well as in the treatment of diarrhea, dysentery, dyspepsia and urinary ailments. Genus Limnophila has been reported as hepatoprotective. The present study was undertaken to evaluate the hepatoprotective activity of the ethanolic extract of L. rugosa aerial part in paracetamol- and carbon tetrachloride-induced (CCl4) hepatotoxicity in albino Wistar rats. Ethanolic extract was subjected to high-performance liquid chromatography (HPLC) analysis for the estimation of phenolic and flavonoid compounds and gas chromatography–mass spectrometry (GC–MS) analysis for phytochemical analysis. The in vitro antioxidant activity was carried out by 2,2-diphenyl-1-picrylhydrazyl, nitric oxide radical and hydrogen peroxide assay. Hepatoprotective potential of L. rugosa was studied in paracetamol (750 mg/mg)- and CCl4 (1.25 ml/kg)-induced liver damage in albino rats at dose 200 and 300 mg/kg using silymarin (100 mg/kg) as standard. Lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were determined in liver tissue homogenate. Serum biochemical and histopathological examination was performed. Molecular docking analysis was performed to understand the molecular mechanism of hepatoprotective activity.ResultsHPLC analysis revealed predominance of rutin. GC–MS analysis revealed camphor as principal component. Ethanolic extract exhibited significant concentration-dependent scavenging efficacy. The altered biochemical chemical parameters: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, albumin, globulin and total protein, were significantly improved at 200 and 300 mg/kg in experimental rats. Extract signified hepatoprotective by decreasing lipid peroxidation and upregulating SOD, CAT and GSH. The findings were well supported by histological analysis. 2-Butyl-2, 7-octadien-1-ol (-5.8) and camphor (-4.8) gave the highest docking score on the transforming growth factor-β1.ConclusionsThe ameliorative effect of L. rugosa in the rat model of hepatotoxicity could be attributed to its antioxidant potential and bioactive principles such as betulin, 5-hydroxy-6,7,4′-trimethoxyflavone (salvigenin), betulinic acid, ursolic acid, 3-octanol, acetophenone, anisylacetone, caryophyllene, cis-anethole and the compounds camphor and 2-butyl-2,7-octadien-1-ol identified from GC–MS analysis.

Hepatoprotective and Antioxidant Capacity of Clerodendrum paniculatum Flower Extracts against Carbon Tetrachloride-Induced Hepatotoxicity in Rats.

The aim of the presented work involves the isolation, characterization, and evaluation of hepatoprotective potential of Clerodendrum paniculatum flower extracts. For this purpose, petroleum ether, chloroform, ethyl acetate, alcohol, and water extracts of C. paniculatum flower were screened for the flavonoid and phenolic content and quantified. Various antioxidant activity assays including 2,2′-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) radical scavenging, 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing ability were carried out. Of the above methods, the alcoholic extract exhibited high antioxidant potential and was selected further for the hepatoprotective evaluations. Hepatoprotective evaluation of the alcoholic extract was carried out for carbon tetrachloride (CCl4)-intoxicated model systems. Enzymes associated with liver functions were estimated, and histopathological evaluations were carried out to monitor the liver architecture. Prominently, reduced levels of various associated enzymes along with increased protein content were observed when the liver specimen was pretreated with the extract. Moreover, the liver architecture was almost comparable to that of the normal control group. The column chromatographic analysis of the extract revealed 13 fractions to possess high phenolics and flavonoid contents. The best two fractions were identified for in vitro hepatoprotective evaluation in the goat liver model. Furthermore, the GC–MS analyses of the fractions were carried out followed by a library search, to identify the constituents responsible for the hepatoprotective activity which revealed the presence of four major constituents—pilocarpine, glyceric acid, pangamic acid, and gallic acid. An in vitro hepatoprotective study of the isolated fractions showed better activity compared to the whole alcoholic extract, and the results were comparable to the normal group taken as a control. The investigations with an in vitro model suggest that the isolated fraction with rich flavonoid content showed better hepatoprotective activity. GC–MS analysis of the fractions that displayed good hepatoprotective activity suggested the presence of pilocarpine, glyceric acid, pangamic acid, and gallic acid, while HPTLC analysis revealed the presence of quercetin.

Evaluation of Anti-inflammatory and Antioxidant Effects of Sumatriptan on Carbon Tetrachloride-induced Hepatotoxicity in Rats.

The liver detoxifies and metabolizes many drugs and xenobiotics which may cause hepatotoxicity due to some toxic agents. Carbon tetrachloride (CCl4) is metabolized in cytochrome P450 and its reactive radical metabolites cause lipid peroxidation, cellular injury, and apoptosis. Sumatriptan (SUM), 5-HT1B/1D receptor agonist, had anti-inflammatory and anti-oxidant effects. In this research the effect of SUM pre-treatment against CCl4-induced hepatotoxicity was examined. Adult rats received SUM (0.1, 0.3 and 1 mg/kg; i.p.) for 3 consecutive days before CCl4 (2 ml/kg; i.p. on the 3rd day). The aminotransferases serum levels, tissue levels of anti-oxidant and pro-inflammatory markers and histopathological examination were evaluated. SUM (0.3 mg/kg) prevented significantly the elevation of aminotransferases versus the control group (CCl4 group) (P<0.0001) and also, reversed meaningfully the changes of the MPO, MDA, SOD and CAT, IL-1β and TNF-α levels. Additionally, CCl4-intoxication resulted to the disruption of lobular and cellular structures and inflammation in histopathological evaluation which is prevented by SUM (0.3 mg/kg). These data revealed that SUM (0.3 mg/kg), but no at doses 0.1 and 1 mg/kg, decreases the hepatotoxicity of induced by CCl4 in rats.

Therapeutic effect of dithiophenolato chitosan nanocomposites against carbon tetrachloride-induced hepatotoxicity in rats.

Our previous study showed that dithiophenolate (DTP) and its chitosan nanoparticles (DTP-CSNPs) have abilities to bind with DNA helixes. So in this study, their lethal doses (LD50) and therapeutic roles against rat liver injuries induced by carbon tetrachloride (CCl4) were evaluated. The study focused on the determination of the markers of oxidative stress (OS) and apoptosis and compare the results with those of cisplatin treatment. The results revealed that LD50 values of DTP and DTP-CSNPs are 2187.5 and 1462.5 mg/kg, respectively. Treatment with DPT and DPT-CSNPs after CCl4 administration reduced liver injuries, induced by CCl4, and improved liver functions and architecture through the reduction of OS and apoptosis. Where the oxidant marker was decreased with elevations of antioxidant markers. Also, there was an elevation in Bcl-2 value, with decreases in caspase-8, Bax, and Bax/Bcl-2 ratio. DPT-CSNPs treatment gave preferable results than those treated with DPT. Moreover, DTP and DPT-CSNPs treatment gave better results than cisplatin treatment. The administration of healthy rats with low doses of DTP and DTP-CSNPs for 14 days had no effect. Otherwise, the study on HepG2 cell line showed that DTP and DPT-CSNPs inhibited cell growth by arresting cells in the G2/M phase and inducing cell death. In conclusion, DTP and DTP-CSNPs have antiapoptotic and anti-oxidative stress toward hepatotoxicity induced by CCl4. Moreover, DTP and DTP-CSNPs have anticancer activity against the HepG2 cell line. Generally, DTP-CSNPs are more effective than DTP. So, they can be used in the pharmacological fields, especially DTP-CSNPs.

Pharmacognostic Profile, In-vitro Antioxidant and Hepatoprotective Potential of Ethanolic Fruit Extract of Pyrus communis Linn.

Background: The Ethanolic Extract of Pyrus communis L. fruit (EEPC) was assessed for hepatoprotective and in vitro antiradical activity against carbon tetrachloride-induced hepatotoxicity in rat’s liver. Methods: The degree of hepatoprotection was screened by measuring biochemical parameters, including serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP), Total Albumin (TA), Total Protein (TP) and Total Bilirubin (TB). The antiradical activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide and nitric oxide free radical scavenging property. The hepatoprotective effects of the extract were compared with Silymarin used as a standard drug (100 mg/kg, p.o, bodyweight). Results: The ethanolic extract of the fruit has the capabilities to scavenge free radicals, in vitro, respectively. Additionally, the ethanolic extract (200 mg/kg and 400 mg/kg, p.o, bodyweight) exhibited marked hepatoprotective action regarding CCl4 intoxicated rodents in a dose-dependent manner. EEPC at a dose of 400mg/kg could afford significant dose-dependent protection against CCl4 induced hepatocellular injury. Conclusion: Biochemical samples obtained from the animals treated with ethanolic extracts (400mg/kg, body weight) showed a significant decrease in the levels of serum markers indicating hepatic cell protection.

Govaniadine Ameliorates Oxidative Stress, Inflammation, and Kupffer Cell Activation in Carbon Tetrachloride-Induced Hepatotoxicity in Rats.

Liver diseases such as hepatic carcinoma are one of the main health problems worldwide. Herbal drugs are largely used to treat liver injury in the indigenous system of medicine and may provide lead compounds for hepatoprotective drug discovery. The present study is investigated to test the Corydalis govaniana Wall. extract, fraction, and isolate therapeutically active constituents to explore their hepatoprotective, anti-inflammatory, and antioxidant activities. For this purpose, the antioxidant activity of govaniadine, caseadine, caseamine, and protopine was performed by assessing the scavenging events of the stable 2,2-diphenyl-1-picrylhydrazyl. Hepatoprotection of govaniadine was assessed in terms of reduction in serum enzymes (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) caused by CCl4-induced liver injury in rats and by histopathological techniques. All the compounds showed significant antioxidant activity with a percentage inhibition of 92.2, 86.7, 85.3, and 79.7, respectively, compared to propyl gallate 90.3%. Treatment with govaniadine reduced the serum enzyme level down to normal levels in the CCl4-treated group while inhibiting the increase of malondialdehyde, and the induction of superoxide dismutase and the glutathione level was upregulated. Histopathology showed ∼47% damage to the liver cells in the CCl4-treated group; reduction in this damaged area was found to be better upon using govaniadine. Immunohistochemistry results showed that govaniadine as compared to silymarin has exceedingly decreased the inflammation by halting the CCl4-induced activation of hepatic macrophages. In carrageenan-induced paw edema assay, govaniadine significantly alleviated the edema after 1–5 h at a dose of 20 mg/kg (26.00 and 28.5%), 50 mg/kg (22.05 and 27.0%), and 100 mg/kg (20.02 and 25.30%), respectively. The results of our experiments suggest that govaniadine showed antioxidant and hepatoprotective activity in liver injury. The hepatoprotective function of govaniadine may be associated to the scavenging of the free radical and attenuation of oxidative stress as well as inflammatory responses in the liver. Hence, govaniadine may be a lead compound for the hepatoprotective drug discovery process and further research is needed to find out their molecular mechanism of protection.

Hepatoprotective Activity of Cassia Auriculata against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

In previous decade the herbal drugs have been investigated for their medicinal properties for the natural therapy. About half of the people around the world, even in the developed countries had been using the medicinal plants and natural drugs as treatment of diseases. In this regard the herbs should also be investigated for their pharmacological properties, safety concerns and efficacy too. In the present investigation, we have believed medicine and inhibiting potential effects of extract of C. auriculata was investigated for the hepatoprotective activity. This study facilitated to rediscover the new ancient medication for the treatment of liver diseases. The plant C.auriculata showed very good activity in terms of the hepatoprotective nature against the liver injury by chornic use of drugs which is due to the anti-inflammatory properties added to the antioxidant activity of the herbs. These were to prevent the CCl4 induced free radicals and damage. The formation of cellular damage and free radicals was inhibited. The data that we procured from the investigation shows that the antioxidant activity of the plant in both extracts of plant helped for the activity. It may contain large amounts of the phenols and flavonoids that showed free radial scavenging activity which might be responsible for the hepatoprotective activity also.

Isolation and biological activities of naturally occurring apocarotenoid bixin

The naturally occurring apo-carotenoid bixin is obtained from annatto (Bixa orellana). It is unique among the natural carotenoids through its water solubility and easily extractability from the seed coat of Bixa orellana. Bixin is (2E,4E,6E,8E,10E,12E,14E,16Z, 18E)-20- methoxy-4,8,13,17-tetramethyl-20-oxicosa 2,4,6,8,10,12,14,16,18-nonaenoic acid, an apo-carotenoid which is a terpenoid compound derived from the oxidative cleavage of carotenoids. Several biological activities of bixin has been reported earlier such as selective antimyeloma effects of cis-bixin, antinociceptive and anti-Inflammatory effects, antioxidant action against cis-platine induced chromosome in rats, hypoglycemic effect in alloxan-induced diabetic rats, allodynia, anxious and depressive-like behaviors, targeting NRF2 for improved skin barrier function and photoprotection, antiatherogenic effect in hypercholesterolemic rabbits, triggering apoptosis of cancer cells, immunomodulatory role in dogs, sensitization of human melanoma cells to dacarbazine-induced apoptosis, sensitization of human lung cancer and cervical cancer cell to cisplatin in vitro, anti-SARS-CoV-2 activity, antibacterial activity of cis-bixin conjugated silver nanoparticles, protective effect on carbon tetrachloride-induced hepatotoxicity in rats, bixin/crocetin nanoparticles on quality and shelf life improvement of cheddar cheese etc. In this review, the biological properties of bixin has been discussed. A practical method for the isolation of bixin 1 from the seed coat of Bixa orellana commonly known as “Sinduri” (in Bengali) and its characterization has also been reported.

Pharmacological impact of Agaricus bisporus extract in carbon tetrachloride-induced hepatotoxicity in rats

Drug-induced hepatotoxicity is a frequent cause of liver injury worldwide. The present study was designed to evaluate the possible hepato-protective potential Agaricus bisporus extract (ABE; a type of mushrooms) in albino rats using Carbon tetrachloride (CCl4)-model of liver injury. Forty-two albino rats were utilized in this experiment arranged randomly in seven groups, six rats each, of different treatments. He-patic injury model was induced by administration of CCl4 (25% in corn oil) at a dose of 2.5 ml/kg, interperitoneally, twice weekly for 8 weeks (+ve control); test group rats received ABE at escalating doses of 200 or 400 mg/kg, orally, daily for 8 weeks with exposure to CCl4; standard group rats received Silymarin at dose of 100 mg/kg, orally, daily for 8 weeks along with CCl4; further 2 groups of rats received only ABE at the same dose levels; while rats of -ve control group received only the vehicles of the used drugs. Blood and liver tissue sam-ples were picked out at the end of the experimental course for different assays. Biochemical analysis revealed that ABE exhibited dose-dependent hepatoprotection indicated by almost normalized biomarkers, including, enzymatic liver function parameters, namely, AST, ALT, GGT &amp; ALP with potential % of 93.1, 58.2, 65.2, 68.9, respectively, after ABE large dose when standardized by Silymarin; non-enzymatic parameters, namely, total protein, albumin, globulins, total bilirubin, conjugated bilirubin, unconjugated bilirubin, TAGs, Cholesterol, HDL, LDL &amp; VLDL with potential % of 59.3, 54.5, 57.3, 81.8, 81.0, 80.0, 75.5, 90.4, 80.8, 84.5 &amp; 78.7, respectively, after ABE large dose when standardized by Silymarin. The mechanism of the obtained hepatoprotection of ABE may be based on impeding the oxidative stress mediated by the used hepatotoxin, indicated by reduced MDA (37.9 % of Silymarin), and restored SOD, Catalase &amp; GPx in liver homogenate with potentials of 94.9, 63.0 &amp; 88.4 % of Silymarin, respectively. Pathological findings, both macroscopic and microscopic, were supportive to the biochemical findings, where the pathological lesions caused by CCl4 as fatty degeneration of hepatocytes with vacuolated cytoplasm, proliferated fibrous connective tissue with eosinophilic edematous fluid cells plus focal and diffuse necrotic areas and hyperplastic biliary epithelium, were ameliorated dose-dependently when ABE was administered together with CCl4. Data of the present study may suggest ABE as a good natural source for promising hepatoprotective and antioxidative remedies.

Star Anise (Illicium verum) oil administration alleviates carbon tetrachloride-induced hepatotoxicity in rats

Abstract: The purpose of this work was to evaluate the protective effect of star anise oil against carbon tetrachloride (CCL4)-induced hepatic injury and oxidative stress in rats. Twenty-four male Wistar rats were divided into four equal groups. Group I (control): rats administered corn oil1 ml/kg orally every day for 5 weeks. Group II (star anise oil exposed group): rats received (1 ml/kg orally) every day via gastric tube over a period of 5 weeks. Group III (carbon tetrachloride): rats were injected IP with CCl4 (1:3 in corn oil, 2.5 ml/Kg, 3 doses at 72 hr interval) for 5 weeks. Group IV (CCl4 injected rats plus star anise oil) rats daily received star anise oil (1 ml/kg orally)plus CCl4 (as in group III).Obtained results showed significant increase in serum ALT, AST and ALP activities, decrease in total protein, albumin and globulin concentrations and significant increase liver tissue MDA level in CCL4 exposed rats. In addition , a significant decrease in GSH and CAT concentrations were recorded when compared with control group. Administration of star anise oil with CCL4 induced significant improvement of all previous parameters towards their normal ranges. Various histopathological alterations were detected in the liver treated with CCL4. Interestingly, rats treated with star anise oil plus CCL4 showed marked reduction in these pathological alterations in comparison to CCL4 intoxicated rats. These results suggested that star anise oil has the potential to ameliorate CCL4 induced hepatic damage.

The Effect of Humulus lupulus Extract on Serum Biochemical Parameters in Carbon Tetrachloride-induced Hepatotoxicity in Rats

The Effect of Humulus lupulus Extract on Serum Biochemical Parameters in Carbon Tetrachloride-induced Hepatotoxicity in Rats

Protective Effects of Propolis and Probiotic Lactobacillus acidophilus against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Background: Propolis (PRS) and probiotic bacteria Lactobacillus are natural products used as dietary supplement for their therapeutic benefits. This study was performed to examine the possible hepatoprotective effect of PRS and probiotics (PRCs) against carbon tetrachloride-induced liver injury. Methods: Experimentally, intoxicated rats received 0.5 ml/kg CCl4 (i.p.) daily for six days, pretreated rats received per os PRS 100 mg/kg or PRCs 109 CFU for six days followed by a single dose of 0.5 ml/kg CCl4. Control groups received either PRS, PRCs or olive oil for six days. Then, serum biochemistry (total protein, cholesterol, triglycerides and albumin) and oxidative stress parameters were measured. Results: We showed that CCl4 treatment was associated with an increase of the serum aspartate amino transferase (AST), alanine aminotransferase (ALT), cholesterol and triglycerides levels. In parallel, serum total protein, albumin and blood sugar levels were significantly decreased. Regarding the oxidative stress parameters, catalase and glutathione S-transferase (GST) levels were lower, conversely to the lipid peroxidation (MDA). Conclusion: Our results strongly support that administration of PRS and PRCs may significantly protect liver against CCl4-induced toxicity by enhancing antioxidative stress pathway and preventing lipid peroxidation.

Antioxidant and hepatopreventive effects of Cassia angustifolia extract against carbon tetrachloride-induced hepatotoxicity in rats

The present study aimed to investigate the preventive effects of methanol fraction from Cassia angustifolia leaf extract (MECA), associated with its phytochemical content, on CCl4-induced hepatic toxicity in adult rats. In the controls, CCl4 induced an increase of serum biochemical parameters and triggered oxidative stress in the liver. MECA caused significant reductions in CCl4-elevated levels of hepatic markers, total cholesterol, triglycerides, and low-density lipoprotein and increased the level of high-density lipoprotein compared to the CCl4 group. Moreover, pretreatment with the MECA produced significant reductions in lipid peroxidation (thiobarbituric acid reactive substances) and protein carbonyl level in liver tissues as compared with the untreated group. The formation of pathological hepatic lesions was strongly prevented by MECA. Overall, this study suggests that administration of MECA has a high potential to quench free radicals and alleviate CCl4-induced hepatotoxicity in rats.

PREVENTION EFFECTS OF METHANOLIC EXTRACT OF Eurycoma longifolia ROOTS ON CARBON TETRACHLORIDE-INDUCED HEPATOTOXICY IN RATS

The objective of this study was to investigate preventive effects of methanolic extract of Eurycoma longifolia roots (MEEL) against carbon tetrachloride-induced hepatotoxicity in rats. A total of 25 rats were randomly divided into five groups (n=5). Group I treated with Sodium CMC 1% w/v (peroral, 6 days), group II treated with single dose of CCl 4 in olive oil (1:1) 2 mL/kg (intraperitoneal injection). Groups III-V treated with 75, 150, and 300 mg/kg BW of MEEL (peroral, 6 days) respectively, and administration of CCl 4 in olive oil (1:1) 2 mL/kg (intraperitoneal injection) on seventh day. The hepatoprotective potential was estimated by measuring serum activity of biochemical parameters. Further, liver weight ratio and histopathological changes were determined. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were significantly ( P <0.05) increased and albumin decreased significantly ( P <0.05) in CCl 4 treated group, but treatment with MEEL 75 mg/kg significantly ( P <0.05) prevented the elevation of ALT, AST, and LDH. Histopathological changes also show hepatic protection of MEEL 75 mg/kg. It is suggested that methanolic extract of Eurycoma longifolia roots75 mg/kg would be enough to give a protective effect against CCl 4 -induced hepatotoxicity.

Micellar propolis nanoformulation of high antioxidant and hepatoprotective activity

The present study reports a promising antioxidant protection by a recently developed micellar propolis formulation, against oxidative stress in in vitro and in vivo models of toxicity. The formulation, based on poplar propolis encapsulated in poly(ethylene oxide)–β-poly(propylene oxide)–β-poly(ethylene oxide) triblock copolymer (PEO26–PPO40–PEO26) micelles is characterized by small size (Dh=20nm), enhances aqueous solubility and good colloidal stability. In vitro, propolis-loaded PEO26–PPO40–PEO26 micelles (20–100μg/ml) significantly increased the cell viability of human hepatoma HepG2 cells, subjected to H2O2-induced cell injury (0.1mM, 1h). Antioxidant activity and protection of the micellar propolis were evaluated in a model of carbon tetrachloride-induced hepatotoxicity in rats (10% CCl4 solution, 1.25ml/kg, p.o.) by measurement of non-enzyme (malondialdehyde and glutathione) and enzyme (catalase and superoxide dismutase) biomarkers of oxidative stress. Clinic observations, hematological, biochemical parameters and histological analysis were also performed. In vivo, micellar propolis (20mg/kg b.w., p.o., 14 days) ameliorated CCl4-induced acute liver injury in rats. The oral administration of micellar propolis significantly prevented serum transaminase increases, as well as brought the levels of malondialdehyde, glutathione, and antioxidant enzymes catalase and superoxide dismutase toward the controls levels. Therefore, PEO26–PPO40–PEO26 micelles could be considered as a promising oral delivery system of propolis against oxidative stress injury in liver cells.

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

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