Protective effect of saponins derived from the roots of Platycodon grandiflorum against carbon tetrachloride induced hepatotoxicity in mice

The purpose of this study was to investigate the protective effects of the saponins isolated from the root of Platycodi Radix (Changkil saponins: CKS) on carbon tetrachloride (CCl(4))-induced hepatotoxicities in mice. Pretreatment with CKS prior to the administration of CCl(4) significantly prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activities and hepatic lipid peroxidation formation. In addition, CKS prevented CCl(4)-induced apoptosis and necrosis, as indicated by a liver histopathologic study and DNA laddering. To determine whether Fas/Fas ligand (FasL) pathway involved in CCl(4)-induced acute liver injury, Fas and FasL proteins and caspase-3, -8 activities were tested by western blotting and ELISA. CKS markedly decreased CCl(4)-induced Fas/FasL protein expression levels and in turn attenuated CCl(4)-induced caspase-3, -8 activities in mouse livers. Additionally, CKS protected the CCl(4)-induced depletion of hepatic glutathione levels. The effect of CKS on CYP2E1, the major isozyme involved in CCl(4) bioactivation, was investigated. Treatment with CKS resulted in a significant decrease in the CYP2E1-dependent hydroxylation of aniline. In addition, CKS exhibited antioxidant effects on FeCl(2)-ascorbate induced lipid peroxidation in liver homogenates, and on superoxide radical scavenging activity. These findings suggest that the protective effects of CKS against CCl(4)-induced acute liver injury possibly involve mechanisms related to its ability to block CYP2El-mediated CCl(4) bioactivation and its free radical scavenging effects, and that is also protects against Fas/FasL pathway mediated apoptosis.     

Protective effects of puerarin on carbon tetrachloride-induced hepatotoxicity

Puerarin, the main isoflavone glycoside found in the root of Pueraria lobata, has been used for various medicinal purposes in traditional Chinese medicine for thousands of years. The purpose of this study was to investigate the protective effects of puerarin against hepatotoxicity induced by carbon tetrachloride (CCl4) and the mechanism of its hepatoprotective effect. In mice, pretreatment with puerarin prior to the administration of CCl4 significantly prevented the increased serum enzymatic activity of alanine aspartate aminotransferase and hepatic malondialdehyde formation in a dose-dependent manner. In addition, pretreatment with puerarin significantly prevented both the depletion of reduced glutathione (GSH) content and the decrease in glutathione S-transferase (GST) activity in the liver of CCl4-intoxicated mice. Hepatic GSH levels and GST activity were increased by treatment with puerarin alone. CCl4-induced hepatotoxicity was also prevented, as indicated by liver histopathology. The effects of puerarin on cytochrome P450 (CYP) 2E1, the major isozyme involved in CCl4 bioactivation, were also investigated. Treatment of the mice with puerarin resulted in a significant decrease in the CYP2E1-dependent aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the CYP2E1 protein levels were also lowered. Puerarin exhibited anti-oxidant effects on FeCl2-ascorbate induced lipid peroxidation in mouse liver homogenates, and on superoxide radical scavenging activity. These results suggest that the protective effects of puerarin against the CCl4-induced hepatotoxicity possibly involve mechanisms related to its ability to block CYP-mediated CCl4 bioactivation, induction of GST activity and free radical scavenging effects.     

Protective effects of kahweol and cafestol against hydrogen peroxide-induced oxidative stress and DNA damage

There is an increasing evidence that oxidative stress is implicated in the processes of inflammation and carcinogenesis. It has been shown that kahweol and cafestol, coffee-specific diterpenes, exhibit chemoprotective effects. This study investigated the effects of kahweol and cafestol, coffee-specific diterpenes, on the hydrogen peroxide (H(2)O(2))-induced oxidative stress and DNA damage in NIH3T3 cells. When the cells were treated with kahweol or cafestol, cytotoxicity, lipid peroxidation, and reactive oxygen species production induced by H(2)O(2) were markedly reduced in a dose-dependent manner. Moreover, kahweol and cafestol were shown to be highly protected against H(2)O(2)-induced oxidative DNA damage as determined by the Comet (single cell gel electrophoresis) assay and the measurement of 8-oxoguanine content in NIH3T3 cells. Kahweol and cafestol also protected hydroxyl radical-induced 2-deoxy-d-ribose degradation by ferric ion-nitrilotriacetic acid and H(2)O(2). In addition, kahweol and cafestol efficiently removed the superoxide anion generated from the xanthine/xanthine oxidase system. These results suggest that kahweol and cafestol are effective in protecting against H(2)O(2)-induced oxidative stress and DNA damage, probably via scavenging free oxygen radicals, and that kahweol and cafestol act as antioxidants.     

Antioxidant and hepatoprotective actions of the medicinal herb Artemisia campestris from the Okinawa Islands

The antioxidant action of Artemisia campestris was examined in vitro and in vivo. A water extract of A. campestris showed a strong scavenging action of 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl and superoxide anion radicals. When the extract was given intraperitoneally to mice prior to carbon tetrachloride (CCl4) treatment, CCl4-induced liver toxicity, as seen by an elevation of serum aspartate aminotransferase and alanine aminotransferase activities, was significantly reduced. Depression of the elevation of serum enzyme levels after CCl4-treatment was also observed by oral administration of the extract. In that case, CCl4-derived lipid peroxidation in the liver was decreased by the extract treatment. These results suggest that the extract of A. campestris scavenges radicals formed by CCl4 treatment resulting in protection against CCl4-induced liver toxicity.     

Protective effect of Platycodi radix on carbon tetrachloride-induced hepatotoxicity.

The protective effects of a Platycodi radix (Changkil: CK), the root of Platycodon grandiflorum A. DC (Campanulaceae) on carbon tetrachloride (CC14)-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with CK prior to the administration of CC14 significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. In addition, pretreatment with CK also significantly prevented the elevation of hepatic malondialdehyde formation and the depletion of reduced glutathione content in the liver of CC14-intoxicated mice. However, hepatic reduced glutathione levels and glutathione S-transferase activities were not affected by treatment with CK alone. CC14-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. The effects of CK on the cytochrome P450 (P450) 2E1, the major isozyme involved in CC14 bioactivation were also investigated. Treatment of mice with CK resulted in a significant decrease of P450 2E1-dependent p-nitrophenol and aniline hydroxylation in a dose-dependent manner. CK showed antioxidant effects in FeCl2-ascorbate-induced lipid peroxidation in mice liver homogenate and in superoxide radical scavenging activity. Our results suggest that the protective effects of CK against CC14-induced hepatotoxicity possibly involve mechanisms related to its ability to block P450-mediated CC14 bioactivation and free radical scavenging effects.     

Saponins isolated from the root of Platycodon grandiflorum protect against acute ethanol-induced hepatotoxicity in mice

The protective effects of saponins isolated from the root of Platycodon grandiflorum (Changkil saponins: CKS) against alcoholic steatosis in liver injury induced by acute ethanol administration were investigated. Pretreatment with CKS prior to ethanol administration significantly prevented the increases in serum alanine aminotransferase activity, hepatic TNF-α level, hepatic lipid peroxidation and hepatic triglyceride level. CKS prevented ethanol-induced steatosis and necrosis, as indicated by liver histopathological studies. Additionally, CKS protected against ethanol-induced depletion of hepatic glutathione levels. CYP2E1 has been suggested as a major contributor to ethanol-induced oxidative stress and liver injury. The concurrent administration of CKS efficaciously abrogated the CYP2E1 induction and CYP2E1-dependents hydroxylation of aniline as compared to the individual treatment at higher doses. These findings suggest that CKS may prevent ethanol-induced acute liver injury, possibly through its ability to block CYP2El-mediated ethanol bioactivation and its free radical scavenging effects.     

Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl(4)-intoxicated mice

This study investigated the protective effects of isoquinoline alkaloid berberine on the CCl(4)-induced hepatotoxicity in mice. Berberine was administered as a single dose at 5 and 10mg/kg intraperitoneally (i.p.), 1h before CCl(4) (10%, v/v in olive oil, 2ml/kg) injection and mice were euthanized 24h later. The rise in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in CCl(4)-intoxicated mice was markedly suppressed by berberine in a concentration-dependent manner. The decrease in hepatic activity of superoxide dismutase (Cu/Zn SOD) and an increase in lipid peroxidation were significantly prevented by berberine. Histopathological changes were reduced and the expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was markedly attenuated by berberine 10mg/mg. The results of this study indicate that berberine could be effective in protecting the liver from acute CCl(4)-induced injury. The hepatoprotective mechanisms of berberine may be related to the free radical scavenging and attenuation of oxidative/nitrosative stress, as well as to the inhibition of inflammatory response in the liver.     

Hepatoprotective effects of 18beta-glycyrrhetinic acid on carbon tetrachloride-induced liver injury: inhibition of cytochrome P450 2E1 expression.

The protective effects of 18beta-glycyrrhetinic acid (GA), the aglycone of glycyrrhizin (GL) derived from licorice, on carbon tetrachloride-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with GA prior to the administration of carbon tetrachloride significantly prevented an increase in serum alanine, aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with GA also significantly prevented the depletion of glutathione (GSH) content in the livers of carbon tetrachloride-intoxicated mice. However, reduced hepatic GSH levels and glutathione-S-transferase activities were unaffected by treatment with GA alone. Carbon tetrachloride-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic study. The effects of GA on the cytochrome P450 (P450) 2E1, the major isozyme involved in carbon tetrachloride bioactivation, were also investigated. Treatment of mice with GA resulted in a significant decrease of the P450 2E1-dependent hydroxylation of p-nitrophenol and aniline in a dose-dependent manner. Consistent with these observations, the P450 2E1 expressions were also decreased, as determined by immunoblot analysis. GA also showed antioxidant effects upon FeCl(2)-ascorbate-induced lipid peroxidation in mice liver homogenate and upon superoxide radical scavenging activity. These results show that protective effects of GA against the carbon tetrachloride-induced hepatotoxicity may be due to its ability to block the bioactivation of carbon tetrachloride, primarily by inhibiting the expression and activity of P450 2E1, and its free radical scavenging effects.     

Mechanism of antihepatotoxic activity of atractylon, I: effect on free radical generation and lipid peroxidation1.

The mechanism of antihepatotoxic action of atractylon, a main sesquiterpenic constituent of ATRACTYLODES rhizomes, was studied. Atractylon inhibited carbon tetrachloride (CCl (4))-induced cytotoxicity in primary cultured rat hepatocytes and CCl (4)-induced lipid peroxidation by rat liver microsomes. However, atractylon increased the free radical generation by CCl (4) with rat liver microsomes in the presence of a radical trapping agent, phenyl T-butyl nitrone (PBN). In addition, atractylon generated free radical PER SE. Experiments using (13)CCl (4) instead of CCl (4) indicated that the increased free radicals consisted of those from (13)CCl (4) and from atractylon. Accumulated data support that although both CCl (4) and atractylon generate free radicals respectively by rat liver microsomes, free radical from CCl (4) conducts lipid peroxidation and produces liver lesion, while atractylon forms free radical which scavenges CCl (3) radical in the absence of PBN, inhibits lipid peroxidation by CCl (4) and suppresses CCl (4)-induced liver lesion.     

Role of cytochrome P4502E1 in retinol's attenuation of carbon tetrachloride-induced hepatotoxicity in the Swiss Webster mouse.

In the mouse, retinol administration attenuates carbon tetrachloride (CCl4)-induced hepatic injury. We have investigated the role of cytochrome P4502E1 (CYP2E1) in this interaction. Male Swiss Webster mice were administered retinol (75 mg/kg/d) or vehicle for 3 days prior to CCl4 (30 microl/kg, ip). Hepatotoxicity produced by CCl4 was assessed by plasma alanine aminotransferase (ALT) activity and light microscopy (ALT activity of 1391+/-430 vs. 274+/-92 IU/L for vehicle + CCl4 and retinol + CCl4 treatments respectively, p < 0.05). Retinol's attenuation of liver injury was maintained when CCl4 was administered 48 h after the conclusion of the retinol pretreatment. Aniline hydroxylation activity, an indicator of CYP2E1 catalytic activity, determined on day 4 was 33.8% of untreated control in vehicle + CCl4 treatments while the retinol + CCl4 treatment group was 94.2% of untreated control. Additionally, CYP2E1 immunoreactive protein was 78% lower in vehicle + CCl4 vs. retinol + CCl4 treatment groups. Attenuation of potentiated hepatotoxicity was also observed when CYP2E1 was induced by acetone (ALT activity of 3119+/-1066 vs. 247+/-77 IU/L for vehicle and retinol treatments respectively, p < 0.05). In the mouse, retinol itself does not alter constitutive or inducible CYP2E1 expression. However, in combination with CCl4 retinol does reduce the amount of CCl4 bioactivated to its toxic metabolite. We conclude that retinol attenuates CCl4-induced hepatotoxicity by causing a decrease in CCl4 bioactivation but does not cause a decrease in CYP2E1 expression.     

Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model

The use of many halogenated alkanes such as carbon tetrachloride (CCl4), chloroform (CHCl3) or iodoform (CHI3), has been banned or severely restricted because of their distinct toxicity. Yet CCl4 continues to provide an important service today as a model substance to elucidate the mechanisms of action of hepatotoxic effects such as fatty degeneration, fibrosis, hepatocellular death, and carcinogenicity. In a matter of dose,exposure time, presence of potentiating agents, or age of the affected organism, regeneration can take place and lead to full recovery from liver damage. CCl4 is activated by cytochrome (CYP)2E1, CYP2B1 or CYP2B2, and possibly CYP3A, to form the trichloromethyl radical, CCl3*. This radical can bind to cellular molecules (nucleic acid, protein, lipid), impairing crucial cellular processes such as lipid metabolism, with the potential outcome of fatty degeneration (steatosis). Adduct formation between CCl3* and DNA is thought to function as initiator of hepatic cancer. This radical can also react with oxygen to form the trichloromethylperoxy radical CCl3OO*, a highly reactive species. CCl3OO* initiates the chain reaction of lipid peroxidation, which attacks and destroys polyunsaturated fatty acids, in particular those associated with phospholipids. This affects the permeabilities of mitochondrial, endoplasmic reticulum, and plasma membranes, resulting in the loss of cellular calcium sequestration and homeostasis, which can contribute heavily to subsequent cell damage. Among the degradation products of fatty acids are reactive aldehydes, especially 4-hydroxynonenal, which bind easily to functional groups of proteins and inhibit important enzyme activities. CCl4 intoxication also leads to hypomethylation of cellular components; in the case of RNA the outcome is thought to be inhibition of protein synthesis, in the case of phospholipids it plays a role in the inhibition of lipoprotein secretion. None of these processes per se is considered the ultimate cause of CCl4-induced cell death; it is by cooperation that they achieve a fatal outcome, provided the toxicant acts in a high single dose, or over longer periods of time at low doses. At the molecular level CCl4 activates tumor necrosis factor (TNF)alpha, nitric oxide (NO), and transforming growth factors (TGF)-alpha and -beta in the cell, processes that appear to direct the cell primarily toward (self-)destruction or fibrosis. TNFalpha pushes toward apoptosis, whereas the TGFs appear to direct toward fibrosis. Interleukin (IL)-6, although induced by TNFalpha, has a clearly antiapoptotic effect, and IL-10 also counteracts TNFalpha action. Thus, both interleukins have the potential to initiate recovery of the CCl4-damaged hepatocyte. Several of the above-mentioned toxication processes can be specifically interrupted with the use of antioxidants and mitogens, respectively, by restoring cellular methylation, or by preserving calcium sequestration. Chemicals that induce cytochromes that metabolize CCl4, or delay tissue regeneration when co-administered with CCl4 will potentiate its toxicity thoroughly, while appropriate CYP450 inhibitors will alleviate much of the toxicity. Oxygen partial pressure can also direct the course of CCl4 hepatotoxicity. Pressures between 5 and 35 mmHg favor lipid peroxidation, whereas absence of oxygen, as well as a partial pressure above 100 mmHg, both prevent lipid peroxidation entirely. Consequently, the location of CCl4-induced damage mirrors the oxygen gradient across the liver lobule. Mixed halogenated methanes and ethanes, found as so-called disinfection byproducts at low concentration in drinking water, elicit symptoms of toxicity very similar to carbon tetrachloride, including carcinogenicity.     

Drinking of Salvia officinalis tea increases CCl(4)-induced hepatotoxicity in mice.

In a previous study, the drinking of a Salvia officinalis tea (prepared as an infusion) for 14 days improved liver antioxidant status in mice and rats where, among other factors, an enhancement of glutathione-S-transferase (GST) activity was observed. Taking in consideration these effects, in the present study the potential protective effects of sage tea drinking against a situation of hepatotoxicity due to free radical formation, such as that caused by carbon tetrachloride (CCl(4)), were evaluated in mice of both genders. Contrary to what was expected, sage tea drinking significantly increased the CCl(4)-induced liver injury, as seen by increased plasma transaminase levels and histology liver damage. In accordance with the previous study, sage tea drinking enhanced significantly GST activity. Additionally, glutathione peroxidase was also significantly increased by sage tea drinking. Since CCl(4) toxicity results from its bioactivation mainly by cytochrome P450 (CYP) 2E1, the expression level of this protein was measured by Western Blot. An increase in CYP 2E1 protein was observed which may explain, at least in part, the potentiation of CCl(4)-induced hepatotoxicity conferred by sage tea drinking. The CCl(4)-induced hepatotoxicity was higher in females than males. In conclusion, our results indicate that, although sage tea did not have toxic effects of its own, herb-drug interactions are possible and may affect the efficacy and safety of concurrent medical therapy with drugs that are metabolized by phase I enzymes.     

Antioxidative effect of chitosan on chronic carbon tetrachloride induced hepatic injury in rats

Carbon tetrachloride (CCl(4)) is a toxic material known to induce lipid peroxidation and liver damage. To determine if chitosan has antioxidative effects on CCl(4)-induced liver injury, we administered 1 ml/kg of CCl(4) resolved in a 50% corn oil solution to rats every week by intraperitoneal injection. Chitosan (200 mg/kg body weight per day, MW 380,000 Da) was administered to the CCl(4) + chitosan treated rats by oral gavage during the experimental period. Chitosan significantly decreased liver thiobarbituric acid reactive substances (TBARS) and increased antioxidant enzyme activities (catalase and superoxide dismutase (SOD)). Fatty acid composition was not remarkably changed by chitosan; only arachidonic acid (20:4n-6) levels were significantly altered by CCl(4). Chitosan administration in the present experiment did not restore the decreased delta5-desaturase activity. In addition, chitosan supplementation did not prevent the CCl(4) induced degradation of CYP2E1. In conclusion, our results suggest that chitosan has antioxidative but not detoxifying effects on chronic CCl(4) induced hepatic injury in rats.     

Salidroside protects mice against CCl4-induced acute liver injury via down-regulating CYP2E1 expression and inhibiting NLRP3 inflammasome activation

Salidroside (Sal), a natural phenolic compound isolated from Rhodiola sachalinensis, has been utilized as anti-inflammatory and antioxidant for centuries, however, its effects against liver injury and the underlying mechanisms are unclear. This study was designed to evaluate the protective effects and underlying mechanisms of Sal on carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in mice. C57BL/6 mice were pretreated with Sal before CCl4 injection, the serum and liver tissue were collected to evaluate liver damage and molecular indices. The results showed that Sal pretreatment dose-dependently attenuated CCl4-induced acute liver injury, as indicated by lowering the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and inhibiting hepatic pathological damage and apoptosis. In addition, Sal alleviated CCl4-primed oxidative stress and inflammatory response by restoring hepatic glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and inhibiting cytokines. Finally, Sal also down-regulated the expression of cytochrome P4502E1 (CYP2E1), and Nod-like receptor protein 3 (NLRP3) inflammasome activation in the liver of mice by CCl4. Our study demonstrates that Sal exerts its hepatoprotective effects on ALI through its antioxidant and anti-inflammatory effects, which might be mediated by down-regulating CYP2E1 expression and inhibiting NLRP3 inflammasome activation.     

Meloxicam modulates oxidative stress status, inhibits prostaglandin E2, and abrogates apoptosis in carbon tetrachloride-induced rat hepatic injury

The current study aimed at investigating the potential hepatoprotective property and mechanism of meloxicam (MEL) against carbon tetrachloride (CCl(4))-induced hepatocellular damage in rats. Subcutaneous administration of CCl(4) (2 mL/kg, twice/week for 8 weeks) induced hepatocellular damage substantiated by hematoxylin and eosin staining and significant elevation in serum aspartate transaminase, alanine transaminase, and total bilirubin. In addition, CCL(4) treatment led to elevation in liver contents of lipid peroxidation marker (malondialdehyde), prostaglandin E2, active caspase 3, and Terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and reduction in the activities of superoxide dismutase, catalase, glutathione-S-transferase, and reduced glutathione in the liver tissue. Prior oral treatment with MEL (5 mg/kg, twice/week) retained the normal liver histology and significantly restored all of these parameters close to normal values. These results demonstrated the hepatoprotective utility of MEL against the CCl(4)-induced liver injury which might ascribe to its antioxidant, free radical scavenging, antiapoptotic and anti-inflammatory effects.     

Protective effect of caffeic acid phenethyl ester against carbon tetrachloride-induced hepatotoxicity in mice

This study was designed to investigate the protective effects of the phenethyl ester of caffeic acid (CAPE) against carbon tetrachoride (CCl₄)-induced hepatotoxicities in mice. Pretreatment with CAPE prior to administration of CCl₄ significantly prevented the increases in serum alanine, aspartate aminotransferase and alkaline phosphatase activities, hepatic lipid peroxidation formation, and depletion of glutathione content. In addition, CAPE prevented CCl₄-induced apoptosis and necrosis, as indicated by liver histopathology and DNA laddering studies. To determine whether the Fas/Fas ligand (FasL) pathway is involved in CCl₄-induced acute liver injury, Fas and FasL proteins and caspase-3 and -8 activities were tested by western blotting and ELISA. CAPE markedly decreased CCl₄-induced Fas/FasL protein expression levels and, in turn, attenuated CCl₄-induced caspase-3 and -8 activities in mouse liver. Moreover, the effect of CAPE on CYP2E1, the major isozyme involved in CCl₄ bioactivation, was investigated. Treatment with CAPE significantly decreased the CYP2E1-dependent hydroxylation of aniline. In addition, CAPE attenuated the CCl₄-mediated depletion of antioxidant enzyme (catalase, superoxide dismutase and glutathione-S-transferase) activities. These findings suggest that the protective effects of CAPE against CCl₄-induced acute liver injury may involve its ability to block CYP2El-mediated CCl₄ bioactivation and to protect against Fas/FasL-mediated apoptosis.     

Free radical scavenging and hepatoprotective actions of the medicinal herb, Crassocephalum crepidioides from the Okinawa Islands

Free radical scavenging and protective actions against chemically induced hepatotoxicity of Crassocephalum crepidioides were investigated. A water extract of C. crepidioides strongly scavenged superoxide anion, hydroxyl radical and also stable radical 1,1-diphenyl-2-picrylhydrazyl. Galactosamine (GalN, 400 mg/kg) and lipopolysaccharide (LPS, 0.5 microg/kg) induced hepatotoxicity of rats as seen by an elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and of lipid peroxidation in liver homogenates was significantly depressed when the herbal extract was given intraperitoneally 1 and 15 h before GalN and LPS treatment. Similarly, carbon tetrachloride (CCl4) induced liver injury as evidenced by an increase in AST and ALT activities in serum was also inhibited by the extract pretreatment. Isochlorogenic acids, quercetin and kaempferol glycosides were identified as active components of C. crepidioides with strong free radical scavenging action. These results demonstrate that C. crepidioides is a potent antioxidant and protective against GalN plus LPS- or CCl4-induced hepatotoxicity.     

Hepatoprotection of tea seed oil (Camellia oleifera Abel.) against CCl4-induced oxidative damage in rats.

The oil of tea seed (Camellia oleifera Abel.) is used extensively in China for cooking. This study was designed to evaluate the effects of tea seed oil on CCl(4)-induced acute hepatotoxicity in rats. Male SD rats (200+/-10 g) were pre-treated with tea seed oil (50, 100, and 150 g/kg diet) for six weeks before treatment with a single dose of CCl(4) (50% CCl(4), 2 mL/kg of bw, intraperitoneally), the rats were sacrificed 24h later, and blood samples were collected for assaying serum biochemical parameters. The livers were excised for evaluating peroxidation products and antioxidant substances, as well as the activities of antioxidant enzymes. Pathological histology was also performed. The results showed that a tea seed oil diet significantly (p<0.05) lowered the serum levels of hepatic enzyme markers (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase), inhibited fatty degeneration, reduced the content of the peroxidation product malondialdehyde, and elevated the content of GSH. Pre-treatment of animals with tea seed oil (150 g/kg diet) could increase the activities of glutathione peroxidase, glutathione reductase and glutathione S transferase in liver when compared with CCl(4)-treated group (p<0.05). Therefore, the results of this study show that a tea seed oil diet can be proposed to protect the liver against CCl(4)-induced oxidative damage in rats, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenger effects.     

Mechanism of antihepatotoxic activity of wuweizisu C and gomisin A1

The mechanism of inhibitory action of wuweizisu C and gomisin A in carbon tetrachloride (CCl (4))-induced liver damage was investigated by determining the effects of these substances on the steps of the series of events leading to liver lesion. Although wuweizisu C and gomisin A exerted no inhibition in CCl (3) radical formation, both lignans inhibited CCl (4)-, ADP/Fe (3+)- and ascorbate/Fe (2+)-induced lipid peroxidation, and wuweizisu C elicited stronger effects than gomisin A which is parallel with the results on antihepatotoxic effects in CCl (4)-induced cytotoxicity, indicating that anti-oxidative action plays an important part in the antihepatotoxic activity of wuweizisu C and gomisin A.     

Hepatoprotective potential of polyphenol rich extract of Murraya koenigii L.: an in vivo study

The present study investigates hepatoprotective effects of polyphenol rich Murraya koenigii L. (MK) hydro-ethanolic leaf extract in CCl(4) treated hepatotoxic rats. Plasma markers of hepatic damage, lipid peroxidation levels, enzymatic, and non-enzymatic antioxidants in liver and histopathological changes were investigated in control and treated rats. MK pretreated rats with different doses (200, 400 and 600mg/kg body weight) showed significant decrement in activity levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and bilirubin. Also, MK treated rats recorded a dose dependent increment in hepatic super oxide dismutase, catalase, reduced glutathione and ascorbic acid and, a decrement in lipid peroxidation. Microscopic evaluations of liver revealed CCl(4)-induced lesions and related toxic manifestations that were minimal in liver of rats pretreated with MK extract. These results demonstrate that hydro-ethanolic leaf extract of MK possesses hepatoprotective potentials.