N-acetylcysteine attenuates dimethylnitrosamine induced oxidative stress in rats

Oxidative stress has been implicated in the pathogenesis and progression of various hepatic disorders and hence screening for a good hepatoprotective and antioxidant agent is the need of the hour. The present study was aimed to investigate the hepatoprotective and antioxidant property of N-acetylcysteine (NAC) against dimethylnitrosamine (DMN) induced oxidative stress and hepatocellular damage in male Wistar albino rats. Administration of single dose of DMN (5 mg/kg b.w.; i.p.) resulted in significant elevation in the levels of serum aspartate transaminase and alanine transaminase, indicating hepatocellular damage. Oxidative stress induced by DMN treatment was confirmed by an elevation in the status of lipid peroxidation (LPO) and reduction in the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and in the levels of non-enzymic antioxidants, reduced glutathione, vitamin-C and vitamin-E in the liver tissue. DMN induced oxidative stress and hepatocellular membrane instability was further substantiated by a decline in the status of the membrane bound ATPases in the liver tissue. Post-treatment with NAC (50 mg/kg b.w.; p.o.) for 7 days effectively protected against the DMN induced insult to liver by preventing the elevation in the status of the serum marker enzymes and LPO, and restoring the activities of both the enzymic and non-enzymic antioxidants and membrane bound ATPases towards normalcy. These results demonstrate that NAC acts as a good hepatoprotective and antioxidant agent in attenuating DMN induced oxidative stress and hepatocellular damage.     

Hepatoprotective and antioxidant effects of gallic acid in paracetamol‐induced liver damage in mice

Objectives The aim of this research paper was to investigate the hepatoprotective and antioxidant effects of gallic acid in paracetamol‐induced liver damage in mice. Methods In the present study, the hepatoprotective and antioxidant effects of gallic acid were evaluated against paracetamol‐induced hepatotoxicity in mice and compared with the silymarin, a standard hepatoprotective drug. The mice received a single dose of paracetamol (900 mg/kg body weight i.p.). Gallic acid (100 mg/kg body weight i.p.) and silymarin (25 mg/kg body weight i.p.) were administered 30 min after the injection of paracetamol. After 4 h, liver marker enzymes (aspartate transaminase, alanine transaminase and alkaline phosphatase) and inflammatory mediator tumour necrosis factor‐alpha (TNF‐α) were estimated in serum, while the lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase and glutathione) were determined in liver homogenate of the control and experimental mice. Key findings Increased activities of liver marker enzymes and elevated TNF‐α and lipid peroxidation levels were observed in mice exposed to paracetamol (P < 0.05), whereas the antioxidant status was found to be depleted (P < 0.05) when compared with the control group. However gallic acid treatment (100 mg/kg body weight i.p.) significantly reverses (P < 0.05) the above changes by its antioxidant action compared to the control group as observed in the paracetamol‐challenged mice. Conclusions The results clearly demonstrate that gallic acid possesses promising hepatoprotective effects.     

Hepatoprotective activity of methanolic extract of Hiptage bengalensis leaves against CCl₄-induced hepatotoxicity in rats

The objective of the present study was to evaluate hepatoprotective activity of methanolic extract of Hiptage bengalensis (L.) kurz (MEHB) in rats. Hepatic damage was induced by administration of carbontetrachloride(1 ml/kg, b.w, p.o.) in combination with liquid paraffin (1:1) as a single dose on 7th day. The extent of liver damage was studied by estimating biochemical parameters. Administration of MEHB (200 mg & 400 mg/kg) for 6 days before carbontetrachloride administration showed a significant reduction (p < 0.01) of serum liver damage enzymes markers-aspartate transaminase, alanine transaminase, total bilirubin and alkaline phosphatase (ALP). Histopathological changes of hepatic tissue were also evaluated in control and MEHB treated groups. Results also indicated that MEHB possessed potential antioxidant effect by increasing the levels of glutathione and also possessed free radical scavenging activities. The hepatoprotective effect of Hiptage bengalensis (L.) kurz was comparable to standard drug silymarin (50 mg/kg).     

Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats

Oxidative stress plays a pivotal role in the pathogenesis and progression of gamma-irradiation induced cellular damage and the administration of dietary antioxidants has been suggested to protect against the subsequent tissue damage. Here, we present the data to explore the hepatoprotective and antioxidant effect of hesperidin, a naturally occurring citrus flavanoglycone, against gamma-irradiation induced oxidative damage in the liver of rats. Healthy male Sprague-Dawley rats were exposed to gamma-irradiation (1 Gy, 3 Gy and 5 Gy) and were administered hesperidin (50 mg/kg and 100 mg/kg, b.w, orally) for 7 days post irradiation. The changes in body weight, liver weight, spleen index, serum and liver aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and serum ceruloplasmin levels were determined along with differences in the liver histopathology. Liver thiobarbuturic acid reactive substance as an index for lipid peroxidation and the levels of enzymatic antioxidants like superoxide dismutase, catalase, glutathione peroxidase and the status of non-enzymatic antioxidants as an index for oxidative stress were also determined. Exposure to gamma-irradiation resulted in hepatocellular damage in a dose-dependent manner, featuring a significantly decreased body weight and liver weight and higher levels of serum AST, ALT, ALP, LDH and gamma-GT levels and a simultaneous decrease in their levels in the liver tissue. Oxidative stress was evidenced by elevated levels of lipid peroxidation and a decrease in the levels of key enzymatic and non-enzymatic antioxidants in the liver. However, the gamma-irradiation induced toxic effects were dramatically and dose-dependently inhibited by hesperidin treatment as observed by the restoration in the altered levels of the marker enzymes, lipid peroxidation, enzymatic and non-enzymatic antioxidants. The results of the biochemical observations were supported by the histopathological findings. Thus, oral administration of hesperidin was found to offer protection against gamma-irradiation induced hepatocellular damage and oxidative stress in rats, probably by exerting a protective effect against hepatocellular necrosis via its free radical scavenging and membrane stabilizing ability.     

Hepatoprotective activity of methanolic extract of Hiptage bengalensis leaves against CCl4-induced hepatotoxicity in rats

The objective of the present study was to evaluate hepatoprotective activity of methanolic extract of Hiptage bengalensis (L.) kurz (MEHB) in rats. Hepatic damage was induced by administration of carbontetrachloride(1 ml/kg, b.w, p.o.) in combination with liquid paraffin (1:1) as a single dose on 7th day. The extent of liver damage was studied by estimating biochemical parameters. Administration of MEHB (200 mg & 400 mg/kg) for 6 days before carbontetrachloride administration showed a significant reduction (p < 0.01) of serum liver damage enzymes markers-aspartate transaminase, alanine transaminase, total bilirubin and alkaline phosphatase (ALP). Histopathological changes of hepatic tissue were also evaluated in control and MEHB treated groups. Results also indicated that MEHB possessed potential antioxidant effect by increasing the levels of glutathione and also possessed free radical scavenging activities. The hepatoprotective effect of Hiptage bengalensis (L.) kurz was comparable to standard drug silymarin (50 mg/kg).     

Hepatoprotective activity of Amaranthus spinosus in experimental animals

The hepatoprotective and antioxidant activity of 50% ethanolic extract of whole plant of Amaranthus spinosus (ASE) was evaluated against carbon tetrachloride (CCl₄) induced hepatic damage in rats. The ASE at dose of 100, 200 and 400 mg/kg were administered orally once daily for fourteen days. The substantially elevated serum enzymatic levels of serum glutamate oxaloacetate transaminase (AST), serum glutamate pyruvate transaminase (ALT), serum alkaline phosphatase (SALP) and total bilirubin were restored towards normalization significantly by the ASE in a dose dependent manner. Higher dose exhibited significant hepatoprotective activity against carbon tetrachloride induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. Meanwhile, in vivo antioxidant activities as malondialdehyde (MDA), hydroperoxides, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were also screened which were also found significantly positive in a dose dependent manner. The results of this study strongly indicate that whole plants of A. spinosus have potent hepatoprotective activity against carbon tetrachloride induced hepatic damage in experimental animals. This study suggests that possible mechanism of this activity may be due to the presence of flavonoids and phenolics compound in the ASE which may be responsible to hepatoprotective activity.     

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.     

Silymarin: An Effective Hepatoprotective Agent Against Diethylnitrosamine-Induced Hepatotoxicity in Rats

Abstract

This study investigates the putative hepatoprotective and antioxidant activity of silymarin (SIL) on diethylnitrosamine (DEN)-induced liver damage in male Wistar rats. A single intraperitoneal administration of DEN (200 mg/kg) to rats resulted in significantly elevated serum levels of AST, ALT, ALP, LDH, γ-GT, and BIL compared with controls after 30 days in serum. In contrast, the liver tissue showed a significant decrease in the levels of AST, ALT, and ALP, and an increase in LDH and γ-GT. Elevated levels of lipid peroxidation (LPO) were observed in the liver tissue after DEN administration. Quantitative analysis of catalase (CAT) and superoxide dismutase (SOD) revealed lower activities of these key antioxidant enzymes in the liver upon DEN administration. The status of antioxidant vitamins, vitamin C and vitamin E, were also found to be decreased in DEN-exposed rats. When rats with DEN-induced hepatotoxicity were treated with SIL (50 mg/kg, orally) for 30 days, the levels of AST, ALT, ALP, LDH, γ-GT, and BIL reverted to near normalcy, whereas the hepatic concentration of CAT, SOD, vitamin C, and vitamin E were significantly increased, and that of LPO significantly lowered, when compared with DEN-exposed, untreated rats. These results suggest that SIL is able to significantly alleviate the hepatotoxicity and oxidative stress induced by DEN in rats.     

Protection against thallium hepatotoxicity by silymarin

The effect of silymarin (100 mg/kg i.p.) on the biochemical indicators of liver damage induced by thallium (10 mg/kg p.o.) was studied in rats. The production of malondialdehyde and the content of reduced glutathione in the liver were measured as indicators of lipid peroxidation. Thallium intoxication increased the serum activities of glutamic pyruvic transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase and the liver concentration of triglycerides. Thallium decreased the activity of alkaline phosphatase and increased that of gamma-glutamyl transpeptidase in the liver cell membrane. It also abolished the membrane activity of Na+/K+ ATPase. Lipid peroxidation was enhanced by thallium as malondialdehyde production was increased and the content of reduced glutathione was decreased in the liver. Silymarin completely prevented all these changes. It is suggested that thallium toxicity is due, at least in part, to the promotion of lipid peroxidation. The membrane stabilizing effect of silymarin observed in this and in other models of liver toxicity is due to some antioxidant property, possibly related to its ability to scavenge free oxygen radicals.     

Nelumbo nucifera leaf extract treatment attenuated preneoplastic lesions and oxidative stress in the livers of diethylnitrosamine‐treated rats

Lotus (Nelumbo nucifera Gaertn) possesses antioxidant, hepatoprotective, and anticancer potential. This study determined the protective role of aqueous extract from Nelumbo nucifera leaves (NLE) against N‐diethylnitrosamine (DEN)‐induced oxidative stress and hepatocellular carcinogenesis in a sample of Sprague–Dawley rats. NLE was fed orally to rats in which hepatic carcinoma was induced with DEN for 12 weeks. Five groups of 12 rats each were used for the study: Group I (control group) rats received distilled water; Group II rats were induced with DEN; Group III rats were induced with DEN and cotreated with 0.5% NLE; Group IV rats were induced with DEN and cotreated with 1.0% NLE; and Group V rats were induced with DEN and cotreated with 2.0% NLE. Clinical chemistry, organ weight, inflammatory marker, protein expression, enzyme, and antioxidant analyses were conducted. NLE administration to rats resulted in significantly decreased levels of serum alanine aminotransferase, aspartate aminotransferase, and albumin, which is indicative of hepatocellular damage, compared with the control group. DEN‐induced oxidative stress was inhibited by NLE and this inhibition was paralleled by decreased lipid peroxides and increased glutathione transferase, superoxide dismutase, catalase, and glutathione peroxidase activity in liver tissues. The status of nonenzymatic antioxidants, such as reduced glutathione, was also found to be increased in NLE‐administered rats. Furthermore, NLE decreased tumor size, hepatic Rac1, PKCα, and GSTπ expressions compared with the DEN‐only group. Thus, supplementation of NLE reduced the adverse changes that occur because of liver cancer. These results prove that NLE protects against liver carcinogenesis induced because of treatment with DEN through blocking lipid peroxidation, hepatic cell damage, and enhancing the antioxidant defense system.     

Effects of phenolic compounds on bromobenzenemediated hepatotoxicity in mice

1. The hepatic protective effects of the phenolic compounds 7,8-dihydroxyflavone, morin, silymarin, caffeic acid and chlorogenic acid on bromobenzene-induced toxicity in mice were studied.

2. Morin, caffeic acid and chlorogenic acid at an oral dose of 200mg/kg failed to influence hepatotoxicity in vivo, while 7,8-dihydroxyflavone exhibited efficacy and potency higher than those of the reference compound silymarin.

3. 7,8-Dihydroxyflavone, an antioxidant and hepatoprotective agent in vitro, decreased serum glutamate-pyruvate transaminase levels (SGPT) in a dose-related manner, and at 200mg/kg inhibited bromobenzene-induced glutathione depletion in liver.     

Evaluation of hepatoprotective efficacy of Majoon‐e‐Dabeed‐ul‐ward against acetaminophen‐induced liver damage: A Unani herbal formulation

A Unani herbal formulation known as Majoon‐e‐Dabeed‐ul‐ward (MD) was evaluated for hepatoprotective effect against acetaminophen (APAP; 2 g/kg p.o.)‐induced liver damage. The latter was evidenced by elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), serum alkaline transaminase (SALP), lactate dehydrogenase (LDH), bilirubin, albumin, urea, and creatinine in experimental animals. Increased levels of lipid peroxidation were associated with a concomitant decline in reduced glutathione levels, adenosine triphosphatase (ATPase), and glucose‐6‐phosphatase (G‐6‐Pase) caused by APAP treatment. Treatment with MD (250,500, and 1,000 mg/kg p.o.) reverse the altered levels of AST, ALT, SALP, LDH, bilirubin, albumin, urea, and creatinine in a dose‐dependent manner. Significant restoration was found in LPO, GSH content and metabolic enzymes (ATPase and G‐6‐pase) were seen after therapy. The herbal formulation, MD showed hepatoprotective efficacy against APAP‐induced liver damage. Drug Dev Res 72: 346–352, 2011. © 2010 Wiley‐Liss, Inc.     

Hepatoprotective Effect of Cissus quadrangularis Stem Extract Against Rifampicin-induced Hepatotoxicity in Rats

The study was designed to investigate the hepatoprotective activity of methanol extract of Cissus quadrangularis against rifampicin-induced hepatotoxicity in rats.The coarse powder of the shade dried stem of Cissus quadrangularis was subjected to successive extraction in a Soxhlet apparatus using solvents petroleum ether (60-80°) and methanol. Liver damage was induced in Wistar rats by administering rifampicin (54 mg/kg, p.o.) once daily for 30 days. Methanol extract of Cissus quadrangularis (500 mg/kg, p.o) was administered 1 h prior to the administration of rifampicin (54 mg/kg, p.o.) once daily for 30 days. Silymarin (50 mg/kg p.o) used as reference drug. Elevated levels of aspartate transaminase, alanine transaminase, alkaline posphatase and bilirubin following rifampicin induction were significantly lowered due to pretreatment with methanol extract of Cissus quadrangularis. Rifampicin administration significantly increased lipid peroxidation and decreased antioxidant activities like reduced glutathione, superoxide dismutas and catalase. Pretreatment of rats with methanol extract of Cissus quadrangularis significantly decreased lipid peroxidation and increased the antioxidant activities. Histology of the liver section of the animals treated with the methanol extract of Cissus quadrangularis further confirms the hepatoprotective activity. The results of the present study indicated the hepatoprotective effect of methanol extract of Cissus quadrangularis which might be ascribable to its antioxidant property due to the presence of β-carotene.     

Protective Effect of Ethanol Extract of Gymnosporia montana (Roth) Bemth. in Paracetamol-induced Hepatotoxicity in Rats

The aim of the present study was to explore the hepatoprotective activity of the ethanol extract of leaves of Gymnosporia montana (Roth) Bemth. (Family: Celastraceous) against paracetamol-induced hepatotoxicity. Hepatotoxicity in Wistar rats was induced by a single intraperitoneal dose of 500 mg/kg of paracetamol and studied by comparing parameters such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase and histopathological examination of liver. Pre and post-treatment with ethanol extract of Gymnosporia montana (Roth) Bemth. at doses of 50 and 100 mg/kg was studied by comparing the above mentioned parameters with silymarin (100 mg/kg) as standard. Both doses of ethanol extract of Gymnosporia montana (Roth) Bemth. were found to be hepatoprotective. Extract at the dose of 100 mg/kg produced effects comparable to those of silymarin. The present study indicates that alcohol extract of Gymnosporia montana (Roth) Bemth. possessed significant hepatoprotective activity.     

Antioxidant activity of the oyster mushroom, Pleurotus ostreatus, on CCl4-induced liver injury in rats

This study was undertaken to investigate the putative antioxidant activity of the oyster mushroom Pleurotus ostreatus on CCl₄-induced liver damage in male Wistar rats. Intraperitoneal administration of CCl₄ (2 ml/kg) to rats for 4 days resulted in significantly elevated (p < 0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT) and alkaline phosphatase (SALP) compared to controls. In the liver, significantly elevated levels (p < 0.05) of malondialdehyde (MDA) and lowered levels (p < 0.05) of reduced glutathione (GSH) were observed following CCl₄ administration. Quantitative and qualitative analysis of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) revealed lower activities of these antioxidant enzymes in the liver of CCl₄-administered rats. An analysis of the isozyme pattern of these enzymes revealed variations in relative concentration presumably due to hepatotoxicity. When rats with CCl₄-induced hepatotoxicity were treated with the extract of P. ostreatus, the serum SGOT, SGPT and SALP levels reverted to near normal, while the hepatic concentration of GSH, CAT, SOD and Gpx were significantly increased (p < 0.05) and that of MDA significantly (p < 0.05) lowered, when compared to CCl₄-exposed untreated rats. Histopathological studies confirmed the hepatoprotective effect conferred by the extract of P. ostreatus. These results suggest that an extract of P. ostreatus is able to significantly alleviate the hepatotoxicity induced by CCl₄ in the rat.     

Silymarin protection against major reactive oxygen species released by environmental toxins: exogenous H2O2 exposure in erythrocytes

Silymarin is a polyphenolic plant flavonoid (a mixture of flavonoid isomers such as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin marianum that has anti-inflammatory, hepatoprotective and anticarcinogenic effects. Our earlier studies have shown that silymarin plays a protective role against the oxidative damage induced by environmental contaminants like benzo(a)pyrene in erythrocyte haemolysates. During the detoxification of these environmental contaminants, the major reactive oxygen species generated is hydrogen peroxide (H(2)O(2)). Because H(2)O(2 )can easily penetrate into the cell and cause damage to biomolecules, the protective role of silymarin was further assessed against this cytotoxic agent in vitro in erythrocyte haemolysates. The protective effect was monitored by assessing the levels of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-s-transferase, glutathione peroxidase and malondialdehyde (LPO) in three groups: vehicle control, H(2)O(2)-exposed groups and drug co-incubation group (H(2)O(2) + silymarin). The protective effect of silymarin on the non-enzymic antioxidant glutathione and haemolysis, methaemoglobin content and protein carbonyl content were also assessed. It was observed that the activities of antioxidant enzymes and glutathione were reduced and the malondialdehyde levels were elevated after H(2)O(2 )exposure. There were also alterations in haemolysis, methaemoglobin content and protein carbonyl content, whereas after the administration of silymarin, the antioxidant enzyme activities reversed to near normal with reduced malondialdehyde content and normalized haemolysis, methaemoglobin content and protein carbonyl content. The results suggest that silymarin possesses substantial protective effect and free radical scavenging mechanism against exogenous H(2)O(2)-induced oxidative stress damages, hence, can be used as a protective drug against toxicity induced by environmental contaminants.     

Hepatoprotective and antioxidant effects of baicalin against CCl4-induced hepatotoxicity

Scutellaria baicalensis is widely cultivated in eastern Asia, particularly in China. In the present study, we isolated baicalin from this plant and studied for its hepatoprotective activity against CCl₄-induced oxidative damage in rats. Our findings revealed that baicalin exhibited strong antioxidant activity in vitro. In established in vivo tests, baicalin showed effective protective effects by reducing the elevated levels of glutamate pyruvate transaminase(ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), total bilirubin (TB) and malondialdehyde (MDA) against CCl₄-induced damage, and it restored the activities antioxidant defense substances, such as superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH), toward their normal levels. These data were supplemented with histopathological examination of rat liver sections. The results demonstrated that baicalin could be proposed to protect the liver against CCl₄-induced oxidative damage in rats, and the possible underlying mechanism of the activity could be due to its free radical-scavenging and antioxidant activity.     

The protective mechanism of Nigella sativa against diethylnitrosamine‐induced hepatocellular carcinoma through its antioxidant effect and EGFR/ERK1/2 signaling

A wide variety of natural products have powerful chemopreventive effects due to their antioxidant, antimutagenic, and anti‐inflammatory activities that enable them to arrest cell proliferation in several cancer models. In the present study, we shed light on the protective mechanism of Nigella sativa extract against diethylnitrosamine (DENA)‐induced preneoplastic stage of hepatocellular carcinoma (HCC) in rats. We studied the extract effect on EGFR/ERK1/2 signaling pathway as one of the major signaling pathways controlling cell proliferation during hepatocarcinogenesis as well as the investigation of its antioxidant activity. The study also compared the effects of NSEE to those of (thymoquinone) TQ and silymarin as hepatoprotective substances. Rats received daily doses of NSEE (150, 250, 350 mg/kg BW), a dose per three alternative days/week of TQ (20 mg/kg BW) and a daily dose of silymarin (100 mg/kg BW). The doses were administered orally by gavage for 12 days before DENA and CCl₄ administration, and then the supply of NSEE, TQ or silymarin was continued until the end of the experiment (16 weeks). DENA administration activated EGFR/ERK1/2 signaling and caused a significant increase in P‐EGFR and P‐ERK1/2 as well as a significant up‐regulation of expression of target genes such as PCNA, c‐fos and Bcl2, which indicated the increase in cell proliferation. Furthermore, a significant elevation in alpha‐fetoprotein (AFP) and hepatic enzymes was observed in DENA‐treated rats in addition to a decrease in the antioxidant status. The protection with NSEE, TQ, or silymarin has the potential to inhibit the EGFR/ERK1/2 activation and improve the antioxidant status. Moreover, the action of NSEE against the hepatocarcinogenesis was supported by high antioxidant activity and the histopathological observations of the liver. These data suggest that NSEE has a chemopreventive role in DENA‐induced HCC through the inhibition of the EGFR/ERK1/2 signaling pathway and their target genes in addition to its role as an antioxidant.     

Effects of bergenin, the major constituent of Mallotus japonicus against D-galactosamine-induced hepatotoxicity in rats

The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against D-galactosamine (GalN)-induced liver damage in rats. Bergenin (50, 100 and 200 mg/kg) was given orally once daily for 7 successive days and then GalN 400 mg/kg was injected intraperitoneally to rats at 24 and 96 h after the final administration of bergenin. Pretreatment with bergenin reduced the increased enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase, gamma-glutamyltransferase and the elevated level of malondialdehyde induced by GalN. Bergenin restored the decreased hepatic contents of glutathione as well as the decreased activities of glutathione S-transferase and glutathione reductase by GalN towards normalization, suggesting that the hepatoprotective effects of bergenin may consist in maintaining adequate levels of hepatic glutathione for the removal of xenobiotics. The present results indicate that bergenin has hepatoprotective effects against GalN-induced hepatotoxicity in rats.     

Protective potential of Royal Jelly against carbon tetrachloride induced-toxicity and changes in the serum sialic acid levels

Royal Jelly (RJ) is used in the Turkish folk medicine for the treatment of number of disorders. The present study describes the hepatoprotective and antioxidant activities of the RJ against carbon tetrachloride (CCl₄)-induced acute liver damage. Sprague–Dawley rats were used for the experiment. CCl₄ (0.8 ml/kg; s.c.) and RJ (50, 100, 200 mg/kg; orally) were given every other day, for 20 days. Malondialdehyde, reduced glutathione in whole blood and tissues; ceruloplasmin, sialic acid, ascorbic acid, retinol, β-carotene and liver enzymes levels in serum were measured. Additionally, histopathological alterations in the liver were examined. RJ exerted the significant protective effect on liver damage as well as on oxidative stress induced by CCl₄, resulting in reduced lipid peroxidation and improved endogenous antioxidant defence systems. It also reduced the elevated levels of liver enzymes. Histopathological study further confirmed the hepatoprotective effect of RJ, when compared with the CCl₄ treated control groups. In conclusion, present study reveals biological evidence that supports the use of RJ in the treatment of chemical-induced hepatotoxicity.