Antioxidant and hepatoprotective effects of ethanol extract of Vitex glabrata on carbon tetrachloride-induced liver damage in rats

This study was aimed at evaluating the antioxidant and hepatoprotective effects of the ethanol extract of Vitex glabrata (EEVG) in a CCl(4)-induced liver damage model in rats; and to isolate and characterise the bioactive constituent from EEVG. Hepatoprotective activity was evaluated by changes in the levels of the serum enzymes viz. AST, ALT, ALP and total bilirubin, and further by histopathological examinations of liver tissues. Antioxidant activity was measured in terms of superoxide dismutase, GSH, lipid peroxidation (LPO), catalase and peroxidase levels in liver homogenate. The pentamethoxy flavonoid artemetin was isolated and characterised from EEVG. Artemetin and EEVG pre-treatment significantly (p?相似文献   

Effect of paeonol on antioxidant and immune regulatory activity in hepatocellular carcinoma rats

The study investigated the immunity and antioxidant potential of paeonol by employing a hepatocellular carcinoma (HCC) rat model. Three doses of paeonol (20, 40, 60 mg/kg b.w. orally) were administrated to diethylnitrosamine (DEN)-induced HCC rats. Results showed that paeonol significantly reduced the serum AST, ALT, ALP, GGT, AFU and liver MDA levels, increased serum WBC, TP, ALB, A/G, TNF-α and IFN-γ and liver antioxidant enzymes activities (SOD, CAT, GSH-Px, GR) in HCC rats. Altogether, these results suggest that the paeonol could effectively decrease oxidative injury and improve immunity function in HCC rats.     

抑肽酶对D-氨基半乳糖大鼠急性肝损伤的保护作用

探讨抑肽酶对D-氨基半乳糖致Wistar大鼠急性肝损伤的保护作用.利用D-氨基半乳糖(D-GalN)诱导Wistar大鼠急性肝损伤模型进行研究,检测各组大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、白蛋白(ALB)、白蛋白总蛋白比值(A/G),观察光镜下肝组织的病理改变.结果显示,经腹腔注射抑肽酶对D-氨基半乳糖所造成的急性肝损伤有明显的保护作用.     

Snailase preparation of ginsenoside M1 from protopanaxadiol-type ginsenoside and their protective effects against CCl4-induced chronic hepatotoxicity in mice

To investigate the protective effects of protopanaxadiol-type ginsenoside (PDG) and its metabolite ginsenoside M1 (G-M1) on carbon tetrachloride (CCl(4))-induced chronic liver injury in ICR mice, we carried out conversion of protopanaxadiol-type ginsenosides to ginsenoside M1 using snailase. The optimum time for the conversion was 24 h at a constant pH of 4.5 and an optimum temperature of 50 °C. The transformation products were identified by high-performance liquid chromatography and electrospray ion-mass spectrometry. Subsequently, most of PDG was decomposed and converted into G-M1 by 24 h post-reaction. During the study on hepatoprotective in a mice model of chronic liver injury, PDG or G-M1 supplement significantly ameliorated the CCl(4)-induced liver lesions, lowered the serum levels of select hepatic enzyme markers (alanine aminotransferase, ALT, and aspartate aminotransferase, AST) and malondialdehyde and increased the activity of superoxide dismutase in liver. Histopathology of the liver tissues showed that PDG and G-M1 attenuated the hepatocellular necrosis and led to reduction of inflammatory cell infiltration. Therefore, the results of this study show that PDG and G-M1 can be proposed to protect the liver against CCl(4)-induced oxidative injury in mice, and the hepatoprotective effect might be attributed to amelioration of oxidative stress.     

Potential of <Emphasis Type="Italic">Crocus sativus</Emphasis> (saffron) and its Constituent,Crocin, as Hypolipidemic and Antioxidant in Rats

The aim of the present study was to evaluate the hypolipidemic and antioxidant potential of saffron and its active constituent, crocin, in hyperlipidemic rats. The animals fed either with normal fat diet or high fat diet were administered orally saffron (25, 50, and 100 mg/kg) or crocin (4.84, 9.69, and 19.38 mg/kg) in their respective groups for five consecutive days. Biochemical estimations of triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alkaline phosphatase (ALP), aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), glutathione peroxidase enzyme activity (GSHPx), total glutathione (GSH), and oxidized glutathione (GSSG) in serum and superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive species (TBARS), ferric reducing/antioxidant power (FRAP), and total sulfhydryl (SH) groups in liver tissue homogenate were carried out. Both saffron and crocin were effective in decreasing the elevated levels of TG, TC, ALP, AST, ALT, MDA, GSHPx, GSH, and GSSG in serum and increasing SOD, CAT, FRAP, and SH values in liver tissue with reduction in TBARS. The saffron was found to be superior to crocin indicating the involvement of other potential constituents of saffron apart from crocin for its synergistic behavior of quenching the free radicals and ameliorating the damages of hyperlipidemia.     

Increase in the plasma protein binding of weakly basic drugs in carbon tetrachloride-intoxicated rats.

Plasma protein binding of weakly basic drugs such as propranolol and quinidine was determined in rats with carbon tetrachloride (CCl4)-induced hepatic disease. Free fractions of propranolol and quinidine in the plasma of rats at 24 h after CCl4-intoxication were decreased by 41 and 30%, respectively, compared to those of control rats. An addition of Tris (butoxyethyl) phosphate (TBEP), a specific displacer for basic drugs from alpha 1-acid glycoprotein (AGP), to the plasma increased the free fractions of the basic drugs, resulting in no difference in the extent of the plasma free fraction of each drug between control and CCl4-intoxicated rats. Plasma concentration of AGP in CCl4-intoxicated rats was elevated 2.7-fold of that in control rats at 24 h after the CCl4 intoxication and reached a peak of 4.8-fold elevation at 48 h. A regression analysis revealed a high degree of positive correlation between ratios of bound to free fraction of propranolol and plasma concentrations of AGP. These results suggest that the plasma protein binding of the basic drugs was increased mainly due to the rise in the plasma AGP concentration in CCl4-intoxicated rats.     

Structural modifications of serum transthyretin in rats during protein-energy malnutrition

Transthyretin (TTR) is a sensitive marker of protein-energy malnutrition and changes in serum and expression levels during protein and energy deficiency are well described. However, little is known about structural modifications of TTR during protein and/or energy deprivation. Therefore, the aim of this study was to determine the effects of protein inadequacies on post-translational modifications of TTR. For this purpose, male Wistar rats were fed a diet with either casein or gelatine as sole protein source subsequent to a protein wash-out period. Changes in TTR serum levels as well as other markers of nutritional status as body weight, food consumption, total serum protein and serum RBP4 levels as well as antioxidative capacity were determined. Post-translational modifications of TTR were examined by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS) analysis. The rats from the gelatine group revealed a marked change in the post-translational modification pattern of TTR which was reflected by a significant elevation of sulfonated TTR and which was inversely correlated to the antioxidative capacity. Additionally, the elevation of sulfonated TTR was accompanied by a decrease in body weight and food consumption, low antioxidative capacity as well as a deprivation of serum TTR, RBP4 and total serum protein levels in the animals of the gelatine group. Protein-energy malnutrition leads therefore next to changes in TTR serum concentration, also to changes in the post-translational modification pattern of TTR. Such changes are probably induced by protein-energy malnutrition-driven oxidative stress and might be linked to alterations in protein function and stability.     

Multienzyme-modified biosensing surface for the electrochemical analysis of aspartate transaminase and alanine transaminase in human plasma

We investigated the electrochemical detection of aspartate transaminase (AST) and alanine transaminase (ALT) by using a multienzyme-modified electrode surface. Determination of the activities of transaminases in human serum is clinically significant because their concentrations and ratios indicate the presence of hepatic diseases or myocardial dysfunction. For electrochemical detection of AST and ALT, enzymes that participate in the reaction mechanism of AST and ALT, such as pyruvate oxidase (POX) and oxaloacetate decarboxylase, were immobilized on an electrode surface by using an amine-reactive self-assembled monolayer and a homobifunctional cross-linker. In the presence of suitable substrates such as l-aspartate (l-alanine) and α-ketoglutarate, AST and ALT generate pyruvate as an enzymatic end product. To determine the activities of AST and ALT, electroanalyses of pyruvate were conducted using a POX and ferrocenemethanol electron shuttle. Anodically generated oxidative currents from multienzyme-mediated reactions were correlated to AST and ALT levels in human plasma. On the basis of the electrochemical analysis, we obtained calibration results for AST and ALT concentrations from 7.5 to 720 units/L in human plasma-based samples, covering the required clinical detection range.     

Acute toxicity and hepatotoxicokinetic studies of Tamarindus indica extract

Tamarindus indica is widely used as a food and beverage and in traditional medicine. The apparent lack of dose standardization in herbal medicine necessitates the evaluation of the lethality T. indica on Artemia salina nauplii and chicken embryos via in vitro and in vivo techniques. Furthermore, hepatotoxicokinetics of the crude extract and fractions on Wister rats was also assessed. At concentrations of 200, 20 and 2 μg/mL, crude extract and fractions showed brine shrimp death percentages ranging from 86.70% to 3.30% and the sub-fractions showed death percentage ranges of 46.70% to 3.30%. Calculated LD?? values ranged from 832 μg/mL to 5,019 μg/mL. Dosing Wister rats with 25% and 50% concentration of LD?? determined for crude extract and fractions on chicken embryos showed an elevation in the ALT and AST levels in the serum. Brine shrimps and chicken embryos showed a positive correlation, with R2 values of 0.541 and 0.588 (P ≤ 0.05) for fractions and subfractions, respectively, as media for the lethality assay. Dose standardization in folk herbal medicine is imperative as T. indica used as food and medicine has been shown to be toxic at high doses. Brine shrimp and chicken embryos may be comparably used as medium for toxicity assay.     

Effects of Lycium barbarum aqueous and ethanol extracts on high-fat-diet induced oxidative stress in rat liver tissue

This study evaluated the protective effects of aqueous extract of Lycium barbarum (LBAE) and ethanol extract of Lycium barbarum (LBEE) on blood lipid levels, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities and liver tissue antioxidant enzyme activities in rats fed a high fat diet (HF). The rats were randomly divided into seven groups of ten rats each and fed a different diet for eight weeks as follows: One group (NC group) was fed a standard diet, one group was fed a high-fat diet (HF group), one group was fed a high-fat diet and orally fed with 20 mg/kg b.w. simvastatin (HF + simvastatin group), and the other group was fed the high fat diet and orally fed with 50 mg/kg b.w. or 100 mg/kg b.w. LBAE (HF + LBAE), or 50 mg/kg b.w. or 100 mg/kg b.w. LBEE (HF + LBEE), respectively. After eight weeks, the HF diet caused deleterious metabolic effects. Rats fed the HF diet alone showed increased hepatocellular enzyme activities in plasma, a significant decline in antioxidant enzyme activities, and elevated liver lipid peroxidation indices. LBAE and LBEE administration significantly reduced liver damage and oxidative changes, and brought back the antioxidants and lipids towards normal levels. These data suggest that these antioxidants protect against toxicity parameters in HF rats.     

The effect of Lycium barbarum polysaccharide on alcohol-induced oxidative stress in rats

The aim of this study was to investigate the effects of Lycium barbarum polysaccharide (LBP) on alcohol-induced liver damage in rats. A total of 36 rats were divided into control, ethanol and ethanol + LBP groups. Rats in the ethanol group were fed 7 g ethanol/kg body weight by gastric infusion, three times a day, for 30 consecutive days, while rats in the control group received the same volume of physiological saline instead of ethanol, and rats in ethanol + LBP group were fed both ethanol (7 g/kg body weight) and LBP (300 mg/kg body weight/day). Alcoholic liver injury was examined by serum ALT and AST activities, alcoholic fatty liver was assessed by lipid levels, and oxidative stress was evaluated by SOD, CAT, GSH-Px, GSH and MDA assays. In the ethanol group, a significant elevation of enzymes and lipid in serum, increased MDA level and depletion of SOD, CAT, GSH-Px and GSH in liver were observed. LBP administration significantly ameliorated liver injury, prevented the progression of alcohol-induced fatty liver, and improved the antioxidant functions when compared with the ethanol group. Histopathological examination of rat liver revealed that LBP administration protected liver cells from the damage induced by ethanol. The results suggest that LBP is a promising agent to protect the liver from hepatotoxicity and fatty liver induced by ethanol intake.     

Protective effects of various Chinese traditional medicines against experimental cholestasis

In a previous paper, we reported that methanol extracts obtained from 13 Chinese traditional medicines showed remarkable choleretic effects in normal rats. This paper examines the protective effects against experimental cholestasis induced by carbon tetrachloride (CCl4) or alpha-naphthylisothiocyanate (ANIT) in rats. No medicines, including sodium dehydrocholate and 1-phenylpropanol which are used clinically as choleretic drugs, inhibited the decrease of bile flow induced by CCl4. On the other hand, Intinko-to, Saiko-seikan-to and Bohu-tusyo-san revealed marked improvement of the dysfunction in bile secretion induced by ANIT. These three medicines inhibited the decrease of excretion of bile acid or bilirubin in the bile. They also exerted a protective effect against the alterations of serum components induced by ANIT, i.e., of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and the concentration of serum bilirubin. These results indicate that methanol extracts of Intinko-to, Saiko-seikan-to and Bohu-tusyo-san demonstrate not only choleretic effects but also improvement of cholestasis and liver parenchymal injury in rats.     

Pharmacokinetics of [6]-gingerol after intravenous administration in rats with acute renal or hepatic failure.

The pharmacokinetics of [6]-gingerol were investigated in rats with acute renal failure induced by bilateral nephrectomy, or those with acute hepatic failure induced by a single oral administration of carbon tetrachloride (CCl4), to clarify the contribution of the kidney and liver to the elimination process of [6]-gingerol. After bolus intravenous administration, a plasma concentration-time curve of [6]-gingerol was illustrated by a two-compartment open model. There was no significant difference in either the plasma concentration-time curve or any pharmacokinetic parameters between the control and nephrectomized rats. It is suggested, therefore, that renal excretion does not contribute at all to the disappearance of [6]-gingerol from plasma in rats. In contrast, hepatic intoxication with CCl4 elevated the plasma concentration of [6]-gingerol at the terminal phase. Its elimination half-life increased significantly, from 8.5 to 11.0 min, in CCl4-intoxicated rats. The extent of [6]-gingerol bound to serum protein was more than 90% and was affected very slightly by the CCl4-intoxication. These aspects indicate that [6]-gingerol is eliminated partly by the liver.     

Effect of β-carotene on immunity function and tumour growth in hepatocellular carcinoma rats

The aim of the present study was to investigate the anticancer and immunity activity of β-carotene in hepatocellular carcinoma (HCC) rats. Three days after transplantation, forty Wistar rats were randomly divided into four groups, each group consisting of 10 animals. These groups were control group (untreated), low-dose β-carotene-treated group (20 mg/kg), middle-dose group (40 mg/kg) and high-dose (60 mg/kg) group. β-Carotene-treated groups were fed with β-carotene (20, 40, 60 mg/kg b.w.) orally for 30 days. Control group was treated with the same volume of physiological saline. Another ten rats were served as the normal group. Results showed that 30 days of β-carotene treatment could significantly inhibit tumour growth, enhance blood NK, IL-2, TNF-α, WBC, TP, ALB and A/G levels, and decrease blood ALT, AST and ALP activities in HCC rats. Pathological analysis of liver tissue showed that β-carotene treatment may decrease damage of liver tissue in HCC rats. It can be concluded that β-carotene may improve the immunity function and inhibit tumour growth in HCC rats.     

高硒及高硒高维生素E合用对十二月龄大鼠血清MDA和ALT的影响

给动物喂食高Se、高vitaminE、高Se高vitaminE合用饲料 ,探讨单独及合用高Se、高vitaminE对十二月龄动物血清中MDA和ALT的影响。结果显示 ,与对照组比较 ,单独及合用高Se、高vitaminE均可显著降低血清中MDA的含量 (P <0 0 1 ) ,高vitaminE尚能使血清中ALT水平升高 (P <0 0 5 ) ,而高Se高vitaminE合用则可纠正高vitaminE引起的血清中ALT水平的升高     

Relation between blood clearance and hepatic uptake of 99mTc-phytate in rats with hepatic injury

The relation among the blood clearance of 99mTc-phytate (99mTc-P), the hepatic uptake of 99mTc-P and the severity of hepatic injury was investigated by using the rats with carbon tetrachloride (CCl4), D-galactosamine (Gal N), alpha-naphthylisothiocyanate (ANIT) or DL-ethionine (EthN) induced hepatic injury. After the administration of CCl4, GalN or ANIT, serum GPT activity increased significantly with the increase of dose level, and the degree of this increase was in the order: GalN greater than CCl4 greater than ANIT. However, the mild increase in serum GPT activity was observed after EthN administration. The blood clearance rate of 99mTc-P and the hepatic uptake ratio of 99mTc-P decreased with the increase of dose level after CCl4, GalN or ANIT administration, but significant changes were not found after EthN administration. The degree of decrease in the blood clearance rate of 99mTc-P was in the order: GalN not equal to CCl4 greater than ANIT, and the degree of decrease in the hepatic uptake ratio of 99mTc-P was in the order: GalN not equal to CCl4 greater than ANIT. These results suggest that the disorder in the hepatocytes may be one of causes for inducing the decrease in the hepatic uptake of 99mTc-P, and the consequence of this decrease may induce the decrease in the blood clearance of 99mTc-P.     

Green biosynthesis of Pt-nanoparticles from Anbara fruits: Toxic and protective effects on CCl4 induced hepatotoxicity in Wister rats

Platinum Nanoparticles (PtNPs) are synthesized from the Anbara fruit (Phoenix dactylifera L.) and are characterized using various spectroscopic analytical methods. These PtNPs were used to study the Hepatotoxic and Hepatoprotective effects on acute liver damage caused by CCl₄ in Wister rats. Seventy-two rats of both sexes are divided into twelve groups and are treated with PtNPs and aqueous Anbara extract (AAE). Histopathological examinations were performed to identify the toxic effects on the vital organs of the rats. Hepatoprotective activity was monitored by observing the serobiochemical and hematological parameters and the intensity of hepatic marker enzymes alanine transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP) in the organs such as liver, intestine and kidney. Considerable experimental results were obtained when compared with the standard drug Silymarine. The PtNPs and AAE were proven to have protective activity of enzymes in the liver of Wister rats.     

Chemical constituents and protective effect of Ficus ingens (Miq.) Miq. on carbon tetrachloride-induced acute liver damage in male Wistar albino rats

The aim of the present study was to investigate the chemical constituents and hepatoprotective effect of Ficus ingens (Miq.) Miq. (Moraceae) extract against carbon tetrachloride-induced acute liver damage in male Wistar albino rats. The ethanol extract of F. ingens, was subjected to phytochemical study. In addition, its acute and sub-chronic toxicities were assessed. Eight compounds were isolated from this plant and identified as β-sitosterol, β-sitosterol glucoside, chryasophanol, 7-hydroxy-2,5 dimethyl chromen-4-one, quercetin, Aloe emodin glucoside, rutin and Patuletin-3′-O-methyl-3-O-rutinoside. The structure elucidation was based on ¹H and ¹³C NMR, proton–proton correlation spectroscopy (¹H–¹H Cosy), distortionless enhancement by polarization transfer (DEPT), Heteronuclear Multiple-Quantum Correlation (HMQC), and heteronuclear multiple bond correlations spectrum (HMBC). Hepatotoxicity induced with CCl₄ was evidenced by elevation of liver marker enzymes (ALT, AST, ALP and LDH) and TB content in serum. In addition, antioxidant enzymes were drastically inhibited with significant reduction of GSH and increased LPO in liver homogenate of CCl₄-intoxicated rats. Pre-treatment with F. ingens (200 and 400 mg/kg) and silymarin (50 mg/kg) avoided the changes observed in CCl₄-intoxicated rats. In conclusion, the ethanol extract of F. ingens showed protective activity against liver injury, which might be developed into a new hepatoprotective agent.     

Protective Role of Quercetin in Carbon Tetrachloride Induced Toxicity in Rat Brain: Biochemical,Spectrophotometric Assays and Computational Approach

Carbon tetrachloride (CCL4) induces oxidative stress by free radical toxicities, inflammation, and neurotoxicity. Quercetin (Q), on the other hand, has a role as anti-inflammatory, antioxidant, antibacterial, and free radical-scavenging. This study explored protection given by quercetin against CCL4 induced neurotoxicity in rats at given concentrations. Male Wistar rats were divided into four groups Group C: control group; Group CCL4: given a single oral dose of 1 mL/kg bw CCL4; Group Q: given a single i.p injection of 100 mg/kg bw quercetin; and Group Q + CCL4: given a single i.p injection of 100 mg/kg bw quercetin before two hours of a single oral dose of 1 mL/kg bw CCL4. The results from brain-to-body weight ratio, morphology, lipid peroxidation, brain urea, ascorbic acid, reduced glutathione, sodium, and enzyme alterations (aspartate aminotransferase (AST), alanine aminotransferase (ALT), catalase, and superoxide dismutase) suggested alterations by CCL4 and a significant reversal of these parameters by quercetin. In silico analysis of quercetin with various proteins was conducted to understand the molecular mechanism of its protection. The results identified by BzScore4 D showed moderate binding between quercetin and the following receptors: glucocorticoids, estrogen beta, and androgens and weak binding between quercetin and the following proteins: estrogen alpha, Peroxisome proliferator-activated receptors (PPARγ), Herg k+ channel, Liver x, mineralocorticoid, progesterone, Thyroid α, and Thyroid β. Three-dimensional/four-dimensional visualization of binding modes of quercetin with glucocorticoids, estrogen beta, and androgen receptors was performed. Based on the results, a possible mechanism is hypothesized for quercetin protection against CCL4 toxicity in the rat brain.