Effect of ascorbic acid supplementation on liver and kidney toxicity in cyclophosphamide-treated female albino rats.

Effects of ascorbic acid supplementation on the activity of acid phosphatase (ACP), alkaline phosphatase (ALP), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) on liver, kidney and serum in cyclophosphamide-treated female virgin rats were investigated. Oral administration of cyclophosphamide at the dose of 5 mg/kg body weight/day for 12 days resulted in a significant elevation in ACP and ALP activities in liver, kidney and serum. Ascorbic acid supplementation at the dose of 25 mg/kg body weight/day showed a significant protection in the activity of ACP in liver, kidney and serum, but only in ALP activity in kidney. ALP activities in liver and serum were not restored to control level by ascorbic acid supplementation. Activities of GOT and GPT were elevated significantly in liver, kidney and serum after cyclophosphamide treatment, and were protected and restored to control level by ascorbic acid supplementation.     

Antioxidant and hepatoprotective activity of Cordia macleodii leaves

This investigation was undertaken to evaluate ethanolic extract of Cordia macleodii leaves for possible antioxidant and hepatoprotective potential. Antioxidant activity of the extracts was evaluated by four established, in vitro methods viz. 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging method, nitric oxide (NO) radical scavenging method, iron chelation method and reducing power method. The extract demonstrated a significant dose dependent antioxidant activity comparable with ascorbic acid. The extract was also evaluated for hepatoprotective activity by carbon tetrachloride (CCl₄) induced liver damage model in rats. CCl₄ produced a significant increase in levels of serum glutamate pyruvate transaminase (GPT), serum glutamate oxaloacetate transaminase (GOT), Alkaline Phosphatase (ALP) and total bilirubin. Pretreatment of the rats with ethanolic extract of C. macleodii (100, 200 and 400 mg/kg po) inhibited the increase in levels of GPT, GOT, ALP and total bilirubin and the inhibition was comparable with Silymarin (100 mg/kg po). The present study revealed that C. macleodii leaves have significant radical scavenging and hepatoprotective activities.     

Studies on protective effect of Cyperus Scariosus extract on acetaminophen and CCl4-induced hepatotoxicity

• 1.1. The hepatoprotective activity of aqueous-methanolic extract of Cyperus scariosus (Cyperaceae) was investigated against acetaminophen and CCl₄-induced hepatic damage.
• 2.2. Acetaminophen produced 100% mortality at a dose of 1 g/kg in mice while pretreatment of animals with plant extract (500 mg/kg) reduced the death rate to 30%.
• 3.3. Acetaminophen at a dose of 640 mg/kg produced liver damage in rats as manifested by the rise in serum levels of alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) to 430 ± 68, 867 ± 305 and 732 ± 212 IU/1 (n = 10) respectively, compared to respective control values of 202 ± 36, 59 ± 14 and 38 ± 7.
• 4.4. Pretreatment of rats with plant extract (500 mg/kg) significantly lowered (P < 0.05) the respective serum ALP, GOT and GPT levels to 192 ± 31, 63 ± 9 and 35 ± 8.
• 5.5. The hepatotoxic dose of CCl₄ (1.5ml/kg; orally) raised serum ALP, GOT and GPT levels to 328 ± 30, 493 ± 102 and 357 ± 109 IU/1 (n = 10) respectively, compared to respective control values of 177 ± 21, 106 ± 15 and 47 ± 12.
• 6.6. The same dose of plant extract (500 mg/kg) was able to significantly prevent (P < 0.05) CCl₄-induced rise in serum enzymes and the estimated values of ALP, GOT and GPT were 220 ± 30, 207 ± 95 and 75 ± 38, respectively.
• 7.7. The plant extract also prevented CCl₄-induced prolongation in pentobarbital sleeping time confirming hepatoprotectivity.
• 8.8. These results indicate that the Cyperus scariosus possesses hepatoprotective activity and thus, rationalizes the folkloric use of this plant in hepato-biliary disorders.

     

The effects of fucoidan extracts on CCl<Subscript>4</Subscript>-induced liver injury

The aim of this study was to elucidate the antioxidant properties of fucoidan extracts (FE) against CCl(4)-induced oxidative stress by monitoring the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Female, Sparague-Dowley rats were administered with FE (100 mg/kg daily) for 14 days and CCl(4) on the 15'th day, 12 h before they were sacrificed. The levels of GOT, GPT, ALP and LDH in serum of rats, as well as the levels of MDA, SOD, CAT and GPx in total liver homogenate were analyzed. CCl(4)-treatment was found to increase the levels of GOT, GPT, ALP, LDH and MDA, as well as decrease levels of SOD, CAT and GPx significantly. The pre-treatment of rats with FE, however, suppressed the increment of levels of GOT, GPT, ALP, LDH and MDA, as well as recovered the levels of SOD, CAT and GPx in CCl(4)-treated rats. Moreover there was a significant decrease in incidences of necrosis and cirrhosis in the liver tissue of FE-treated rats. These results implied that FE possessed antioxidant properties against CCl(4)-induced oxidative stress.     

Semen Hoveniae extract protects against acute alcohol-induced liver injury in mice

The protective effects of Semen Hoveniae extract (SHE) from Hovenia dulcis Thunb. (Rhamnaceae) on acute alcohol-induced liver injury were investigated in vivo using mice as test models. In the present study, SHE (150, 300, 600?mg/kg/day) was given to mice by intragastric administration for 4 days. Mice were gavaged with 60% ethanol 10?mL/kg after the last dose of extract. Six hours after alcohol administration, liver injury was evaluated by biochemical examination. Lipid peroxidation and the activity of antioxidants were measured by spectrophotometric methods. In mice, administration of SHE significantly decreased the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum. Administration of SHE also protected against alcohol-induced alcohol dehydrogenase (ADH) elevation in mice. Concurrently, there was an augmentation in the activities of antioxidant enzymes such as superoxide dismutase (SOD), glutathione S-transferase (GST), and glutathione (GSH), and it also facilitated alcohol metabolism. Acute toxicity tests showed that a single dose of oral SHE up to 22?g/kg did not result in any death or toxic side effects in mice during 14 days’ observation. These results demonstrate that SHE could protect against acute alcohol-induced liver injury without any toxic side effects. Therefore, Semen Hoveniae has potential for the development of a clinically useful agent which could protect the liver from alcohol-induced injury.     

bFGF对慢性酒精中毒大鼠血清GPT、GOT活性的影响

目的：观察碱性成纤维细胞生长因子（bFGF）对慢性酒精中毒大鼠血清GPT、GOT活性的影响,探讨bFGF对酒精中毒所致的肝损伤是否具有保护作用。方法：选择成年Wistar雄性大鼠,采用白酒灌胃建立慢性酒精中毒模型,慢性酒精中毒模型建立成功的大鼠采用随机抽签法分为酒精中毒对照组、NS对照组和bFGF治疗组。另10只不灌白酒作为正常对照组。bFGF治疗组大鼠白酒灌胃的同时,1h后按12μg/kg剂量肌内注射,共14d。各组大鼠到相对应的时间点取血测定血清谷丙转氨酶（GPT）、谷草转氨酶（GOT）活性。结果：慢性酒精中毒后大鼠血清GPT、GOT活性比正常对照组均明显升高（P〈0.01）,用bFGF治疗酒精中毒大鼠后血清GPT、GOT活性均明显下降（P〈0.01）。结论：bFGF能降低酒精中毒大鼠后血清GPT和GOT活性,对酒精中毒所致的肝损伤具有保护作用。     

联苯双酯对小鼠肝损伤保护作用的进一步研究

本研究证明:联苯双酯不仅能降低四氯化碳引起的小鼠血清谷丙转氨酶(以下简称SGPT)水平升高,对肝脏病理损害亦有明显的保护作用。此外,还发现联苯双酯能使正常小鼠、四氯化碳肝损伤小鼠及强的松龙处理的小鼠肝组织中GPT降低,但对谷草转氨酶(GOT)及醛缩酶活性无明显影响。在使正常小鼠肝脏GPT活性明显降低时,心脏GPT活性无明显变化。联苯双酯对四氯化碳引起的小鼠SGPT升高的降低作用似非直接抑制血清及肝组织中的GPT活性,或促进血液中GPT的消失。     

Effect of SKF525-A on the glutathione-conjugating enzyme system and on liver toxicity

SKF525-A given intraperitoneally (50 mg/kg body weight) to Sprague-Dawley rats in a single dose promoted a significant reduction in cytosolic glutathione S-transferase (GST) activities 0.5 and 1 h after injection. There was no decrease in liver non-protein sulfhydryls (NPSH) 0.5, 1 and 24 h after injection. Serum activities of glutamic pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), glutamic oxaloacetic transaminase (GOT) and glutamate dehydrogenase (GLDH) increased 1.8-, 2.9-, 3.8- and 41.2-fold respectively 8 h after injection, and the increased serum enzyme activities were maintained for up to 24 h. On the basis of these results, SKF525-A-induced blood manifestations of liver toxicity and decrease in GST activities may be regarded as confusing factors in the evaluation of the oxidative metabolism of compounds in Sprague-Dawley rats.     

Effects of exogenous vitamin C on ethanol toxicity in rats

The effect of a mega dose of ascorbic acid (200 mg/100 g body wt.) on alcohol-induced toxicity in rats was evaluated. In rats administered alcohol and ascorbic acid, malondialdehyde (MDA), hydroperoxide and conjugated dienes decreased in comparison with that given alcohol alone. The reduced activities of scavenging enzymes, e.g. superoxide dismutase (SOD) and catalase, in ethanol-administered rats were also enhanced by the co-administration of ascorbic acid and ethanol. Co-administration of ethanol and ascorbic acid reduced phospholipids and MDA levels of the erythrocyte membrane in comparison with that of the ethanol fed rats. The reduction in the activities of glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), gamaglutamyl transpeptidase (GGT) and the decrease in triglycerides levels also clearly showed the protective action of ascorbic acid in reducing ethanol induced toxicity.     

Effects of N-acetyl cysteine on oxidative stress and TNF-α gene expression in diclofenac-induced hepatotoxicity in rats

The consumption of non-steroidal anti-inflammatory drug, such as diclofenac, can lead to hepatotoxicity. In the present study, protective effect of N-acetyl cysteine (NAC) on diclofenac-induced hepatotoxicity was investigated. Thirty-two male rats were divided into four groups. Group 1 (control group) was treated with normal saline (1?ml/kg, i.p.) for 4?d. Group 2 (test without treatment) received diclofenac only (50?mg/kg, i.p.) for 4?d. Groups 3 and 4 received diclofenac (50?mg/kg, i.p.) plus NAC (150?mg/kg, p.o) and silymarin (100?mg/kg, p.o) for 4?d, respectively. At the end of experiment, serum glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), alkaline phosphatase (ALP), lipid profile, uric acid, protein carbonyl content, MDA, liver TNF-α, ferric-reducing antioxidant power, liver catalase, superoxide dismutase, vitamin C, and histopathological examination were done. In group 2, diclofenac caused a significant increase (p?TNF-α gene expression as opposed to group 1. In treated groups with NAC and silymarin, a significant reduction (p?相似文献   

酒精性肝损伤大鼠细胞色素P450 CYP2E1和细胞色素P450 CYP3A的代谢活性

目的观察酒精性肝损伤对大鼠细胞色素P450CYP3A(CYP3A)和细胞色素P450CYP2E1(CYP2E1)代谢活性的影响。方法采用ig给予白酒制备大鼠酒精性肝损伤模型,检测血清中谷丙转氨酶(GPT)和谷草转氨酶(GOT)活性,采用HE染色法光镜下观测酒精对肝脏损伤程度。大鼠ip给予CYP3A探针药物咪达唑仑10mg·kg-1或ig给予CYP2E1探针药物氯唑沙宗50mg·kg-1后,采用高效液相色谱法测定不同时间点大鼠血浆中咪达唑仑和氯唑沙宗的血药浓度,并应用3P87软件计算其药代动力学参数,以考察CYP2E1和CYP3A的代谢活性的变化。大鼠ig给予氯唑沙宗80mg·kg-1后,热板方法测定大鼠添足次数和添足反射潜伏期。结果酒精性肝损伤可致大鼠肝小叶结构不清,肝索排列紊乱,肝细胞体积增大,呈弥漫性中度水变性,肝窦受压,大部分肝细胞胞浆内见大小不等的脂肪空泡;与正常对照组相比,酒精性肝损伤组大鼠GPT和GOT活性分别增加了16.0%和20.0%(P<0.05,P<0.01)。酒精性肝损伤致大鼠CYP2E1对探针药物氯唑沙宗的代谢活性增强,AUC,t1/2和cmax分别降低了38.0%,30.5%和35.0%(P<0.05);酒精肝损伤组大鼠氯唑沙宗镇痛效果明显降低;酒精性肝损伤致大鼠CYP3A对探针药物咪达唑仑的代谢活性增强,AUC,t1/2和cmax分别降低了122.6%,54.9%和56.9%(P<0.01,P<0.05)。结论酒精性肝损伤可使大鼠CYP2E1和CYP3A代谢活性增强。     

Effect of glycine on tissue fatty acid composition in an experimental model of alcohol-induced hepatotoxicity

1. The aim of the present study was to investigate the effect of the administration of glycine, a non-essential amino acid, on blood alcohol levels and tissue fatty acid composition in experimental rats. 2. Liver cell damage was induced by the administration of ethanol (7.9 g/kg bodyweight) for 30 days by intragastric intubation. Control rats were given isocaloric glucose solution. Glycine was subsequently administered at a dose of 0.6 g/kg bodyweight every day by intragastric intubation for the next 30 days. 3. Feeding alcohol significantly elevated the activities of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatases (ALP) and gamma-glutamyl transpeptidase (GGT) and altered the liver and brain fatty acid composition compared with control rats. Subsequently, glycine supplementation to alcohol-fed rats significantly lowered the activities of serum AST, ALT, ALP, GGT and normalized the liver and brain fatty acid composition compared with untreated alcohol-fed rats. 4. Thus, the present study demonstrates that oral administration of glycine confers a significant protective effect against alcohol-induced hepatotoxicity by virtue of its ability to optimize the activities of serum AST, ALT, ALP and GGT, as well as the tissue fatty acid composition.     

Liver injury model in mice for immunopharmacological study

Experimental liver injury was produced in mice by the immunological technique. The utility of these models as an immunopharmacological method was investigated. The first model was produced by the injection of anti-basic liver protein (BLP) rabbit antibody into DBA/2 mice that had been previously immunized with rabbit IgG. The second liver injury was caused by injection of anti-liver specific protein (LSP) rabbit antibody into DBA/2 mice. The third model was produced by the injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated ddY mice. In all injury models, extensive liver parenchymal cell damage was estimated by elevation of glutamate transaminase (GOT and GPT) activity. These were confirmed by histopathological studies of the liver. Typical histopathological changes in the liver from injured mice were submassive hepatocellular necrosis and infiltration of granulocytes and lymphocytes into the portal tract and sinusoid in the necrotic lesion. Administration of prednisolone and cyclophosphamide for 10 days prior to injection of eliciting antibodies or LPS suppressed the elevation of serum transaminase levels in all experimental liver injury models. Cianidanol and sylibin inhibited the elevation of GOT and GPT in anti-BLP induced liver injured mice. These evidences suggest that the above models are suitable for investigating the remedy for liver diseases.     

Protection from acetaminophen-induced liver damage by the synergistic action of low doses of the poly(ADP-ribose) polymerase-inhibitor nicotinamide and the antioxidant N-acetylcysteine or the amino acid l-methionine

• 1.1. An array of therapeutically used analgetic and antirheumatic drugs cause severe liver damage. The present study investigates the hepatoprotective effects of inhibitors of NAD-dependent adenoribosylation reactions and of antioxidants in analgesic-induced hepatic injury.
• 2.2. Male NMRI mice were treated PO with 500 mg/kg of acetaminophen, and the activities of both glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) were determined in serum.
• 3.3. The acetaminophen-induced release of both GOT and GPT from injured liver cells could be inhibited in a dose-dependent manner, when mice were injected additionally either with increasing amounts (from (25 mg/kg to 100 mg/kg IP) of the PARP-inhibitor nicotinamide, with increasing amounts (from 25 mg/kg to 100 mg/kg IP) of the antioxidant N-acetylcysteine, or with increasing amounts (from 50 mg/kg to 300 mg/kg IP) of the amino acid l-methionine.
• 4.4. A combination of both nicotinamide and N-acetylcysteine (at the low dose of 12.5 mg/kg IP each) results in a complete protection from acetaminophen-induced release of GOT and GPT from injured liver cells.
• 5.5. A combination of both L-methionine and N-acetylcysteine or nicotinamide (at the low dose of 12.5 mg/kg IP each) resulted also in complete protection from acetaminophen-induced release of GOT and GPT.

     

Hepatoprotective activity of Andrographis Paniculata and Swertia Chirayita

Andrographis paniculata (Family: Acanthaceae) and Swertia chirayita (Family: Gentianaceae) are two controversial medicinal plants used as Kiriyattu, having similar therapeutic action and are used as a hepatoprotective and hepatostimulative agent. A. paniculata grows in southern parts of India and S. chirayita in the Himalayan region. The present work concerns on the ability of the extracts of these plants to offer protection against acute hepatotoxicity induced by paracetamol (150 mg/kg) in Swiss albino mice. Oral administration of A. paniculata or S. chirayita extract (100–200 mg/kg) offered a significant dose dependent protection against paracetamol induced hepatotoxicity as assessed in terms of biochemical and histopathological parameters. The paracetamol induced elevated levels of serum marker enzymes such as serum glutamate pyruvate transaminase (GPT), serum glutamate oxaloacetate transaminase (GOT), alkaline phosphatase (ALP), and bilirubin in peripheral blood serum and distorted hepatic tissue architecture along with increased levels of lipid peroxides (LPO) and reduction of superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and glutathione peroxidase (GPx) in liver tissue. Administration of the plant extracts after paracetamol insult restored the levels of these parameters to control (untreated) levels. Thus the present study revealed that the extracts of A. paniculata or S. chirayita offered protection against hepatotoxicity induced by paracetamol.     

Acute nephrotoxicities and hepatotoxicities of 1,2-dibromo-3-chloropropane and 1,2-dibromoethane in male and female F344 rats

Four consecutive intraperitoneal (i.p.) injections with 40 mg/kg of 1,2-dibromo-3-chloropropane (DBCP) reduced the in vitro accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA) by slices of renal cortex and increased blood urea nitrogen (BUN) concentration in both male and female rats, but elevated serum glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) activities in females only. Four consecutive treatments with 1,2-dibromoethane (EDB) reduced the accumulation of PAH in male rats, but failed to alter TEA accumulation, BUN concentration or GPT and GOT activities in rats of either sex. Single i.p. injections of EDB or DBCP (40 mg/kg, approximately one-half of the acute, i.p. LD50 values) were without effect on serum GPT and GOT activities, BUN concentration or the accumulations of PAH and TEA in male rats when measured 24, 48 or 96 h after treatment, except that PAH accumulation was reduced at 96 h.These results indicate that BUN and the accumulations in vitro of PAH and TEA by renal cortical slices are appropriate endpoints for studying DBCP nephrotoxicity. Measurements of serum GOT and GPT activities detected DBCP hepatotoxicity in female rats only. The nephrotoxicity of EDB was indicated by measurement of TEA accumulation only.     

The influence of antagonists of poly(adp-ribose) metabolism on acetaminophen hepatotoxicity

An array of therapeutically used analgetic and antirheumatic drugs causes severe liver damage. The present study investigates the hepatoprotective effects of inhibitors of NAD-dependent adenoribosylation reactions in analgesics-induced hepatic injury. Male NMRI mice were treated perorally with 500 mg/kg of acetaminophen, and the activities of both glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) were determined in serum. In addition, the activity of poly(ADP-ribose)polymerase (PARP) was quantified in liver cell nuclei. While the PARP-activity remained essentially unchanged, the acetaminophen-induced release of both GOT and GPT from injured liver cells could be inhibited by 90–99%, when mice were injected additionally with the selective PARP-inhibitors nicotinic acid amide, benzamide, caffeine, theophyline, and thymidine, respectively. We see the main application of inhibitors of adenoribosylation reactions as for the combinational use in pharmaceutical preparations of analgesics and antirheumatic drugs in order to avoid hepatic damage.     

Chemoprevention of N-nitrosodiethylamine induced phenobarbitol promoted liver tumors in rat by extract of Indigofera aspalathoides

The chemopreventive effect of ethanol extract of Indigofera aspalathoides (EIA) on N-nitrosodiethylamine (DEN, 200 mg/kg)-induced experimental liver tumor was investigated in male Wistar rats. Oral administration of ethanol extract of Indigofera aspalathoides (250 mg/kg) effectively suppressed liver tumor induced with DEN as revealed by decrease in the levels of extend of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO), glutathione peroxidase (Gpx) and glutathione S-transferase (GST) with a concomitant increase in enzymatic antioxidant (superoxide dismutase and catalase) levels when compared to those in liver tumor bearing rats. The histopathological changes of liver sample were compared with respective control. Our results show a significant chemopreventive effect of EIA against DEN induced liver tumor.     

Effect of repeated dermal application of endosulfan to rats

Dermal application of endosulfan to male (18.75, 37.50 and 62.50 mg/kg/day) and female (9.83, 19.66 and 32.0 mg/kg/d) rats for 30 days produced hyperexcitability, tremor, dyspnea and salivation. There were no deaths. The signs of toxicity subsided after a week. Endosulfan produced no significant changes in the organ:body weight ratio. No significant changes were seen in the histological and hematological indices. However, a significant decrease in liver GOT and GPT and serum GPT activities and a significant rise in serum alkaline phosphatase and total protein were recorded in the endosulfan-treated animals. There were no changes in LDH. Residue analysis revealed higher levels of total endosulfan in fatty tissues of rats receiving the highest dose of endosulfan.     

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.