<Emphasis Type="Italic">Undaria pinnatifida</Emphasis> fucoidan extract protects against CCl<Subscript>4</Subscript>-induced oxidative stress

This study was performed to elucidate the effects of Undaria pinnatifida fucoidan extract (UPFE) in preventing CCl₄-induced oxidative stress. UPFE (100 mg/kg) was intraperitoneally administered to rats for 14 days. On day 15, CCl₄ dissolved in olive oil (50% CCl₄) was injected 12 h before they were anesthetized and dissected. To measure UPFE-mediated antioxidation, we examined the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in serum, as well as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in liver homogenates. CCl₄ treatment markedly increased the levels of GOT, GPT, ALP, LDH, and MDA and significantly decreased levels of SOD, CAT, and GPx. UPFE pretreatment decreased levels of GOT, GPT, ALP, LDH, and MDA, by 62.8, 68.5, 41.9, 72.7, and 122%, respectively and increased those of SOD, CAT, and GPx by 111.1, 15.9, and 52.6%, respectively. These results showed that UPFE has antioxidant effects against CCl₄-induced oxidative stress.     

The effect of carbon tetrachloride on isolated rat hepatocytes

Isolated rat hepatocytes were incubated with carbon tetrachloride (CCl4) at a concentration of 0.2 mol CCl4/ml of incubation medium. The ultrastructural alterations and release of lactate dehydrogenase (LDH) and glutamate-oxaloacetate transaminase (GOT), were recorded after different periods of incubation. After 5 min incubation with CCl4, morphological changes observed by electron microscopy, involved the plasma membrane. The endoplasmic reticulum and mitochondria were altered later. These morphological alterations were accompanied by an early release of LDH and GOT into the incubation medium. It is concluded that, in contrast with its in vivo effects, in vitro CCl4 can induced an early morphological alteration of the hepatocyte plasma membrane before damaging the endoplasmic reticulum.     

A comparative study of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels in the saliva of diabetic and normal patients

Diabetes has been reported to affect salivary glands adversely in humans and experimental models. Glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) are salivary enzymes that also are widely distributed in animal tissues. We determined GOT and GPT levels in saliva samples of 100 type 1 and 30 type 2 diabetic patients using reflectance spectrophotometry and compared them to 30 age and sex matched healthy controls. Statistically significant differences were observed in the mean values of GOT and GPT in type 1 diabetics compared to type 2 and control groups. Significantly higher GOT levels were found in the 1–20 year age group of type 1 diabetics. Our findings suggest that salivary gland damage is due to the same immunological attack that affects pancreatic β cells and results in type 1 diabetes.     

Protective effects of hepatocyte-specific glycyrrhetic derivatives against carbon tetrachloride-induced liver damage in mice

Glycyrrhetic acid (GA), the main hydrolysate of glycyrrhizic acid extracted from the roots of the Chinese herb Glycyrrhiza glabra, was reported to be accumulated in hepatocytes due to the extensive distribution of GA receptors in liver. A series of hepatocyte-specific derivatives on the basis of anetholtrithione and glycyrrhizic were designed and synthesized. The potential beneficial effect was evaluated in carbon tetrachloride (CCl₄)-induced liver injury model. In addition, the hepatoprotective activity of these derivatives was assessed by measuring levels of serum marker enzymes, including serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT), alkaline phosphatase (AKP), lactate dehydrogenase (LDH) and the ratio of GSH to GSSG. Gratifyingly, compounds 5a–c (100 mg/kg, p.o.) markedly prevented CCl₄-induced elevation of levels of serum GPT, GOT. A comparative histopathological study of liver exhibited almost a normal liver lobular architecture and cell structure of the livers, as compared to CCl₄-treated group. These findings were confirmed with the histopathological observations, where hepatocyte-specific glycyrrhetic acid derivatives 5a–c were capable of reversing the toxic effects of CCl₄ on hepatocytes.     

Hepatoprotective Effect of Arctium lappa Root Extract on Cadmium Toxicity in Adult Wistar Rats

This study was performed to determine the effects of Arctium lappa (Al) to protect against cadmium damage in the rat liver. Male rats received a single i.p. dose of CdCl₂ (1.2 mg/kg body weight (BW)) with or without Al extract administered daily by gavage (300 mg/kg BW) for 7 or 56 days. After 7 days, Al caused plasma transaminase activity to diminish in groups Al (glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT)) and CdAl (GPT). After 56 days, GOT and GPT plasma activities were reduced in the Cd group. No alteration in plasma levels of creatinine, total bilirubin, and total protein were observed. GOT liver activity increased in the Cd group. No alteration was observed in superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and malondialdehyde (MDA) dosage. In the Cd group, hepatocyte proportion decreased and sinusoid capillary proportion increased. In the Al and CdAl groups, the nuclear proportion increased and the cytoplasmic proportion decreased. The hepatocyte nucleus density reduced in Cd and increased in the Al group. After 56 days, there was no alteration in the Cd group. In Al and CdAl groups, the nuclear proportion increased without cytoplasmic proportion variation, but the sinusoid capillary proportion was reduced. The hepatocyte nucleus density decreased in the Cd group and increased in the Al and CdAl groups. In conclusion, the liver function indicators showed that A. lappa protected the liver against cadmium toxicity damage.     

Pharmacokinetics of Glutamate–Oxaloacetate Transaminase and Glutamate–Pyruvate Transaminase and Their Blood Glutamate-Lowering Activity in Na?ve Rats

Traumatic brain injury (TBI) and stroke lead to elevated levels of glutamate in the brain that negatively affect the neurological outcomes in both animals and humans. Intravenous administration of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) enzymes can be used to lower the blood glutamate levels and to improve the neurological outcome following TBI and stroke. The objective of this study was to analyze the pharmacokinetics and to determine the glutamate-lowering effects of GOT and GPT enzymes in na?ve rats. We determined the time course of serum GOT, GPT, and glutamate levels following a single intravenous administration of two different doses of each one of the studied enzymes. Forty-six male rats were randomly assigned into one of 5 treatment groups: saline (control), human GOT at dose 0.03 and 0.06?mg/kg and porcine GPT at dose 0.6 and 1.2?mg/kg. Blood samples were collected at baseline, 5?min, and 2, 4, 8, 12, and 24?h after the drug injection and GOT, GPT and glutamate levels were determined. The pharmacokinetics of both GOT and GPT followed one-compartment model, and both enzymes exhibited substantial glutamate-lowering effects following intravenous administration. Analysis of the pharmacokinetic data indicated that both enzymes were distributed predominantly in the blood (central circulation) and did not permeate to the peripheral organs and tissues. Several-hour delay was present between the time course of the enzyme levels and the glutamate-lowering effects (leading to clock-wise hysteresis on concentration-effect curves), apparently due to the time that is required to affect the pool of serum glutamate. We conclude that the interaction between the systemically-administered enzymes (GOT and GPT) and the glutamate takes place in the central circulation. Thus, glutamate-lowering effects of GOT and GPT apparently lead to redistribution of the excess glutamate from the brain's extracellular fluid into the blood and can reduce secondary brain injury due to glutamate neurotoxicity. The outcomes of this study regarding the pharmacokinetic and pharmacodynamic properties of the GOT and GPT enzymes will be subsequently verified in clinical studies that can lead to design of effective neuroprotective treatment strategies in patients with traumatic brain diseases and stroke.     

The effects of thromboxane A2 inhibitors (OKY-046 and ONO-3708) and leukotriene inhibitors (AA-861 and LY-171883) on CCl4-induced chronic liver injury in mice

The effects of OKY-046, a selective thromboxane A2 (TxA2) synthetase inhibitor, ONO-3708, a novel TxA2 receptor antagonist, AA-861, a selective 5-lipoxygenase inhibitor and LY-171883, a peptide leukotrienes (p-LTs) receptor antagonist on the chronic liver injury were investigated in mice. The chronic liver injury was induced by the injection of carbon tetrachloride (CCl4) two times a week for twelve weeks in mice. In chronic liver injury models, significant histopathological changes in the liver and extensive elevation of glutamate transaminase (GOT and GPT) activity were observed. Administration of OKY-046, ONO-3708, AA-861 and LY-171883 for 12 weeks suppressed the elevation of serum GOT and GPT levels and histopathological changes in CCl4-induced chronic liver injury. These results suggest that TxA2 and LTs inhibitors are effective for the onset and development of chronic liver injury in mice.     

Effect of Zinc and Iron Fortification of the Feed on Liver and Thyroid Function in Rats

Changes in plasma glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), triiodothyronine (T3), and thyroxin (T4) of male rats, following 8?weeks of administration of different concentrations of elemental iron (EI), sodium iron ethylenediaminetetraacetate (NaFeEDTA), zinc sulfate (ZnSO(4)), and zinc oxide (ZnO) in whole wheat flour were investigated. Liver enzymes and thyroid hormones were determined using colorimetric methods and enzyme immune assay, respectively. Ingestion of fortified diets by the male rats did not show a marked effect on GOT and GPT, the exception being NaFeEDTA fed alone and EI with ZnO-fortified diets indicating a significant (p?相似文献   

Effect of Emblica officinalis (Gaertn) on CCl4 induced hepatic toxicity and DNA synthesis in Wistar rats

A single dose of CCl4 (1 ml/kg body weight, po in corn oil) increased the levels of SGOT (serum glutamate oxaloacetate transaminase), SGPT (serum glutamate pyruvate transaminase), LDH (lactate dehydrogenase), glutathione-S-transferase and depletion in reduced glutathione, glutathione peroxidase and glutathione reductase. It also caused enhancement in the levels of lipid peroxidation (LPO) and DNA synthesis. There was also pathological deterioration of hepatic tissue as evident from multivacuolated hepatocytes containing fat globules around central vein. The pretreatment of E. officinalis for 7 consecutive days showed a profound pathological protection to liver cell as depicted by univacuolated hepatocytes. Pretreatment with E. officinalis at doses of 100 and 200 mg/kg body weight, prior to CCl4 intoxication showed significant reduction in the levels of SGOT, SGPT, LDH, glutathione-S-transferase, LPO and DNA synthesis. There was also increase in reduced glutathione, glutathione peroxidase and glutathione reductase. The results suggest that E. officinalis inhibits hepatic toxicity in Wistar rats.     

Protective effects of sodium nitrite preconditioning against alcohol-induced acute liver injury in mice

The purpose of the present study was to investigate the effect of sodium nitrite (SN) on alcohol-induced acute liver injury in mice. Forty male C57bL/6 mice were randomly divided into 4 groups. Acute alcohol-induced liver injury group were injected intraperitoneal (ip) with alcohol (4.5 g/kg); SN preconditioning group were pretreated with SN (16 mg/kg, ip) for 12 h, and received alcohol (4.5 g/kg, ip) injection; Control and SN groups were treated with saline and SN, respectively. After the treatments, liver index (liver/body weight ratio) was determined. Colorimetric technique was performed to measure the serum alanine transaminase (ALT), aspartate transaminase (AST), liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities, as well as malondialdehyde (MDA) content. The pathological index of liver tissue was assayed by HE and TUNEL fluorometric staining. Using Western blot and immunohistochemistry staining, the expression of hypoxia-inducible factor-1α (HIF-1α) protein was detected. The results showed that, compared with acute alcohol-induced liver injury group, pretreatment with low doses of SN decreased liver index and serum levels of ALT and AST, weakened acute alcohol-induced hepatocyte necrosis, improved pathological changes in liver tissue, increased live tissue SOD, GSH-Px and CAT activities, reduced MDA content and apoptosis index of hepatocytes, and up-regulated HIF-1α protein level in liver tissue. These results suggest that the pretreatment of SN can protect hepatocytes against alcohol-induced acute injury, and the protective mechanism involves inhibition of oxidative stress and up-regulation of HIF-1α protein level.     

Hepatoprotective activity of Hemidesmus indicus R. br. in rats

Treatment of rats with paracetamol and CCl4 produced a significant increase in the levels of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total and direct bilirubin. Rats pretreated with methanolic extract of roots of H. indicus (100-500 mg/kg body weight, po) exhibited rise in the levels of these enzymes but it was significantly less as compared to those treated with paracetamol or CCl4 alone. The results of methanolic extract of H. indicus were comparable with the standard hepatoprotective agent silymarin (100 mg/kg). Maximum hepatoprotective effect was found to be at the dose of 250 mg/kg body weight in case of CCl4 induced hepatic damage while 500 mg/kg body weight in case of paracetamol induced hepatic damage. The results suggest that methanolic extract of H. indicus roots possesses a potential antihepatotoxic activity.     

Hepatoprotective and antioxidant effect of tender coconut water on carbon tetrachloride induced liver injury in rats

Hepatoprotective and antioxidant effects of tender coconut water (TCW) were investigated in carbon tetrachloride (CCl4)-intoxicated female rats. Liver damage was evidenced by the increased levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and decreased levels of serum proteins and by histopathological studies in CCl4-intoxicated rats. Increased lipid peroxidation was evidenced by elevated levels of thiobarbituric acid reactive substance (TBARS) viz, malondialdehyde (MDA), hydroperoxides (HP) and conjugated dienes (CD), and also by significant decrease in antioxidant enzymes activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx) and glutathione reductase (GR) and also reduced glutathione (GSH) content in liver. On the other hand, CCl4-intoxicated rats treated with TCW retained almost normal levels of these constituents. Decreased activities of antioxidant enzymes in CCl4-intoxicated rats and their reversal of antioxidant enzyme activities in TCW treated rats, shows the effectiveness of TCW in combating CCl4-induced oxidative stress. Hepatoprotective effect of TCW is also evidenced from the histopathological studies of liver, which did not show any fatty infiltration or necrosis, as observed in CCl4-intoxicated rats.     

Cardioprotective effect of coconut kernel protein in isoproterenol administered rats

Male albino rats were given subcutaneous injection of isoproterenol (10 mg/100 g body wt) twice at an interval of 24 hr to induce myocardial infarction. The rats showed massive myocardial necrosis and increased activities of creatinine phosphokinase (CPK), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), in serum, while a decrease in nitric oxide synthase activity and lower levels of palmitate oxidation into CO2 and ATP were observed in the heart. Rats pre-treated with coconut protein or L-arginine showed significantly decreased CPK, GOT and GPT activities in the serum. There was significantly higher nitric oxide synthase activity and higher rate of palmitate oxidation into CO2 and increased levels of ATP in the heart in these groups. These observations indicate the cardioprotective effect of coconut protein, which may be attributed to the high content of L-arginine present in it.     

Attenuation of the acute adriamycin-induced cardiac and hepatic oxidative toxicity by N-(2-mercaptopropionyl) glycine in rats

The protective effect of the synthetic aminothiol, N-(2-mercaptopropionyl) glycine (MPG) on adriamycin (ADR) induced acute cardiac and hepatic oxidative toxicity was evaluated in rats. ADR toxicity, induced by a single intraperitoneal injection (15 mg/kg), was indicated by an elevation in the level of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase isoenzyme (CK-MB), and lactic dehydrogenase (LDH). ADR produced significant elevation in thiobarbituric acid reactive substances (TBARS), indicating lipid peroxidation, and significantly inhibited the activity of superoxide dismutase (SOD) in heart and liver tissues. In contrast, a single injection of ADR did not affect the cardiac or hepatic glutathione (GSH) content and cardiac catalase (CAT) activity but elevated hepatic CAT. Pretreatment with MPG, (2.5 mg/kg) intragastrically, significantly reduced TBARS concentration in both heart and liver and ameliorated the inhibition of cardiac and hepatic SOD activity. In addition, MPG significantly decreased the serum level of GOT, GPT, CK-MB, and LDH of ADR treated rats. These results suggest that MPG exhibited antioxidative potentials that may protect heart and liver against ADR-induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the high redox potential of sulfhydryl groups that limit the activity of free radicals generated by ADR.     

Attenuation of the acute adriamycin-induced cardiac and hepatic oxidative toxicity by N-(2-mercaptopropionyl) glycine in rats

The protective effect of the synthetic aminothiol, N-(2-mercaptopropionyl) glycine (MPG) on adriamycin (ADR) induced acute cardiac and hepatic oxidative toxicity was evaluated in rats. ADR toxicity, induced by a single intraperitoneal injection (15 mg/kg), was indicated by an elevation in the level of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase isoenzyme (CK-MB), and lactic dehydrogenase (LDH). ADR produced significant elevation in thiobarbituric acid reactive substances (TBARS), indicating lipid peroxidation, and significantly inhibited the activity of superoxide dismutase (SOD) in heart and liver tissues. In contrast, a single injection of ADR did not affect the cardiac or hepatic glutathione (GSH) content and cardiac catalase (CAT) activity but elevated hepatic CAT. Pretreatment with MPG, (2.5 mg/kg) intragastrically, significantly reduced TBARS concentration in both heart and liver and ameliorated the inhibition of cardiac and hepatic SOD activity. In addition, MPG significantly decreased the serum level of GOT, GPT, CK-MB, and LDH of ADR treated rats. These results suggest that MPG exhibited antioxidative potentials that may protect heart and liver against ADR-induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the high redox potential of sulfhydryl groups that limit the activity of free radicals generated by ADR.     

Effect of prolonged administration of insecticide (Cyhalothrin/Karate) on the blood and liver of rabbits.

A sublethal dose of Karate administered to rabbits produced a significant increase in the total erythrocyte count and packed cell volume after 15 days of administration, though no significant change was observed after 30 days. The transaminases (glutamate oxaloacetate transaminase, GOT; glutamate pyruvate transaminase, GPT) also increased after 15 days of treatment. The GPT activity increased 119% and 60% after 15 and 30 days, respectively. From amongst metabolites, glucose content increased 17% and 185%, while cholesterol decreased 40% and 66%, and bilirubin 84% and 61%, after 15 and 30 days, respectively. The hepatic AkP activity decreased 30%, while the GPT activity increased 44%. Other enzymes such as AcP, GOT and LDH remained unaffected. The concentration of other metabolites, except for FAA which increased 35%, remained unaffected. Histological changes were marked by atrophied hepatic cells and hypertrophied nuclei and nucleoli. A trend towards necrosis of hepatic cells was also observed. All these results indicate that Karate is moderately toxic to mammals.     

Effect of altered hormonal states on transaminase enzymes in the genital ograns of immature female rhesus monkeys

The effect of ovariectomy and hormone replacement therapy on the activity of glutamate oxalacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) in the oviduct, uterus, cervix and vagina of immature female rhesus monkeys (Macaca mulatta ) was studied. In intact animals, GOT activity was high in the oviduct, whereas GPT was high in the vagina. Ovariectomy suppressed the activity of both the enzymes in varying degrees. Estradiol dipropionate stimulated GOT in the oviduct and uterus, whereas progesterone increased this enzyme in the uterus. Sequential treatment of two hormones inhibited the enzymes in all the tissues; GPT was, however, stimulated in the fundus region of the uterus. The study demonstrated the presence of transaminase enzymes in the genital tissues of rhesus monkey and their differential response to sex steroids.     

注射用丹酚酸A防治肝纤维化的实验研究

目的：探讨注射用丹酚酸A抗肝纤维化的作用,为丹酚酸A的临床应用提供理论依据。方法采用CCl4体外诱导肝细胞损伤,观察丹酚酸A对肝细胞活性及其细胞培养上清液ALT、AST、LDH水平和细胞裂解液中SOD活性和MDA含量的变化;另采用皮下注射CCl4诱导大鼠肝纤维化模型,观察丹酚酸A对肝纤维化大鼠血清LN、HA、SOD和MDA含量的影响以及肝脏组织病理改变情况。结果与模型对照组比,丹酚酸A高、低剂量组和Vit E组的细胞存活率显著提高（P ＜0.01）,丹酚酸A高剂量组ALT、AST和LDH活性显著降低（P ＜0.01）,丹酚酸A高剂量组和Vit E组SOD活性明显升高（P ＜0.05）,MDA含量显著降低（P ＜0.05）;体内试验发现,与模型对照组比,丹酚酸A高剂量组纤维化大鼠的血清LN和HA水平显著降低（P ＜0.05）,高、低剂量组SOD活性显著升高（P ＜0.05, P ＜0.01）,MDA含量显著降低（P ＜0.01, P ＜0.05）,并能改善肝脏病理形态。结论注射用丹酚酸A可通过抗脂质过氧化作用,起到保护肝细胞,减轻肝纤维化的作用。     

肝细胞生长因子对四氯化碳损伤原代培养大鼠肝细胞的保护…

本工作采用无血清原供培养大鼠肝细胞法,观察了重组人肝细胞生长因子对四氯化碳致大鼠肝细胞损伤的保护作用。结果表明,ｒ－ｈＨＧＦ对ＣＣｌ４染毒肝细胞有明显的保护作用。ｒ－ｈＨＧＦ保护组较ＣＣｌ４染毒组细胞存活率显著升高,细胞内丙氨酸转氨酶,钾离子漏出明显降低。     

苯酚对多刺裸腹溞糖及蛋白质代谢酶的影响

采用急性毒性方法,研究了苯酚对多刺裸腹溞(Moina macrocopa)糖及蛋白质代谢的影响。实验设对照组和5个苯酚处理组,苯酚浓度分别为0.25、0.75、1.25、1.75、2.25 mg/L。分别在苯酚处理24 h和48 h后用分光光度法测定丙酮酸激酶(PK)、乳酸脱氢酶(LDH)、琥珀酸脱氢酶(SDH)、谷草转氨酶(GOT)和谷丙转氨酶(GPT)的活力。结果显示,随着苯酚浓度的增加和处理时间的延长,LDH活力呈现升高趋势,PK和SDH活力与对照组相比没有显著性差异。GOT活力在处理24 h后先升后降,处理48 h后活力降低;GPT活力在处理24 h、48 h后活力均升高。结论是:苯酚中毒需要高水平的代谢能量,导致裸腹溞代谢发生重大改变,诱导能量代谢一定程度上由碳水化合物分解代谢向蛋白分解代谢转变。