Aqueous extract of Anoectochilus formosanus attenuate hepatic fibrosis induced by carbon tetrachloride in rats.

The aim of this study was to investigate the effects of aqueous extract of Anoectochilus formosanus (AFE) on liver fibrogenesis in carbon tetrachloride (CCl4)-induced cirrhosis. Fibrosis was induced in rats by oral administration of CCl4 (20%, 0.5 ml/rat, p.o.) twice a week for 8 weeks. AFE (0.5 and 2.0 g/kg, p.o., daily for 8 weeks) was administered to rats simultaneously. AFE showed reducing actions on the elevated levels of GOT and GPT caused by CCl4. Liver fibrosis in rats induced by CCl4 led to the drop of serum albumin concentration; the AFE increased the albumin concentration. The CCl4-induced liver fibrosis markedly caused liver atrophy and splenomegalia, while AFE increased the liver weight, and decreased the spleen weight. The CCl4-induced liver fibrosis decreased the protein content, and increased collagen contents in rat's liver. AFE significantly increased the contents of protein and reduced the amount of collagen in the liver. In CCl4-treated rats, glutathione concentrations of liver were not affected. AFE significantly increased liver glutathione concentrations. All these results clearly demonstrate that AFE can reduce the liver fibrogensis in rats induced by CCl4.     

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.     

The role of thromboxane A2 [TxA2] in liver injury in mice

The role of thromboxane A2 (TxA2) in CCl4-induced liver disease was investigated in mice. Significant elevation of TxB2 in the liver was observed 6 hours after the injection of CCl4. Administration of OKY-046, a selective TxA2 synthetase inhibitor (10 and 50 mg/kg) and ONO-3708, a TxA2 receptor antagonist, (0.5, 1 and 2 mg/Kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes of the liver. In addition, OKY-046 inhibited the elevation of TxB2 in the liver. When U-46619, a stable TxA2 mimetic was injected i.v. into the mice, clear elevation of serum GOT and GPT levels and histopathological score of the liver were observed. These results suggest that TxA2 play a role for the onset of CCl4-induced liver injury in mice.     

Protective effect of chromium(III) on acute lethal toxicity of carbon tetrachloride in rats and mice.

Trivalent chromium (Cr(III)) preadministered intraperitoneally (5 mg Cr/kg body weight) to rats and mice protected these animals from acute lethal toxicity of carbon tetrachloride (CCl4). Some other metals, Cr(VI), Cu(II), and Zn(II), had no effect on CCl4 lethal toxicity. DL-alpha-tocopherol, one of the antioxidative agents, showed similar protective effects to Cr(III). Activities of serum GOT and GPT in mice were increased sharply by the administration of CCl4, but these elevations were depressed by Cr(III) preadministration. Serum glucose levels of mice increased transiently after CCl4 administration and then in the control group fell to hypoglycemic levels after 6 hr, whereas the Cr(III)-pretreated group kept to homeostatic levels. Lipid peroxidation of microsomes in mice 24 hr after Cr(III) administration was lower than that of the control. These results suggest that Cr(III) preadministered to mice might act as a radical scavenger to CCl4 to form trichloromethyl radicals which are a major initial product of CCl4 in liver cells.     

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.     

Hepatoprotective and antioxidant effects of Hibiscus sabdariffa extract against carbon tetrachloride-induced hepatocyte damage in Cyprinus carpio

The present study aims to evaluate the hepatoprotective and antioxidant effects of Hibiscus sabdariffa extract on the carbon tetrachloride (CCl(4))-induced hepatocyte damage in fish and provide evidence as to whether it can be potentially used as a medicine for liver diseases in aquaculture. H. sabdariffa extract (100, 200, and 400?μg/mL) was added to the carp primary hepatocyte culture before (pre-treatment), after (post-treatment), and both before and after (pre- and post-treatment) the incubation of the hepatocytes with CCl(4). CCl(4) at 8?mM in the culture medium produced significantly elevated levels of lactate dehydrogenase (LDH), glutamate oxalate transaminase (GOT), glutamate pyruvate transaminase (GPT), and malondialdehyde (MDA) and significantly reduced levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Pre-treatment and pre- and post-treatment of the hepatocytes with H. sabdariffa extract significantly reduced the elevated levels of LDH, GOT, GPT, and MDA and increased the reduced activities of SOD and GSH-Px in a dose-dependent manner; post-treatment did not show any protective effect. The results suggest that H. sabdariffa extract can be potentially used for preventing rather than curing liver diseases in fish.     

Hepatic and renal changes in albino rats caused by the administration of chromium (VI) in drinking water

The effects of sodium chromate administered in drinking water on liver and kidney of albino rats have been studied, through investigation of histological alterations and monitoring changes on serum urea levels and transaminases (GOT and GPT). Measurements have been done after 4, 8 and 12 weeks of treatment. The liquid intake of treated animals decreases with time. The amount of water drunk by treated rats is 1/2 of that drink by controls after 12 weeks. The histological alterations in liver and kidney are similar to those described elsewhere. Serum urea level is always higher in treated animals than in controls. GOT levels are similar in both treated and control rats, although always higher in the treated ones. GPT levels increase significantly after 12 weeks of treatment.     

非酒精性脂肪肝大鼠PPARα基因表达及脂代谢和胰岛素水平的变化

目的观察非酒精性脂肪肝（NAFLD）大鼠肝组织中PPARα基因的表达,并用PPARct激动剂进行干预,探讨其与胰岛素抵抗、脂代谢紊乱的关系。方法大鼠随机分为①正常对照组、②高脂模型组、③PPARα激动剂干预组,利用高脂饮食建立大鼠非酒精性脂肪肝模型。12周后,检测大鼠血脂、肝功能、血糖、胰岛素水平及胰岛素抵抗指数;RT-PCR法分析PPARα基因的表达;观察肝脏的形态学改变。结果PPARa激动剂可降低NAFLD大鼠转氨酶、血脂水平及胰岛素抵抗指数,可促进NAFLD大鼠中PPARa基因的表达;肝脏形态学明显改善。结论PPARα激动剂能改善NAFLD大鼠脂质代谢紊乱,有明显的保肝降酶作用,具有适度的胰岛素增敏作用。PPARα及其配体在NAFLD发病机制及治疗中的进一步深入研究,将为临床防治NAFLD提供新的思路。     

Hepatoprotective effects of Solanum nigrum Linn extract against CCl(4)-induced oxidative damage in rats

Solanum nigrum L. (SN) is an herbal plant that has been used as hepatoprotective and anti-inflammation agent in Chinese medicine. In this study, the protective effects of water extract of SN (SNE) against liver damage were evaluated in carbon tetrachloride (CCl4)-induced chronic hepatotoxicity in rats. Sprague-Dawley (SD) rats were orally fed with SNE (0.2, 0.5, and 1.0 g kg(-1) bw) along with administration of CCl4 (20% CCl4/corn oil; 0.5 mL kg(-1) bw) for 6 weeks. The results showed that the treatment of SNE significantly lowered the CCl4-induced serum levels of hepatic enzyme markers (GOT, GPT, ALP, and total bilirubin), superoxide and hydroxyl radical. The hepatic content of GSH, and activities and expressions of SOD, GST Al, and GST Mu that were reduced by CCl4 were brought back to control levels by the supplement of SNE. Liver histopathology showed that SNE reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, hepatic necrosis, and fibrous connective tissue proliferation induced by CCl4 in rats. Therefore, the results of this study suggest that SNE could protect liver against the CCl4-induced oxidative damage in rats, and this hepatoprotective effect might be contributed to its modulation on detoxification enzymes and its antioxidant and free radical scavenger effects.     

Correlations between common tests for assessment of liver damage: indices of the hepatoprotective activity of promethazine in carbon tetrachloride hepatotoxicity

The effects of promethazine (PM) on different aspects of the hepatotoxic action of CCl4 in the rat were investigated with the objective of finding rapid and reliable indicators of hepatoprotective effects. The study was based on definitive histological assessment of liver damage caused by CCl4 in the presence and absence of PM: PM (78 mumol kg-1, i.p.) protected against CCl4-induced hepatic necrosis 24 h after a low dose of CCl4 (1.3 mmol kg-1) but not against a higher dose (13.0 mmol kg-1). The large increases in plasma activities of GOT, GPT and LDH produced by dosing with CCl4 were partially inhibited by the administration of PM. PM and CCl4 caused a synergistic and long-lasting decrease in body temperature (2-3 degrees C for 8-10 h). Modifying the toxicity with PM, together with a low dose of CCl4, helped to minimize secondary effects of CCl4, to clarify the sequence of toxic events, and to assess the sensitivity of some standard tests of hepatotoxicity. Simultaneous measurement of over 20 commonly used biochemical screening tests in individual animals 3 or 6 h after treatment permitted direct correlation of a wide variety of concentrations, activities and effects. For example, liver CHCl3 concentrations (as a measure of CCl4 metabolism) correlate strongly with increases in diene conjugation of microsomal lipids (as a measure of CCl4-induced lipid peroxidation); malonaldehyde production appears to be less sensitive as a measure of lipid peroxidation in vivo than diene conjugation. The changes induced in each parameter and the correlations between them are discussed with reference to the overall nature of the hepatotoxic reaction and its modification by PM.     

Clinical blood chemistry values in normal Wistar-Imamichi rats using the RaBA-System (author's transl)]

In order to establish the normal baseline of blood values in rats using the RaBA-System, the following eight parameters were analyzed in 8-22-week-old Wistar-Imamichi rats of both sexes: hemoglobin, total protein, glucose, BUN, total cholesterol, GOT, GPT, and alkaline phosphatase. With the exception of glucose, all these parameters were significantly different depending upon ages. Significant sex differences were observed in the values of hemoglobin, total cholesterol, GOT, and alkaline phosphatase.     

槟榔碱对2型糖尿病大鼠肝脏胰岛素抵抗的作用

目的：探讨槟榔碱对2型糖尿病大鼠肝脏胰岛素抵抗的影响及其机制。方法：采用高果糖饲料饲养Wistar大鼠12周制备2型糖尿病大鼠模型,实验动物随机分为5组（n=8）：对照组、模型组、模型＋不同浓度的槟榔碱（0,0．5,1,5mg／kg）组。4周后通过检测血糖、血脂、胰岛素、RT-PCR检测肝脏组成型雄甾烷受体（CAR）、孕甾烷x受体（PXR）、糖代谢相关基因：葡萄糖-6-磷酸酶（G6Pase）、磷酸烯醇式丙酮酸羧激酶（PEPCK）和炎症相关因子：白细胞介素-6（IL-6）、肿瘤坏死因子α（TNF-α）mRNA表达,Western blot检测大鼠肝内p-AKT和葡萄糖转运体4（GLUT4）蛋白表达。结果：1,5mg／kg槟榔碱显著降低糖尿病大鼠体重、空腹血糖、空腹胰岛素、血脂和糖代谢相关基因及炎症相关因子mRNA水平,提高CAR、PXR mRNA水平及p-AKT、GLUT4蛋白水平。结论：槟榔碱可能通过提高CAR和PXR的表达,导致肝脏糖代谢关键酶PEPCK、G6Pase基因表达或者炎性因子肿瘤坏死因子-α（TNF-α）、白介素-6（n-6）表达降低,改善2型糖尿病大鼠肝脏胰岛素抵抗。     

Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats

The effects of hypothalamic stimulation on experimental liver injury induced by carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN) were studied in rats, by measuring plasma alanine aminotransferase (ALT) activity as an index of acute liver injury. Electrical stimulation of the ventromedial hypothalamus (VMH) in CCl4-treated rats caused a marked increase in plasma ALT activity, accompanied by a significant decrease in ALT activity in the liver, although CCl4 treatment alone had no significant effect on plasma ALT activity. A similar effect of VMH stimulation on plasma ALT activity was observed in rats treated with DMN, another hepatotoxic chemical. No such exaggerated effect of VMH stimulation on plasma ALT activity was observed after stimulation of the lateral hypothalamic area (LH). Surgical sympathetic denervation of the liver greatly suppressed the increase in plasma ALT activity after CCl4 injection and VMH stimulation. Measurement of regional blood flow indicated that VMH stimulation did not produce a significant change in blood flow to the liver. These results suggest that the VMH is involved in the progress of chemically-induced liver injury through activation of the sympathetic nerve (hepatic nerves), possibly by affecting liver metabolism more than the blood flow change to the liver.     

CCl4致小鼠肝损伤中几种免疫介质含量变化的研究

本文通过研究CCl4致小鼠肝损伤组织匀浆和血浆一些免疫介质含量的变化以探讨这些免疫介质在CCl4诱发肝损伤过程中作用机制。分别选用30只健康成年小鼠,雌雄各半,随机分成对照组和CCl4负荷组,每组15只。通过腹腔注射CCl4诱发肝损伤后,分别在第2、4、6周检测肝组织匀浆cAMP、cGMP和MDA及血浆IL-2、TNF-α水平的变化。结果显示,在整个实验期内,CCl4组肝组织匀浆cAMP水平均低于或明显低于对照组;cGMP在实验第2周后,高于或显著高于对照组;cAMP／cGMP比值呈现下降趋势,并低于或明显低于对照组;MDA含量明显高于对照组。在整个实验期内,CCl4组血浆IL-2水平下降或显著下降;TNF-α水平则均高于或显著高于对照组。结果提示,CCl4负荷诱发免疫介质cAMP、cGMP、TNF-α和IL-2发生剧烈变化,在介导肝损伤过程中可能起重要作用。     

非酒精性脂肪肝大鼠脂质代谢及病理变化的动态观察

目的通过高脂饮食建立NAFLD大鼠模型,连续监测4～16周模型动物肝功能、脂质代谢、胰岛素抵抗及肝细胞凋亡在NAFLD进展过程中的变化情况及相互关系,为该模型在脂肪肝发病机制、脂肪肝治疗药物评价等方面的应用提供参考依据。方法 SD大鼠50只,除正常对照组外,其余动物饲喂高脂饲料,分别检测4,8,12,16周大鼠血清GLU、CHO、TG、HDL、LDL、GPT、GOT及胰岛素水平,肝脏组织切片进行病理学及细胞凋亡观察,进一步分析大鼠肝功能、脂质代谢、胰岛素抵抗及肝细胞凋亡对肝组织病理改变的影响。结果模型组大鼠4周后就出现肝功能损伤,脂质代谢紊乱、胰岛素抵抗,肝细胞凋亡8 W后明显增加,肝细胞脂变及炎症为肝组织病理变化的主要特征,且造模时间越长,病变程度越严重。结论经过高脂饲料的喂养,SD大鼠在4～16周内可形成病变程度逐步加重的NAFLD模型,肝功能损伤,脂质代谢紊乱及肝细胞凋亡是引起非酒精性脂肪肝中脂肪变性和炎症的重要因素,该模型可应用于脂肪肝治疗药物评价等方面。     

Blood and liver enzymes in rainbow trout (Salmo gairdneri Rich.) with emphasis on their diagnostic use: Study of CCl4 toxicity and a case of Aeromonas infection

The effect of one intraperitoneal injection of 1.33 ml of CCl₄ per kg of fish was studied. Two experimental series were performed and studied for 10 days (with diluent) and 24 h (pure CCl₄) periods. LDH, GOT, GPT, GR, GDH, CPK, G-6-Pase, and AlkPase were studied. The activity of all enzymes in blood increased: LDH (four times the control), GOT (two times), GPT (three times); they reached a maximal activity 12 h after injection of diluted CCl₄. The levels of some enzymes were also examined in the liver. With pure CCl₄, maximal enzyme activity in blood occurred earlier (6 h). A 6 to 10 times increase was observed for GOT, GPT, LDH, GR, and GDH. Histopathological observations were correlated with these enzymes studies.
An Aeromonas disease characterized by the destruction of the dermis, the exposure of the muscle, and by the presence of numerous petechiae in the liver enabled us to examine the relationships between naturally induced tissue damage and enzyme levels in blood. The levels of seven blood enzymes were determined and the most significant modifications were observed for LDH and CPK. which increased their concentration from 3 to 7 times respectively. A pyruvate saturation test demonstrated that LDH was probably from liver as it was observed after CCl₄ poisoning. The contribution of such biochemical studies in fish research is evaluated.     

The effect of S-adenosyl-L-methionine (SAM) on membrane permeability in the perfused rat liver

S-adenosilmethionine is present in most human tissues and is an important factor for transmethylation, transulphuration and aminopropylation reactions. The compound improves the biological, morphological and histochemical aspects of rat liver following CCl4 intossication. At the same time has been successfully used during chronic liver disease in man. With the aim to better clarify the action mechanism of SAMe some aspects concerning its effects on cell permeability in rat liver, by using the perfusion technique, have been investigated. In particular the capacity of this compound to prevent the enzymatic loss (GPT and GOT) during liver perfusion has been studied. 30 perfusions without SAMe, as control, and 6 by infusing 2 mg of compound during the perfusion time have been accomplished. Varing the perfusion time from 0 to 120 min it has been observed that at any time the presence of the SAMe reduced by about 50% the loss of GOT. Similarly the activity of GPT ranging from 2 to 6 mU/ml indicate that no appreciable enzyme output occurs in presence of SAMe.     

Destruction of hepatic mixed-function oxygenase parameters by CCl4 in rats following acute treatment with chlordecone, Mirex, and phenobarbital

Previous work has established the marked potentiation of CCl4 hepatoxicity by prior exposure to chlordecone (CD). This study was conducted to determine if prior exposure to CD results in enhancement of CCl4-induced destruction of the hepatic microsomal mixed-function oxygenase (MFO) system. Male Sprague-Dawley rats received a single oral dose of CD (10 mg/kg) or corn oil vehicle alone (1 ml/kg) 24 hr prior to a single ip injection of CCl4 (0-100 microliter/kg). Mirex (M; 10 mg/kg) and phenobarbital (PB; 80 mg/kg/day for two days) were used as negative and positive controls respectively for the potentiation of CCl4 hepatotoxicity. Hepatotoxicity was evaluated 24 hrs after CCl4 administration by elevations of three serum enzymes (GPT, GOT, and ICD). The key hepatic microsomal MFO parameters measured were microsomal protein, cytochrome P-450 content, glucose-6-phosphatase (G-6-Pase), and aminopyrine demethylase (APD). As previously demonstrated using a subchronic dietary pretreatment protocol, CD potentiated CCl4 hepatotoxicity over a range of CCl4 doses to a greater extent than PB or M, as judged by elevations in serum enzymes. PB caused the greatest increase in total P-450 content and the greatest increase in CCl4-mediated destruction of microsomal protein and APD activity. M caused the least destruction of total hepatic cytochrome P-450, despite the same level of cytochrome P-450 as in the PB group. CD treatment caused the greatest decrease in G-6-Pase activity in comparison to PB or M pretreatments and a similar degree of P-450 destruction as observed with the PB group. These findings suggest that in general, CCl4-induced destruction of hepatic MFO parameters measured in this study is disproportional to the known degree of potentiated hepatotoxicity by the pretreatments and does not accurately reflect the potentiation of CCl4 hepatotoxicity by CD.     

Influence of Carbon Tetrachloride on Inducible Liver Enzymes and Response to Endotoxin in Mice

Injection of mice with a sublethal dose of endotoxin 2 hr after administration of 0.1 ml of carbon tetrachloride (CCl(4)) killed 75% of the animals. CCl(4) alone killed no controls. Significant protection against this effect was afforded by 5 mg of cortisone and by 5 mg of nicotinamide adenine dinucleotide (NAD). With a larger dose of endotoxin, cortisone did not give protection. Liver tryptophan pyrrolase activity was lowered 2 hr after CCl(4) injection and reached a minimum after 17 hr. Induction of tryptophan pyrrolase by cortisone, followed by administration of CCl(4), resulted in rapid loss of activity. A significant induction of tyrosine-alpha-ketoglutarate transaminase was observed in CCl(4)-treated mice. The induction of this enzyme by cortisone was somewhat impaired when CCl(4) was administered concurrently with the hormone. CCl(4) did not lower tryptophan pyrrolase in endotoxin-tolerant mice after 4 hr, but at 17 hr the activity was decreased as much as in control mice. Oxidized pyridine nucleotides were decreased 17 hr after administration of CCl(4). This loss was prevented by administration of NAD (5 mg) or by cortisone (5 mg). Carbon clearance from blood was reduced after treatment with CCl(4). These results indicate a degree of similarity between the metabolic effects of endotoxin and CCl(4) in that both depress tryptophan pyrrolase and prevent its induction by cortisone, and both induce tyrosine transaminase in intact mice. Both substances appear to exert these effects through some type of mediated reaction.     

The roles played by crucial free radicals like lipid free radicals, nitric oxide, and enzymes NOS and NADPH in CCl(4)-induced acute liver injury of mice

Mice were administered a single dose of carbon tetrachloride (CCl(4)) to induce acute liver injury. We found that lactate dehydrogenase (LDH) and glutamic pyruvic transaminase (GPT) levels in serum, as well as the level of thiobarbituric acid reaction substances (TBARS) in liver homogenate increased significantly in a manner both dose dependent and time dependent after CCl(4) administration. Such results suggest that the liver is susceptible to CCl(4) treatment and that lipid peroxidation is associated with CCl(4)-induced liver injury. The spin-trapping electron paramagnetic resonance (EPR) method was used to detect nitric oxide (NO) level in liver. The chemiluminescence method was also employed to measure the NO(2)(-)/NO(3)(-) concentration in serum. The NO levels in liver tissues and NO(2)(-)/NO(3)(-) concentration in serum were found to decrease significantly both in a dose-dependent manner and in time course after CCl(4) treatment. The nitric oxide synthase (NOS) II activity in the liver, in contrast, was found to increase significantly. Our study suggests that not only should the expression of NOS be analyzed but NO organ and blood concentration must be measured in the study of diseases involving nitric oxide. L-arginine treatment had no significant effect on the liver function of CCl(4)-treated mice. It was found that NO donor sodium nitroprusside (SNP; 50 or 100 microg/kg) treatment resulted in decreases of LDH, GPT, and TBARS levels, leading to a protective effect on CCl(4)-treated mice. On the other hand, N(G)-nitro-L-arginine methyl ester (L-NAME, 100 or 300 mg/kg) treatment caused more severe liver damage. Moreover, we have found in an in vitro EPR study that SNP could scavenge lipid peroxyl radical LOO&z.rad;. The above results together suggest that NO may protect CCl(4)-induced liver injury through scavenging lipid radical, inhibiting the lipid peroxidation chain reaction. On the basis of our analysis, we put forth two explanations for the stated discrepancy between NOS II and NO production: (i) NO was used up gradually in terminating lipid peroxidation and (ii) NADPH was depleted (on the basis of correlation evidence only).