Elevated lipid peroxidation in rats induced by dietary lipids and N-nitrosodimethylamine and its inhibition by indomethacin monitored via ethane exhalation

The effect of dietary lipids alone or in combination with an administered carcinogen, N-nitrosodimethylamine (NDMA), on whole body lipid peroxidation was studied in rats in vivo. Groups of rats were fed diets containing 2%, 12.5%, or 25% of either saturated or polyunsaturated fat. Lipid peroxidation in individual animals was determined by measuring the concentration of ethane in exhaled air. Increased ethane exhalation was found in rats when the amount of dietary fat was increased from 2% to 12.5%, but animals receiving 12.5% or 25% fat in the diet exhaled ethane at similar rates. Rats consuming polyunsaturated fat exhaled more ethane than those eating saturated fat. In all groups, NDMA administration drastically increased ethane exhalation. Indomethacin completely blocked the increase in ethane exhalation caused by dietary lipids.     

Hepatic toxicity of nickel chloride in rats

Enhanced lipid peroxidation was observed in livers of rats killed 24 hr after sc injection of nickel chloride (NiCl2) (750 mumol per kg), as evidenced by 13-fold increase of conjugated dienes in microsomal lipids and 4-fold increase of thiobarbituric acid (TBA) chromogens in hepatic cytosol. Histologic examination of livers from rats killed one to three days after NiCl2 injection (500 mumol per kg) showed microvesicular fatty metamorphosis, mild hydropic degeneration, and foci of inflammation. Microvesicular steatosis of hepatocytes was confirmed by electron microscopy. Dose-related increases of serum aspartate aminotransferase (ALT) activity (up to 7-fold vs controls) and alanine aminotransferase (ALT) activity (up to 3-fold vs controls) were observed 24 hr after injection of NiCl2 (125 to 750 mumol per kg); diminished serum alkaline phosphatase activity (up to 72 percent reduction vs controls) was seen at NiCl2 dosages from 375 to 750 mumol per kg. Diethyldithiocarbamate did not influence the effects of NiCl2 on TBA-chromogens in liver homogenates or on serum AST and ALT activities but acted synergistically with NiCl2 to diminish serum alkaline phosphatase activity and to increase serum bilirubin concentration. This study demonstrates that parenteral administration of NiCl2 to rats produces acute hepatic toxicity, with enhanced lipid peroxidation, microvesicular steatosis, and increased serum AST and ALT activities.     

Increased lipid peroxidation in tissues of nickel chloride-treated rats

Parenteral administration of nickel chloride (NiCl2) to rats enhanced lipid peroxidation in liver, kidney, and lung (but not in brain, heart, spleen, or testis), as measured by the thiobarbituric acid reaction for malondialdehyde (MDA) and related chromogens in fresh tissue homogenates. After sc injection of NiCl2 (0.75 mmol per kg body wt), MDA concentrations in liver and kidney became significantly increased by nine h and reached peak values at 48 h. For example, in nine rats killed 48 h after the NiCl2 injection, hepatic MDA concentrations averaged 2.5 +/- 1.0 mumol per g dry wt (P less than 0.001 versus 0.5 +/- 0.3 mumol per g in 30 controls). Dose-effect relationships for lipid peroxidation in liver and kidney were observed with NiCl2 dosages ranging from 0.12 to 0.75 mmol per kg, sc. Intrarenal administration of a carcinogenic nickel compound, nickel subsulfide (Ni3S2, 0.36 mmol per kg body wt), did not affect MDA concentrations in the injected kidneys of rats killed one to 20 days post-injection. The results of this study implicate lipid peroxidation as a molecular mechanism for cell injury in acute NiCl2 poisoning, but they do not furnish any evidence that lipid peroxidation is involved in the initiation of nickel carcinogenesis.     

Effects of nickel chloride and diethyldithiocarbamate on metallothionein in rat liver and kidney

Effects of NiCl2 and sodium diethyldithiocarbamate (DDC) upon metallothionein (MT) concentrations were studied in liver and kidney of male Fischer rats. After injection of NiCl2 (0.75 mmol per kg, sc), hepatic MT concentration increased 2.6-fold at 6.5 hr and 8.2-fold at 17 hr; renal MT concentration increased 1.4-fold at 6.5 hr and 2.3-fold at 17 hr. Dose-related increases of MT concentrations were observed in liver and kidney of rats killed 17 hr after injection of NiCl2 (0.25 to 0.75 mmol per kg, sc). Repeated administration of NiCl2 (0.1 mmol per kg, ip) on four successive days, with sacrifice three days after the last treatment, increased MT concentrations 1.4-fold in liver and kidney, whereas CdCl2-treatment at the same dosage schedule increased MT concentration 16-fold in liver and 3.3-fold in kidney. NiCl2-Induction of MT in liver and kidney was not prevented by actinomycin D (1 mg per kg, ip), but was inhibited by cycloheximide (2 mg per kg, ip). Sodium diethyldithiocarbamate given alone (1.33 mmol per kg, im) 17 hr before death, increased MT concentration 7.6-fold in liver but did not affect MT concentration in kidney; administration of DDC prior to injection of NiCl2 did not inhibit NiCl2-induction of MT.     

Oleuropein attenuates cognitive dysfunction and oxidative stress induced by some anesthetic drugs in the hippocampal area of rats

The present study was designed to evaluate the antioxidant effects of oleuropein against oxidative stress in the hippocampal area of rats. We used seven experimental groups as follows: Control, Propofol, Propofol-Ketamine (Pro.-Ket.), Xylazine-Ketamine (Xyl.-Ket.), and three oleuropein-pretreated groups (Ole.-Pro., Ole.-Pro.-Ket. and Ole.-Xyl.-Ket.). The oleuropein-pretreated groups received oleuropein (15 mg/kg body weight as orally) for 10 consecutive days. Propofol 100 mg/kg, xylazine 3 mg/kg, and ketamine 75 mg/kg once as ip was used on the 11th day of treatment. Spatial memory impairment and antioxidant status of hippocampus were measured via Morris water maze, lipid peroxidation marker, and antioxidant enzyme activities. Spatial memory impairment and lipid peroxidation significantly increased in Xyl.-Ket.-treated rats in comparison to the control, propofol, Ole.-Pro. and Ole.-Pro.-Ket. groups. Oleuropein pretreatment significantly reversed spatial memory impairment and lipid peroxidation in the Ole.-Xyl.-Ket. group as compared to the Xyl.-Ket.-treated rats. There was no significant difference between the control and the propofol group in lipid peroxidation and spatial memory status. Superoxide dismutase and catalase activities both significantly decreased in Xyl.-Ket.-treated rats when compared to the control, propofol, Ole.-Pro., Ole.-Pro.-Ket., and Ole.-Xyl.-Ket. groups. In contrast, glutathione peroxidase activity in Xyl.-Ket.-treated rats significantly increased as compared to the control, propofol, Pro.-Ket., Ole.-Pro., and Ole.-Pro.-Ket. groups. We concluded that xylazine in combination with ketamine is an oxidative anesthetic drug and oleuropein pretreatment attenuates cognitive dysfunction and oxidative stress induced by anesthesia in the hippocampal area of rats. We also confirmed the antioxidant properties of propofol as a promising antioxidant anesthetic agent.     

Age-associated oxidative damage in microsomal and plasma membrane lipids of rat hepatocytes

Phosphatidylcholine hydroperoxide (PC-OOH) and phosphatidylethanolamine hydroperoxide (PE-OOH) concentrations were determined in microsomes and plasma membranes prepared from 2- and 17-month-old male Sprague-Dawley rat hepatocytes, to verify the dissimilarity of age dependency of lipid peroxidation in organelle membranes. The hydroperoxides were directly measured by chemiluminescence detection–high-performance liquid chromatography (CL–HPLC), and 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylcholine (PLPC-OOH) and 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylethanolamine (PLPE-OOH) were enzymatically synthesized and utilized as standards for the calibration. Baseline concentrations of hydroperoxides (PC-OOH+PE-OOH) of the 17-month-old rats were 46 pmol per mg protein in microsomes (2.7 times higher than the 2-month-old rats) and 306 pmol per mg protein in plasma membranes (9.9 times higher than the 2-month-old rats). Both microsomal and plasma membrane lipids were severely peroxidized and converted to phospholipid hydroperoxides by NADPH-dependent lipid peroxidation in vitro, but the age-dependency was only observed in the plasma membranes. These results demonstrate that substantial oxidative damage to membrane phospholipids occurs with ageing both in microsomes and plasma membranes, but is more prevalent in plasma membranes in rat hepatocytes.     

Experimental acetaminophen-induced hepatic necrosis: biochemical and electron microscopic study of cysteamine protection.

In an attempt to elucidate the biochemical mechanism of acetaminophen-induced hepatic necrosis, the present study in hamsters was undertaken to evaluate the possible changes in lipid peroxidation and microsomal enzyme activities. The protective action of cysteamine was likewise assessed in the light of these biochemical variables and the fine structural features of the liver were seen by electron microscopy. One group of golden Syrian hamsters was administered a toxic dosage of acetaminophen (600 mg . per kg . intraperitoneally) while another group was treated with the same dosage of acetaminophen, followed 1 hour later by cysteamine (200 mg . per kg . intraperitoneally). The animals were sacrificed at 6, 12, 18, and 24 hours. Microsomal fractions were isolated for biochemical assays, and liver sections were prepared for electron microscopy. Results showed that significant enhancement of lipid peroxidation occurred in the untreated acetaminophen-poisoned group, as compared to the cysteamine-treated group. Glucose 6-phosphatase activity was markedly suppressed at 6, 12, and 18 hours after acetaminophen administration. Cysteamine treatment completely prevented the curtailment of NADPH-cytochrome c reductase and glucose 6-phosphatase activities in the protected group, and partially maintained aniline hydroxylase activity. Cytochrome P-450 level was unaffected in both the cysteamine-treated and the untreated groups at the respective time intervals. Electron microscopic examination showed progressive loss of the structural integrity of the endoplasmic reticulum, lipid infiltration, and vacuolation in the untreated acetaminophen-poisoned group. At 18 and 24 hours, sinusoidal congestion and myeloid figure formation were prominent. In the cysteamine-protected group, polysomes reassembled around the granular endoplasmic reticulum at 18 hours. It is postulated that lipid peroxide formed in vivo may facilitate the microsomal oxidation of acetaminophen to the toxic metabolite. NADPH-cytochrome c reductase is likely to be the locus within the NADPH-cytochrome P-450 electron transport chain susceptible to lipoperoxidation. The free radical-related lipoperoxidation may mediate the impairment of in vitro drug metabolism, as reflected by the depressed aniline hydroxylase activity. The abnormal phospholipid metabolism is manifested at the fine structural level by the myeloid body formation. The protective effects of cysteamine as seen in the attenuated lipid peroxidation and the consequent derangement of microsomal enzymes correlate well with the morphologic observations. Cysteamine protection is discussed in terms of its role as an inhibitor of the toxic metabolite formation.     

Determination of serum and organ malondialdehyde (MDA) concentration, a lipid peroxidation index, in Trypanosoma brucei-infected rats

Lipid peroxidation was assessed in the sera and various organs of rats experimentally infected with Trypanosoma brucei. Thirty-six adult albino rats divided into 2 groups of eighteen rats each were used in this study. In experiment one, a group of 18 rats were used and they were divided into three groups (A, B and C) of six rats each. Groups B and C rats were infected with 1.54 × 10⁵ trypanosomes per rat intraperitoneally, whereas group A served as uninfected control. The rats were bled on day 0 and subsequently at 7-day intervals for packed cell volume (PCV), sera peroxidation index and parasitaemia. Also, temperature and weight were taken on day 0 and subsequently at 7-day intervals. In experiment 2, 18 rats were also used. Six rats each were sacrificed on days 0, 14 and 28-postinfection. Five rats each were sacrificed on day 14 and day 28 post-infection (PI) from group B, and their organs were promptly collected and washed with normal saline and used for organ malondialdehyde (MDA) concentration. The infection led to an increase in lipid peroxidation index (MDA concentration) of sera samples. The serum MDA concentration of the infected rat group was significantly (p < 0.01) higher than in the uninfected group on days 21 and 28 PI. The increase was however reversed by diminazene aceturate (Berenil; Hoechst, Ireland) treatment at the dosage of 7 mg/kg body weight administered on day 14 PI. The organ lipid peroxidation index also increased significantly (p < 0.05) in the eye, lung and spleen. However, there was no significant (p > 0.05) increase of lipid peroxidation index in the kidney, heart, liver, testes and brain. Also, the mean weekly MDA concentration increased as the disease progressed, the mean weekly temperature and parasitaemia also increased, but the reverse was the case with the mean weekly body weight and PCV which declined as the disease progressed. The findings are indication that oxidative stress plays an important role in the pathology of trypanosomosis.     

Role of lipid peroxidation in enhancement of endotoxin hepatotoxicity.

The present study was undertaken in the rats to examine whether endotoxin hepatotoxicity is enhanced by increased lipid peroxidation. The rats were given 10 ml of water, corn oil or heated and oxygenated corn oil per kg body weight by stomach tube twice a day for 14 days, and then they were injected physiological saline solution or endotoxin (2 or 2.5 mg per kg body weight) into the tail vein. In the rats pretreated with water or corn oil, the activity of serum glutamic pyruvic transaminase was within the normal limit, and there was no conspicuous morphological change in the liver, except for accumulation of fine fat droplets in few liver cells. On the other hand, in the rats pretreated with heated and oxygenated corn oil, containing a large amount of lipid peroxides, accumulation of small fat droplets in the liver cells and a slight elevation of serum transaminase activity were induced. The challenge with endotoxin (2.5 mg per kg body weight) caused focal hepatocellular coagulative necrosis and a marked elevation of serum transaminase activity, irrespective of the sorts of pretreatment, and there was no significant difference in the biochemical change and the histopathological damage between the rats pretreated with water, corn oil and heated and oxygenated corn oil. These results suggest that increased lipid peroxidation does not contribute to the enhancement of endotoxin hepatotoxicity, although it is thought that carbon tetrachloride and ethanol enhance endotoxin hepatotoxicity by synergism between endotoxin and the chemicals through lipid peroxidation.     

Lipid peroxidation in rat brain is increased by simulated weightlessness and decreased by a soy-protein diet

This study tested whether or not simulated weightlessness by tail-suspension increases the levels of lipid peroxidation products in rat brain. The brain tissues of rats on a soybean diet were also assayed for lipid peroxidation products to evaluate the possible role of soy-protein as a dietary anti-oxidant. Male Sprague-Dawley rats were used. Group 1 rats were fed standard Purina rat chow ad libidum and served as controls. Group 2 rats were fed a soybean diet containing 37% soy-protein and were not tail-suspended. Group 3 rats were fed standard Purina rat chow ad libidum and were tail-suspended to induce simulated weightlessness. After 2 wk, all of the rats were killed. Each whole brain was segmented into frontal cortex, cerebellum, and brain stem. After a specific weight of each segment was excised, the residual tissues were combined and used as a whole brain sample. The samples were analyzed for lipid peroxidation products by a chromogenic assay that reacts with malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE). The mean concentrations of lipid peroxidation products (MDA plus 4-HNE) in whole brain, frontal cortex, cerebellum, and brain stem of the control rats ranged from 16 to 18 micromol/g; the corresponding means ranged from 10 to 13 micromol/g in rats fed the soybean diet, and from 22 to 26 micromol/g in the tail-suspended rats. Thus, the mean levels of lipid peroxidation products in brain tissues were decreased in the rats fed the soy diet and were increased in the rats that were tail-suspended to simulate weightlessness, when compared to those of rats fed a regular diet.     

The fatty acid composition of red cells deficient in glucose-6-phosphate dehydrogenase and their susceptibility to lipid peroxidation

Summary Oxidant damage to red cell membranes could play a part in the pathogenesis of acute and chronic haemolysis in glucose-6-phosphate dehydrogenase deficiency. Therefore, we studied the substrate for red cell membrane lipid peroxidation, i.e. the content of various polyunsaturated fatty acids in ghosts, and the susceptibility of red cells to lipid peroxidation in normal subjects and in subjects deficient in glucose-6-phosphate dehydrogenase. The fatty acid composition of red cell membranes and plasma was analysed by capillary column gas chromatography. The sensitivity of red cells to lipid peroxidation was evaluated after hydrogen-peroxide-induced oxidant stress. The degree of lipid peroxidation was monitored by measuring the release of pentane and ethane formed during the breakdown of n-6 and n-3 fatty acids. The red cell sensitivity to lipid peroxidation was found to be higher in subjects with glucose-6-phosphate dehydrogenase deficiency than in normal subjects. In the former, saturated fatty acids, in particular palmitic and stearic acid, were found to be decreased, whereas the proportion of arachidonic acid showed a clear increase. Fatty acid analysis of plasma did not reveal significant abnormalities in enzyme-deficient patients, which could explain the alteration of membrane fatty acids. Our results suggest that the increased content of substrate for lipid peroxidation, particularly arachidonic acid, in red cell membranes of subjects deficient in glucose-6-phosphate dehydrogenase, should be considered in an evaluation of an enhanced sensitivity to red cell lipid peroxidation.Abbreviations G-6-PD Glucose-6-phosphate dehydrogenase - GSH Reduced glutathione - GSSG oxidized glutathione - MCV Mean corpuscular volume - MDA Malondialdehyde - RBC Red blood cells - TBA Thiobarbituric acid     

Changes in the antioxidant system by TNP-470 in an in vivo model of hepatocarcinoma

The objective of this study was to determine in a rat model of hepatocarcinoma (HCC) the effects of the antiangiogenic agent TNP-470 on antioxidant enzymes, including catalase (CAT), superoxide dismutases (Mn-SOD and Cu,Zn-SOD), and glutathione peroxidase (GPx). Tumor was induced in male Wistar rats by diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene administration. Experiments were carried out 28 weeks after initiating the treatment. TNP-470 was administered at 30 mg/kg, 2 times per week from weeks 20 to 28. Carcinomatous tissue was growing outside dysplastic nodules in rats with HCC. HCC caused oxidative stress demonstrated by increased lipid peroxidation and oxidized/reduced glutathione ratio that was accompanied by a reduced activity of antioxidant enzymes Cu,Zn-SOD, GPx, and CAT. In contrast, Mn-SOD activity and expression were higher in hepatocarcinoma than in control groups. These effects were absent in animals receiving TNP-470. No significant differences between untreated and TNP-470-treated rats were observed in the expression of the Cu,Zn-SOD, glutathione peroxidise, and CAT. We conclude that TNP-470 inhibits expression and activity of Mn-SOD induced by experimental hepatocarcinogenesis. Oxidative stress reduction by TNP-470 accounts for yet another anti-cancer effect of this molecule.     

Evidence for lipid peroxidation in endotoxin-poisoned mice.

Ethane has been identified and quantitated in air exhaled by mice following intraperitoneal injection of 20, 40, or 200 mg of Escherichia coli O111:B4 lipopolysaccharide (LPS) per kg. Significant increases in ethane concentration occurred within 1 to 5 h after LPS administration. In addition, increased concentrations of malondialdehyde were found in crude homogenates of livers obtained from mice 16 h after administration of 20 mg of LPS per kg. These results suggest that lipid peroxidation may be an important mechanism responsible for LPS toxicity.     

Activation of lipid peroxidation in early degeneration of motor nerve fibers and the effect of antioxidants on its development]

It was established that early degeneration of motor fibers of the sciatic nerve of rats (24 and 48 hours after division) is marked by diminished activity of the antioxidant enzymes superoxide dismutase and glutathione reductase and activation of lipid peroxidation leading to increased accumulation of malonic dialdehyde. alpha-tocopherol acetate prevents activation of lipid peroxidation and partly suppresses the development of functional signs of degeneration (lowered amplitude of the M-response, slow restoration of the neuromuscular synapse, and decrement reaction to rhythm stimulation). OBQ2 oxidant (derivative of 4-anilino-5-methoxy-1,2-benzoquinone) had no effect on the rate of degeneration development, which is evidence of insufficiency of radical protection for realization of the anti-degeneration effect.     

A toxicokinetic study of nickel-induced immunosuppression in rats

The aim of the present study was to investigate dose- and time-dependent effects of NiCl2 on T-lymphocyte and macrophage-derived cytokine production in rats. Moreover we have determined the concentrations of nickel in the plasma that are required to elicit alterations in T-lymphocyte and macrophage function. NiCl2 suppressed T-lymphocyte proliferation and Th1 (IFN-gamma) and Th2 (IL-10) cytokine production in a dose- and time-dependent fashion. In addition, NiCl2 inhibited production of the pro-inflammatory cytokine TNF-alpha and increased production of the anti-inflammatory cytokine IL-10 from lipopolysaccharide (LPS) stimulated cultures. We have determined that the minimal plasma concentrations of nickel required to provoke immunosuppression are in the range 209-585 ng/mL. In the time-course study NiCl2 (3.3 mg/kg) provoked immunological changes that were maximal 1 h following administration, and some of these changes persisted for up to 24 h post administration. Overall these data clearly demonstrate that NiCl2 suppresses T-cell function and promotes an immunosuppressive macrophage phenotype in rats. This study also indicates that measuring T-cell proliferation is as sensitive a marker of NiCl2-induced immunotoxicity as measuring T-cell or macrophage cytokine production. Co-measurement of circulating nickel concentrations and immune parameters yields valuable information with regard to the potency of nickel to alter immune function in vivo. These data also suggest that quite a large quantity of nickel needs to reach the systemic circulation before any adverse effects on immune function are observed.     

Aquilegia vulgaris extract attenuates carbon tetrachloride-induced liver fibrosis in rats

Six groups of male Wistar rats were treated as follows: in groups II, III and V liver damage was induced by CCl₄ (per os, 1590 mg/kg b.w. day) given 2 days a week for 6 weeks; group III was treated simultaneously with ethanol extract of Aquilegia vulgaris (100 mg/kg b.w. day) for 6 weeks; group V with silymarin, positive control, at a dose of 100mg/kg b.w. day for 6 weeks; and groups IV and VI received only the extract or silymarin, respectively. Microsomal lipid peroxidation in the liver increased following CCl₄ treatment by 61–213% and was not changed significantly by the extract. The effect of silymarin was more pronounced, 19–52% decrease in the lipid peroxidation level. Hepatic glutathione was depleted by 22% in CCl₄-treated rats. The extract tested did not change this parameter. The activity of antioxidant enzymes was significantly reduced after CCl₄ administration, by 42–63%. Co-administration of the extract or silymarin resulted in significant increase in these enzymes activity; however, the basal level was not reached. Hepatic hydroxyproline concentration was elevated over 5-fold in comparison with controls. Co-administration of the extract or silymarin decreased the level of hydroxyproline by 66% and 55%, respectively. Activity of serum hepatic enzymes was elevated in rats treated with CCl₄ by 47–8700%. Both the extract and silymarin reduced significantly these enzymes’ activity. The extract caused a fall in bilirubin and cholesterol level in rats treated with CCl₄ by 42% and 17%, respectively. Histopathological examination revealed less-severe fibrosis in rats co-administered the extract or silymarin when compared to animals treated with CCl₄ alone.     

咪达普利对氯化铵所致急性肺损伤大鼠血气、MDA及AngⅡ、CD54蛋白表达的影响

 目的: 本研究通过复制氯化铵致大鼠肺损伤模型,研究咪达普利对肺损伤大鼠动脉血气、MDA、肺形态学和AngⅡ、CD54蛋白表达的影响。方法: 将30只雄性大鼠随机分为3组:空白对照组、肺损伤模型组和药物组。对照组大鼠腹腔注射生理盐水2 mL/kg;肺损伤模型组大鼠腹腔注射等量6%氯化铵;药物组大鼠在注射6%氯化铵后,每天1次灌胃咪达普利(3 mg/kg),连续灌胃7 d;在实验第7天,用2%的戊巴比妥钠麻醉,采集腹主动脉血和腹腔静脉血样本;肺组织经4%多聚甲醛灌注、固定、脱水、透明、浸蜡、包埋和切片。ELISA法测定血清TNF-α和IL-6水平,化学发光法测定血清MDA含量,HE染色观察肺部形态学变化,免疫组织化学染色法观察肺组织AngⅡ和CD54蛋白表达。结果: 与对照组相比,模型组PaCO₂明显升高(P < 0.05),血清TNF-α、IL-6和MDA浓度显著增加(P < 0.01),氯化铵腹腔注射的肺损伤模型组大鼠出现肺水肿、肺炎、肺泡壁瘀血、肺泡腔出血和肺泡壁增生等损伤,肺组织AngⅡ和CD54蛋白表达明显增高(P < 0.01);与模型组比较,药物组PaCO₂明显降低(P < 0.05),血清TNF-α、IL-6和MDA浓度以及肺组织AngⅡ、CD54蛋白表达显著降低(P<0.01)。结论: 咪达普利可显著改善氯化铵所致肺损伤大鼠血气,抑制脂质过氧化和血清炎症细胞因子,降低肺组织AngⅡ和CD54蛋白表达。     

A method for accurate measurement of cutaneous irritancy of trichothecenes

Conventional skin irritation bioassays for trichothecenes are semiquantitative because test animals vary in sensitivity, and the intensity of cutaneous inflammation is poorly correlated with dose. A quantitative bioassay was therefore devised for toxicological studies on the irritancy of trichothecenes. A graded series of six standard solutions of T-2 toxin (10-60 micrograms/mL) in 2 microL volumes was applied to the shaved skin of young female Wistar rats. Each test sample was applied at least twice to each of five rats. After 48 hours, reactions were rated in units of equivalent concentrations of T-2 toxin, so that measurements were independent of the intensity of inflammatory reaction. Mean concentrations of replicate measurements of test solutions of T-2 toxin between 10 and 60 micrograms/mL were precise (SEM less than 1.6 micrograms/mL) and accurate (within 13% of actual concentrations).     

异烟肼灌胃建立小鼠急性肝损伤模型的研究

 目的 探索应用异烟肼灌胃建立小鼠急性肝损伤模型，并初步阐明其机制。 方法 昆明种小鼠 50 只，随机分为异烟肼正常剂量造模组（常量组）、2 倍剂量造模组（2 倍量组）、5 倍剂量造模组（5 倍量组）、8 倍剂量造模组（8 倍量组）和空白对照组，每组各 10 只。各造模组分别以 90、180、450、720 mg/kg 剂量的异烟肼灌胃，18 h 后检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平并取肝组织进行光镜观察，探索导致明显急性肝损伤的相对合适剂量。另取昆明种小鼠 90 只，随机分为单纯造模组（40 只）、干预造模组（40 只）和空白对照组（10 只），各造模组以相对合适剂量异烟肼灌胃，其中干预造模组于造模前以甘利欣75 mg/kg 体重连续灌胃 5 d，18、36、54、72 h 后分别检测血清 ALT、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧物酶（GSH-Px）水平，并进行肝组织光镜和电镜观察，探索导致明显急性肝损伤的相对合适时间及可能机制。 结果 在探索相对合适剂量实验中，2 倍量组小鼠血清ALT、AST 分别为（101.6 ± 6.3）和（108.1 ± 14.9）U/L，明显高于空白对照组的（30.1 ± 3.6）、（35.3 ± 6.5）U/L 和常量组的（52.8 ± 5.3）、（53.9 ± 8.9）U/L，差异均有统计学意义（均P < 0.05），肝细胞出现广泛的脂肪变性和水肿，肝窦几乎消失；5 倍量组小鼠死亡 7 只，8 倍量组小鼠则全部死亡。在探索相对合适时间及发生机制实验中，应用2 倍剂量异烟肼灌胃后 18 h，单纯造模组小鼠血清 ALT、MDA 水平明显高于空白对照组，SOD、GSH-Px 水平明显低于空白对照组，肝细胞广泛损伤，细胞超微结构显著变化。 结论 应用 2 倍剂量（180 mg/kg）异烟肼灌胃可成功建立小鼠急性肝损伤模型。异烟肼所致急性肝损伤可能与自由基脂质过氧化反应密切相关。     

Ethane exhalation after carrageenan-induced pleurisy in rats

Carrageenan-induced pleurisy in rats causes enhanced lipid peroxidation, measured by ethane evolutionin vivo. Ethane evolution was totally inhibited by SOD (100 U/rat), while Se-GSH·Px (100 U/rat) depressed ethane evolution to the basal level, when both enzymes were given intrathoracically 0.5 h after carrageenan.GSH (20 mg/rat) had only slight effects, in contrast to Se-GSH·Px and GSH, injected together, which had no influence on ethane evolution.These effects didn't correlate with other signs of acute inflammation, like exudate volume and leucocyte number, but they do indicate differing significance of reactive oxygen metabolites in and their scavengers on symptoms of inflammation.