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1.
急危重症眼镜蛇伤大鼠多项凝血指标动态变化   总被引:1,自引:1,他引:0  
杨嘉琳  孔天翰 《蛇志》2010,22(3):198-202
目的动态观察蛇伤后大鼠多项凝血指标、病理及皮下出血情况的改变,为蛇毒毒理及抗蛇毒制剂的研究提供实验数据。方法将SD大鼠注入2~4 LD50眼镜蛇毒造模,于注毒后不同时段(20~140 min)分别进行凝血功能、肝脏和肾脏病理等检测,处死大鼠后观察注毒部位皮下出血情况。结果大鼠注入4 LD50蛇毒20 min,凝血酶原时间(PT)、部分凝血酶原时间(APTT)延长;40 min时,纤维蛋白原(Fbg)明显下降;40 min后凝血功能逐渐回复至0 min水平。肾脏、肝脏组织见血管扩张、充血明显。注毒部位皮下出血范围于20~80min时最明显。2 LD50剂量组凝血功能的变化与4 LD50组相似,但其Fbg下降程度小于4 LD50组,皮下出血面积较4 LD50组小。结论眼镜蛇毒引起凝血功能改变,且其变化程度与剂量及注入时间密切相关。  相似文献   

2.
This study was designed to elucidate the toxicity of the widely used plant Aegle marmelos in rats. We have taken total alcoholic, total aqueous, whole aqueous and methanolic extracts isolated from the leaves of A. marmelos and studied their toxic effects. Acute, subacute and LD(50) values were determined in experimental rats. The dead animals were obtained from primary screening studies, LD(50) value determination experiments and acute studies subjected to postmortem studies. The external appearance of the dead animals, the appearance of the viscera, heart, lungs, stomach, intestine, liver, kidney, spleen and brain were carefully noted and any apparent and significant features or differences from the norm were recorded. Following the chronic administration of A. marmelos for 14 days, the vital organs such as heart, liver, kidney, testis, spleen and brain were carefully evaluated by histopathological studies and any apparent and significant changes or differences from the norm were studied. From the acute administration of A. marmelos, the LD(50) values were determined using graphical method. The hearts stopped in systolic stand-still in the acute experiments. There were no remarkable changes noticed in the histopathological studies after 50 mg/kg body wt of the extracts of A. marmelos when administered intraperitoneally for 14 days successively. Pathologically, neither gross abnormalities nor histopathological changes were observed. After calculation of LD(50) values using graphical methods, we found a broad therapeutic window and a high therapeutic index value for A. marmelos extracts. Intraperitoneal administration of the extracts of the leaves of A. marmelos at doses of 50, 70, 90 and 100 mg/kg body wt for 14 consecutive days to male and female Wistar rats did not induce any short-term toxicity. Collectively, these data demonstrate that the extracts of the leaves of A. marmelos have a high margin of drug safety.  相似文献   

3.
Nitrosoamines such as N-nitrosodiethylamine (NDEA) produce oxidative stress due to generation of reactive oxygen species and may alter antioxidant defence system in the tissues. NDEA was administered ip as a single dose to rats in LD50 or in lower amounts and the animals were sacrificed after 0-48 hr of treatment. The results showed that lipid peroxidation in liver increased, however no significant increase in kidney LPO was observed after NDEA administration. Superoxide dismutase (SOD) and glutathione reductase (GSH-R) activity increased in liver, however, catalase (CAT) activity in liver was inhibited in NDEA treated rats. Kidney showed an increase in SOD activity after an initial decrease along with increase in GSH-R activity in NDEA treated rats. However, kidney CAT activity was not significantly altered in NDEA intoxicated rats. Serum transaminases, serum alkaline phosphatase blood urea nitrogen, serum creatinine and scrum proteins were elevated in NDEA treated rats. The results indicate NDEA-induced oxidative stress and alteration in antioxidant enzymes in liver and kidney to neutralise oxidative stress.  相似文献   

4.
It has been shown that some cytochrome P450-dependent enzyme activities could present daily fluctuations, particularly CYP3A isoenzymes which are enhanced during the dark period. The aim of this study was to investigate whether age and photoperiodic conditions at different circadian stages could influence these fluctuations. Young mature (10 weeks) and old (22 months) Wistar rats were initially exposed to light-dark cycles 12:12 during 4 weeks, and secondly 18:6 for either one week or six weeks. Erythromycin N-demethylase (CYP3A-dependent), 7-ethoxycoumarin O-deethylase (CYP1A-dependent) and aniline 4-hydroxylase (CYP2E-dependent) activities were determined in liver and kidney microsomes at different hours after darkness onset (HADO). In addition, liver and kidney GSH, GSHPx, ATP, TBARS were determined. During the LD 12:12 cycle, while no significant modification was observed in CYP1A- and 2E-dependent enzyme activities as functions of HADO, erythromycin N-demethylase activity (CYP3A-dependent) showed a significant increase during the second third of the dark period in both young and old rats. After switching to a LD 18:6 cycle, this variation was still observed during second third of the dark period, to a lesser but still significant degree, with no difference between one week and six weeks exposure to the new photoperiod. It can be noted that the old rats showed a significantly lower level of erythromycin N-demethylase activity than the young rats, in parallel to a decrease in GSH, GSHPx and ATP, and an increase in TBARS.These results confirm the lower resistance of old animals to oxidative stress. The observed variations in metabolism parameters underline the need for study designs in pharmaco-toxicology taking into account the possible risks induced by circadian changes, especially in aged subjects.  相似文献   

5.
Histopathological, histochemical and biochemical investigations were performed on the brain, sciatic nerve, skeletal muscle, heart, liver and kidney of rats which were given 5% of LD50 dose of DFP for 10 days. A decrease in AChE activity, degeneration of neurons and necrotic changes in the nuclei of hypothalamus, degeneration of myelin sheaths in sciatic nerve, a decrease in succinic dehydrogenase activity in the myocardium, and a minimal decrease of acid phosphatase activity (AcPh) in the liver were found. The biochemical determination of AChE level indicated about 30% AChE activity in erythrocytes and tibialis muscle, and 40% in the brain 1 hr after the last dose of the inhibitor and 80% and 50% respectively on the 7th day after poisoning in relation to normal values.  相似文献   

6.
Soybean protein isolate (SPI) was digested with protease to produce a peptides containing the low-molecular fraction (LD3) or a mixture of high- and low-molecular fractions (HD1). Rats were fed a diets containing SPI, LD3, or HD1 at a protein level equivalent to the 20% casein diet for 4 weeks. The serum triglyceride concentration was lower in rats fed SPI, LD3, and HD1 diets than in rats fed the casein diet, and the differences were significant for the cholesterol-enriched diet. The value for the LD3 group was the lowest among all groups for both the cholesterol-free and -enriched diets. The level of triglyceride in the post-perfused liver was significantly lower in the LD3 and HD1 groups and the SPI group than in the casein group irrespective of the presence of cholesterol in the diet. In the cholesterol-free diet, LD3 feeding as compared to casein feeding caused a reduction in triglyceride secretion from the liver to perfusate and an increment of hepatic ketone body production. The addition of cholesterol to the diets somewhat attenuated these effects of LD3. These results suggest that the low-molecular fraction in soybean peptides causes triglyceride-lowering activity through a reduction in triglyceride secretion from the liver to the blood circulation and the stimulation of fatty acid oxidation in the liver. There is a possibility that soybean peptides modulate triglyceride metabolism by changes in the hepatic contribution.  相似文献   

7.
Jatropha mollissima is one of the ancient plants that known in Africa, Asia and Latin America for its high medicinal value. Previously we showed that the ethanolic leaves extract of J. mollissima was able to reverse the aminoglycoside antibiotics induced nephrotoxicity in only two weeks of administration. Here, we evaluated the phytochemicals, antioxidant and in vivo cytotoxicity of the ethanolic leaves extract in addition to the ability of reversing Cisplatin-induced nephrotoxicity in wistar albino rats. The results of phytochemical analysis showed the presence of flavonoids, phenols, tannins and saponins, with significantly high antioxidant activity. The treated rats did not show any cytotoxic signs; no anatomical, physiological and/or histopathological changes compared with the control group. Kidney, spleen and liver tissues appeared normal after two weeks administration of the maximum dose, with a possible alteration in distal tubules, proximal tubules and glomerulus of the kidney tissues. The results of nephrotoxicity and kidney function suggest promising potential for J. mollissima in kidney damage treatment.  相似文献   

8.
高原鼠兔(Ochotona curzoniae)作为青藏高原高寒草地生态系统中的关键物种,其种群数量随着过度放牧导致的草地退化而暴发式增长。阐明此过程中高原鼠兔天然免疫能力及肝脏和肾脏器官指数的变化,对深入揭示青藏高原草地退化引起的高原鼠兔种群暴发机理具有重要意义。本研究在青海海北高寒草地生态系统国家野外科学观测研究站地区,调查了轻度、中度、重度退化草地中高原鼠兔洞口数量,并测定了成体高原鼠兔血清总IgG含量、肠道寄生物感染状况及肝脏和肾脏指数。结果发现:随着草地退化,高原鼠兔洞口数量和血清总IgG水平显著增加;绦虫和线虫的感染率和感染强度以及肝脏和肾脏指数均显著降低。雄性对绦虫的感染率和肝脏指数显著低于雌性;雌性在重度退化草地中对绦虫和线虫的感染率及感染强度显著低于轻度退化草地。以上结果表明,过度放牧介导的草地退化增强了高原鼠兔的天然免疫功能,缓解了毒素对肝脏和肾脏的损伤,进而可能促进其种群暴发式增长。  相似文献   

9.
The effect of retinyl palmitate on the polyunsaturated fatty-acid composition, chemiluminescence and peroxidizability index of microsomes and mitochondria obtained from rat liver, kidney, brain, lung and heart, was studied. After incubation of microsomes and mitochondria in an ascorbate Fe++ system (120 min at 37 degrees C) it was observed that the total cpm/mg protein originated from light emission: chemiluminescence was lower in liver microsomes, mitochondria and kidney microsomes in the vitamin A group than in the control group. In mitochondria obtained from control rats, the most sensitive fatty acids for peroxidation were arachidonic acid C20:4 n6 in liver and docosahexaenoic acid C22:6 n3 in kidney and brain. In microsomes obtained from control rats, the most sensitive fatty acids for peroxidation were linoleic acid C18:2 n6 and C20:4 n6 in liver and C22:6 n3 in kidney. Changes in the most polyunsaturated fatty acids were not observed in organelles obtained from lung and heart. As a consequence the peroxidizability index, a parameter based on the maximal rate of oxidation of fatty acids, showed significant changes in liver, kidney and brain mitochondria, while in microsomes changes were significant in liver and kidney. These changes were less pronounced in membranes derived from rats receiving vitamin A. Our results confirm and extend previous observations that indicated that vitamin A may act as an antioxidant protecting membranes from deleterious effects.  相似文献   

10.
Subacute doses (1/20 LD50) of aflatoxin B1 and ochratoxin A were fed to weanling albino rats individually and in combination for 36 weeks and then rats were maintained on toxin free normal diet for a period of 24 weeks. Livers of rats were fatty, wherever aflatoxin was administered but the enzyme activity did not show significant differences among various groups. However, in a few individuals whose livers were severely affected, higher concentrations of urine creatinine, liver RNA and DNA, and ALT enzyme activity were recorded. Histopathological examination showed various stages of hepatoma and hepatocarcinoma including nodular hyperplasia, hypertrophy, vacuolisation, degeneration, pseudolobulation, cellular infiltration and fibrosis of liver of rats fed with aflatoxin individually and in combination. Few anaplastic cells in the corticomedullary region and nuclear enlargement of proximal tubular epithelium of kidney were found wherever combined toxin and ochratoxin alone were administered. Liver tumor expression was time dependent.  相似文献   

11.
OBJECTIVES: Free radical scavengers can protect against the genotoxicity induced by chemical carcinogens by decreasing oxidative stress. The protective effect of the antioxidant melatonin was studied in the kidney and liver of rats treated with the kidney-specific carcinogen potassium bromate (KBrO(3)). The major endpoint of oxidative damage measured in this report was lipid peroxidation. METHODS: Four groups of male rats (controls, melatonin-injected [10 mg/kg x4], KBrO(3)-injected [100 mg/kg], and melatonin+-KBrO(3)) were used in the current study. The concentrations of malondialdehyde (MDA) were assayed as an index of oxidatively damaged lipid in the kidney and liver. RESULTS: Twenty-four hours after KBrO(3) administration, MDA levels were significantly increased in the kidney while the increase in the liver was not statistically significant compared to levels in control rats. The percentage increases in lipid peroxidation products were 32.8% and 12.6% for the kidney and liver, respectively. In rats given melatonin 30 minutes before KBrO(3), and three more times after KBrO(3) (i.e., every 6 hours), the increase in MDA levels was reduced in the kidney. Histopathological examination demonstrated marked changes in the structure of the kidney and slight changes in the liver. In the kidney, microscopic examination revealed atypical tubules, atypical hyperplasia, hyaline droplet degeneration, necrotic changes and stratified squamous cell metaplasia. Again, melatonin treatment inhibited the tissue damage associated with KBrO(3) administration. CONCLUSION: These results show that melatonin as an antioxidant and free radical scavenger can prevent oxidative stress induced by the carcinogen KBrO(3).  相似文献   

12.
The effect of carminomycin on the liver energetic metabolism was studied experimentally on rats in dynamics after its intraperitoneal administration in a single LD50 and the therapeutic doses for a treatment course. It was found that changes in the rat liver tissues on the part of the energetic metabolism occurred irrespective of the antibiotic dose and the administration multiplicity. Mainly they were of reversible nature: the balance of consumption and resynthesis of the phosphate macroergs was impaired, the glycolytic processes increased, shifts in the activity of the enzymes of the pentose phosphate pathway of oxydation were observed. The level of the above changes was more pronounced when carminomycin was administered in LD50. The adrenal system played an important role in the mechanism of the shifts noted.  相似文献   

13.
This study reports age-related changes in 7 element (iron, copper, zinc, manganese, mercury, cadmium and lead) concentrations in the liver, kidney and brain of male and female Sprague-Dawley rats from 1 to 364 days of age. Atomic absorption spectrometry was used for the measurements. Copper, mercury and cadmium in the male and female kidneys increased from weaning until 127 days of age, as did iron concentrations in the female liver and kidney. After 127 days, especially, the copper concentration in the female kidney and cadmium concentration in the male and female kidney increased further. Consistent and statistically significant (P less than 0.05) sex differences in element concentrations were found for three elements (iron, copper and zinc). Except for the zinc concentration in the liver from 50 to 72 days, iron (in liver and kidney), zinc (in kidney) and copper (in liver, kidney and brain) concentrations in female rats during the adult stage, were all higher than those of male rats. Isolated differences for other elements (manganese, mercury and cadmium) were also found. The data will be helpful when setting up long-term animal investigations of the biological effect of elements.  相似文献   

14.
Within the lethal dose range, 8.70 mmol/ml ethanol (EtOH, LD50 = 226 mmol/kg) and 6.86 mmol/ml styrene (ST, LD50 = 77.4 mmol/kg) had an additive effect in rats. A four-week pretreatment with 1/10 of the LD50 of the corresponding combination partner did not modify the lethal dose effect of the subsequently administered substance (EtOH or ST). Subchronical treatment with EtOH and ST had an additive effect, too but produced no cumulative effect in relation to lethality. Unlike EtOH, subchronical treatment with ST caused severe symptoms of illness, decrease in body weight and liver lesions. Histological examination at the combined application of EtOH plus ST showed no evidence of qualitatively or intensified effects. Subchronic administration of 1/10 of the LD50-ies of EtOH and ST produced in rats more pronounced histological liver changes than single application of the corresponding LD16-ies. Except for ATP'ase activity, histochemical reactions following EtOH or ST application showed minimal quantitative differences.  相似文献   

15.
In acute toxicity study, rats showed dose-dependent signs of cholinergic hyperactivity and behavioural alterations. Maximum intensity of symptoms was not associated with mortality. Oral LD50 was 1681 mg/kg. In subacute toxicity study, rats were orally administered 50, 100 or 200 mg/kg of anilofos once daily for 28 days. Signs and symptoms were observed mainly with 200mg/kg. At this dose, anilofos induced hypothermia and progressive weight loss. None of the anilofos-treated rats died. Weight of brain, lung, testis was not altered, while of liver, heart, spleen and kidney increased. Anilofos inhibited cholinesterase (ChE) activities of erythrocyte (41-67%), plasma (36%), blood (37-64%), brain (63-73%) and liver (28-48%). Total protein was decreased in plasma and liver. Results indicate moderate toxic potential of anilofos in mammals, substantial contribution of CNS-mediated effects in causing anilofos toxicity and no direct relationship between hypothermia and level of ChE inhibition.  相似文献   

16.
Melatonin (MEL) displays antioxidant and free radical scavenger properties. In the present study, the effect of MEL on the oxidative stress induced by ochratoxin A (OTA) administration in rats was investigated. Four groups of 15 rats each were used: controls, MEL-treated rats (5 mg/kg body mass), OTA-treated rats (250 μg/kg) and MEL+OTA-treated rats. After 4 weeks of treatment, the levels of malondialdehyde (MDA), a lipid peroxidation product (LPO) were measured in serum and homogenates of liver and kidney. Also, the levels of glutathione (GSH), and activities of glutathione reductase (GR), glutathione peroxidase (GSPx), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in liver and kidney were determined. In OTA-treated rats, the levels of LPO in serum and in both liver and kidney were significantly increased compared to levels in controls. Concomitantly, the levels of GSH and enzyme activities of SOD, CAT, GSPx and GR in both liver and kidney were significantly decreased in comparison with controls. In rats received MEL+OTA, the changes in the levels of LPO in serum and in liver and kidney were not statistically significant compared to controls. Concomitantly, the levels of GSPx, GR and GST activities in both liver and kidney tissues were significantly increased in comparison with controls. Similar increases in GSPx, GR and GST activities were also observed in MEL-treated rats when compared with controls. In conclusion, the oxidative stress may be a major mechanism for the toxicity of OTA. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and stimulation of GST activities. Thus, clinical application of melatonin as therapy should be considered in cases of ochratoxicosis.  相似文献   

17.
Summary Although the regulatory activity of steroid hormones on amino acid metabolism has been described, no information is published on the effect of ovariectomy. We studied the influence of ovariectomy in Wistar rats determining the amino acids phenylalanine and tyrosine in liver, kidney, plasma and urine. 32 animals were used in the study, 12 animals were sham operated, 9 animals were ovariectomized and 11 rats were ovariectomized and supplemented with estradiol. No quantitative changes were detected comparing liver and kidney phenylalanine and tyrosine between the groups (sham operated rats liver phenylalanine 2,53nM/mg ± 1,07; liver tyrosine 1.95nM/mg ± 0.92; kidney phenylalanine 2.16nM/mg ± 0.53; kidney tyrosine 1.80nM/mg ± 0.39. Ovariectomized rats showed liver phenylalanine 3.07nM/mg ± 1.14; liver tyrosine 2.63nM/mg ± 1.01; kidney phenylalanine 2.30 nM/mg ± 0.74; kidney tyrosine 1.93nM/mg ± 0.63. Ovariectomized and estradiol supplemented rats presented with liver phenylalanine 2.84nM/mg ± 1.40; liver tyrosine 2.35nM/mg ± 1.28; kidney phenylalanine 1.91nM/mg ± 0.26, kidney tyrosine 1.67nM/mg ± 0.23.). When, however, the phenylalanine/tyrosine ratio in the liver was evaluated, ovariectomized rats showed a significant decrease of the quotient (p = 0.001). The phenylalanine/tyrosine ratio was restored by estradiol replacement. Our findings show that phenylalanine and tyrosine metabolism is under estradiol control. The effect on the metabolic changes could be mediated by enzyme systems as phenylalanine hydroxylase, tyrosine hydroxylase and tyrosine aminotransferase. Our results would be compatible with previous reports on the stimulatory effect of estradiol on these enzymes. The kidney phenylalanine/tyrosine ratio was unaffected by ovariectomy and/or estradiol replacement which can be easily explained by different pools, enzyme activities, filtration/reabsorption effects, etc.The urinary P/T ratio was decreased by ovariectomy and restored by estradiol replacement indicating endocrine control of renal reabsorption and secretion mechanisms.  相似文献   

18.
Nodera M  Yanagisawa H  Wada O 《Life sciences》2001,69(14):1639-1649
Zinc deficient rats were prepared to investigate histopathological changes in thymus, testis, skin, esophagus, kidney and liver and the relationship between these changes and apoptosis. Seven-week-old male SD rats were given a Zn deficient diet (0% Zn diet) or a standard diet (0.02% Zn diet). The above-mentioned organs were excised 1, 2, 3, 4, 5, 10, 13, and 34 weeks after initiating diet administration. Then, these organs were examined morphologically, and apoptotic changes were analyzed by either the TdT- mediated dUTP - biotin nick end labeling (TUNEL) or electrophoresis. Significant morphological changes were seen only in rats on the 0% Zn diet. After 4 weeks, atrophy of the thymus was seen. After 5 weeks, oligospemia was observed, and after 10 weeks, testicular atrophy accompanied by the loss of sperm cells and spermatocytes was confirmed. In addition, after 10 weeks, thickening of epithelia was seen in the skin and esophagus of rats on the 0% diet. During the observation period, no marked morphological changes were observed in the liver or kidney. In the thymus and testis of rats on the 0% Zn diet, prior to detecting any morphological changes, increases in apoptosis were confirmed at 1 and 3 weeks after initiating diet administration, respectively. In the kidney and liver, TUNEL positive cells appeared after 13 and 34 weeks, respectively. These observations suggest that the functional and morphological changes in the thymus and testis of rats on the 0% Zn diet are caused by increased apoptosis, and that even when the supply of Zn is terminated for only a short period of time, immunocytes and germ cells can not survive or regenerate sufficiently. Again, the fact that even in the liver and kidney, apoptosis was observed when administration of the 0% Zn diet was prolonged suggests that the appearance of apoptosis is dependent on the amount of Zn in tissues. In addition, the fact that increases in apoptosis were confirmed in the skin of rats on the 0% Zn diet, but not in the esophagus of these rats suggests that apoptosis does not directly cause thickening of stratified squamous epithelium in Zn deficient rats.  相似文献   

19.
Previous studies have demonstrated marked alterations in trace metal metabolism in male Sprague-Dawley rats following chemical induction of the diabetic state. To determine whether such changes represented a general response to the insulin-deficient condition the levels of zinc, copper, and maganese in liver, kidney, and intestine of normal and streptozotocin (STZ)-diabetic male rats of the Sprague-Dawley, Wistar, and Long-Evans strains, female Sprague-Dawley rats, and male mice were measured. Significantly increased concentrations of zinc, copper, and maganese in liver, and zinc and copper in kidney were found in STZ-diabetic rats, regardless of sex and strain. In contrast, the zinc and copper contents in liver and kidney of control and STZ-diabetic mice were similar, but hepatic manganese levels were significantly elevated in both organs of the diabetic mouse. The concentrations of all three metals were similar in the intestine of control and diabetic rodents. Higher amounts of zinc and copper were bound to metallothionein in the liver and kidney of the diabetic rats. Nicotinamide injection prior to STZ administration protected rats against the development of diabetes and alterations in trace metal status. These data indicate that specific alterations in the metabolism of zinc, copper and manganese during episodes of pancreatic hormonal imbalance represent a general phenomenon in the rat. A possible explanation for the differential response of the STZ-diabetic mouse is discussed.  相似文献   

20.
苦瓜皂甙降血糖作用及其机制初探   总被引:41,自引:0,他引:41  
将雄性Wistar鼠 (体重 1 80± 1 0g)随机分为正常对照组 (NC)、实验对照组 (EC)和两个实验组 (E1、E2 ) ,其中NC、EC组饮用普通水 ,E1、E2组饮用水中分别含有苦瓜皂甙 1 0 0mg·L 1和 2 0 0mg·L 1。饲养五周后 ,后三组动物禁食 2 4h后取血待测 ;取血完毕即开始进食 ,2 4h后再次取血待测。一周后杀死动物取肌肉、肝脏标本检测糖原水平。结果显示苦瓜皂甙虽不影响禁食大鼠血浆胰岛素含量 ,却可明显升高血糖和皮质醇水平 ;显著降低进食后大鼠血糖和胆固醇水平 ,并维持适度的皮质醇水平。肌糖原和肝糖原含量明显增加  相似文献   

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