Ferulic acid, a natural protector against carbon tetrachloride-induced toxicity

The present work is aimed at evaluating the protective effect of ferulic acid (FA), a naturally occurring phenolic compound on CCl4 induced toxicity. The activities of liver markers (alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase), lipid peroxidative index (thiobarbituric acid-reactive substances, hydroperoxides, nitric oxide, protein carbonyl content), the antioxidant status (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione) were used as biomarkers to monitor the protective role of FA. The liver marker enzymes in plasma and lipid peroxidative index in liver and kidney were increased in CCl4-treated groups, which were decreased significantly on treatment with FA. The antioxidants, which were depleted in CCl4-treated groups, were improved significantly by FA treatment. Administration of FA to normal rats did not produce any harmful effects. Thus our results show that FA is an effective antioxidant without any side-effects and may be a great gain in the current search for natural therapy.     

Caffeic acid alleviates the increased lipid levels of serum and tissues in alcohol-induced [hepatotoxicity in] rats

Ethanol is one of the most widely used and abused drugs that increases lipid levels in human and experimental animals. The objective of this study was to determine the effect of caffeic acid (CA) on alcohol-induced alterations of lipid levels in serum, liver and kindey of Wistar rats. The alcohol toxicity was induced by oral administration of ethanol (7.9 g/kg/bw) for 45 days through intragastric intubation. The elevation in the levels of lipids upon alcohol administration was accompanied by a significant increase in the levels of cholesterol, phospholipids (PL), free fatty acids (FFA) and triglycerides (TG) in serum, liver and kidney. Oral administration of CA (12 mg/kg/bw) to alcohol fed rats significantly decreased the serum and tissue lipid levels to near those of the control rats. In conclusion, our study suggests that oral administration of CA to alcohol fed rats markedly reduced the accumulation of cholesterol, TG, FFA and PL in circulation, liver and kidney.     

Effect of ellagic acid on cyclosporine A-induced oxidative damage in the liver of rats

Cyclosporine A (CsA) is an immunosuppressor, which is most frequently used in the transplant surgery and in the treatment of autoimmune diseases. It has been shown that CsA is able to generate reactive oxygen species and lipid peroxidation, which are directly involved in the CsA nephrotoxicity, hepatotoxicity and cardiotoxicity. This study was undertaken to investigate the protective effect of ellagic acid (EA), a polyphenolic compound against CsA-induced liver injury in male Wistar rats. In this study, CsA was administered orally (25 mg/kg body weight) for 21 days to induce toxicity. EA was administered orally (12.5, 25 and 50 mg/kg body weight) for 21 days along with oral administration of CsA. CsA-induced liver damage was evidenced by increased activities of serum hepatic enzymes namely aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate dehydrogenase with a significant elevation of lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS) and hydroperoxides in the liver. The levels of enzymic antioxidants such as superoxide dismutase, catalase and glutathione-S-transferase and non-enzymic antioxidants (vitamin C, vitamin E and reduced glutathione) were also decreased in CsA-treated rats. Administrations of EA at 50 mg/kg body weight significantly decreased the activities of hepatic marker enzymes compared with other doses of EA (12.5, 25 mg/kg body weight). In addition, the levels of TBARS and hydroperoxides were significantly decreased and the levels of enzymic and non-enzymic antioxidants significant increased on treatment with EA in the liver. The biochemical observation was supplemented by histopathologic examination of liver section. The results of this study indicate that EA might play an important role in protecting CsA-induced oxidative damage in the liver.     

Effect of carvacrol on hepatic marker enzymes and antioxidant status in d-galactosamine-induced hepatotoxicity in rats

Carvacrol (2-methyl-5-(1-methylethyl)-phenol) is a predominant monoterpenic phenol which occurs in many essential oils of the family Labiatae including Origanum, Satureja, Thymbra, Thymus , and Corydothymus species. This study was designed to investigate the hepatoprotective and antioxidant properties of carvacrol on d -galactosamine (D-GalN)-induced hepatotoxicity and oxidative damage in male albino Wistar rats. D-GalN hepatotoxic rats exhibited elevation in the activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and lipidperoxidative markers such as thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides. Activities of enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) and the levels of non-enzymatic antioxidants (vitamin C, vitamin E, and reduced glutathione) in the plasma, erythrocytes, liver, and kidney decreased in the hepatotoxic rats. Oral administration of carvacrol for 21 days brought these parameters towards normal. The biochemical observations were supported by histological studies of rat liver and kidney tissues. These results suggest that carvacrol could afford a significant hepatoprotective and antioxidant effect against D-GalN-induced rats.     

Antioxidant Activity of Coated Probiotic Lactobacillus casei on Chromium(VI) Induced Oxidative Stress in Rats

Experimental study was conducted to evaluate the antioxidant potential of sodium alginate coated probiotic Lactobacillus casei against chromium (VI)-induced oxidative stress in albino rats. Administration of chromium (Cr) VI significantly (p < 0.05) increased the peroxidation markers such as malondialdehyde and protein carbonyls along with significant (p < 0.05) decrease in antioxidant markers such as super oxide dismutase and reduced glutathione in liver and kidney homogenates. Chromium also caused a significant (p < 0.05) alteration in hepatic and renal functional markers in serum viz., total protein, alanine transaminase, blood urea nitrogen and creatinine. Prominent pathological changes observed in liver were vascular congestion, degenerative changes, dilatation of sinusoids and mononuclear cell infiltration, while the kidney showed degeneration of tubular epithelial cells, cystic dilatation of tubules and hyaline casts. Co-administration of coated probiotic L. casei strain 17 reversed the Cr-induced changes.     

Caffeic acid phenethyl ester protects against oxidative stress-related renal dysfunction in rats treated with cyclosporin A

The therapeutic index of cyclosporin A (CsA), an immunosuppressive drug, is limited by its nephrotoxic effect. Oxidative stress is suggested to play a crucial role as pathogenic factors. The present study aimed at investigating the effects of caffeic acid phenethyl ester (CAPE), a phenolic antioxidant, on renal function, morphology, and oxidative stress following CsA treatment. Rats were treated with vehicle, CsA (50 mg/kg), and CsA plus CAPE (10 and 30 μmol/kg) for 10 days. Renal function, histopathology, and tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels were evaluated 24 h after the last treatment. CsA produced nephrotoxicity as indicated by a significant increase in serum creatinine and blood urea nitrogen, but decrease creatinine and urea clearance compared to those treated with vehicle. Severe vacuolations and tubular necrosis were evident in the kidney of CsA-treated rats. CsA also increased renal MDA and decreased GSH content significantly. Administration of CAPE along with CsA restored all the changes caused by CsA. These results clearly demonstrate the pivotal role of oxidative stress and its relation to renal dysfunction and also point to the protective potential of CAPE against CsA nephrotoxicity. The protection afforded by CAPE is mediated, at least in part, through inhibiting renal lipid peroxidation and enhancing or maintaining the antioxidant glutathione content.     

Protective effect of Sesbania grandiflora against erythromycin estolate-induced hepatotoxicity

Sesbania grandiflora, commonly known as 'sesbania', is widely used in Indian folk medicine for the treatment of liver disorders. Oral administration of an ethanolic extract of S. grandiflora leaves (200 mg/kg/day) for 15 days produced significant hepatoprotection against erythromycin estolate (800 mg/kg/day)-induced hepatotoxicity in rats. The increased level of serum enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase), bilirubin, cholesterol, triglycerides, phospholipids, free fatty acids, plasma thiobarbituric acid reactive substances and hydroperoxides observed in rats treated with erythromycin estolate were significantly decreased in rats treated concomitantly with sesbania extract and erythromycin estolate. The sesbania extract also restored the depressed levels of antioxidants to near normal. The results of the study reveal that sesbania could afford a significant protective effect against erythromycin estolate-induced hepatotoxicity. The effect of sesbania was compared with that of silymarin, a reference hepatoprotective drug.     

The evaluation of altered redox status in plasma and mitochondria of acute and chronic diabetic rats

OBJECTIVES: An increase in plasma oxidative stress and decreased mitochondrial lipid hydroperoxides may contribute to the imbalance in the redox status between intramitochondrial and extramitochondrial milieu in chronic experimental diabetic rats. DESIGN AND METHODS: To determine the effect of hyperglycemia in promoting redox imbalance, we determined lipid hydroperoxides (LHP), protein carbonyl (PCO), total antioxidant activity (ferric reducing/antioxidant power; FRAP) and albumin as markers of redox status of plasma, and mitochondrial lipid hydroperoxide levels as a marker of lipid peroxidation in liver, pancreas and kidney tissue of acute and chronic diabetic male Sprague-Dawley rats and their controls. The levels of the studied markers were determined by colorimetric methods. RESULTS: Plasma and mitochondrial oxidative stress parameter levels of acute diabetic rats were not significantly different from their controls. Plasma LHP and PCO levels of chronic diabetic rats were increased significantly as compared to those of both acute diabetic rats and the controls. Plasma FRAP levels of chronic diabetic animals were decreased significantly as compared to those of the controls. On the other hand, LHP levels in liver, pancreas and kidney mitochondria of chronic diabetic rats were decreased significantly as compared to those of both acute diabetic rats and the controls. We observed a negative correlation between LHP levels in liver mitochondria of chronic diabetic rats, and PCO and fructosamine levels in plasma of chronic diabetic rats were correlated. LHP levels in the pancreatic mitochondria of chronic diabetic rats and plasma oxidative stress parameters of chronic diabetic rats were not significantly correlated. LHP levels in kidney mitochondria of chronic diabetic rats were significantly correlated with serum albumin. There was no correlation between LHP levels in kidney mitochondria and other plasma oxidative stress parameters in chronic diabetic rats. CONCLUSIONS: Our data suggest that redox imbalance between plasma and liver mitochondria might become a major threat to chronic diabetic rats.     

Fluvastatin attenuates severe hemorrhagic shock-induced organ damage in rats

Objectives

Multiple organ dysfunction resulting from hemorrhagic shock (HS) and subsequent resuscitation was mediated by several inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10). The present study was designed to investigate the protective effects of fluvastatin on these mediators after HS in rats.

Methods

The experimental rats were randomly divided into three groups. The vehicle group received only vitamin K without HS, the HS-control group received vitamin K and HS, and the HS-experimental group received both vitamin K and fluvastatin (1 mg/kg) before HS. HS was produced by bleeding from a femoral arterial catheter to remove 60% of total blood volume (6 ml/100 g BW) over 30 min. The mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 12 h after the start of blood withdrawal. The biochemical parameters, including arterial blood gas, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and lactate were obtained at 30 min before induction of HS and at 0, 1, 3, 6, 9 and 12 h after HS. Equal volume of normal saline was given to replace blood volume loss. Cytokine levels including TNF-α and IL-10 in serum were measured at 1 h after HS. Kidney, liver, lung and small intestine were removed for pathology examination at 48 h after HS.

Results

HS significantly increased HR, blood GOT, GPT, BUN, Cre, LDH, CPK, lactate, TNF-α and IL-10 levels, and also induced metabolic acidosis and decreased MAP in rats. Pre-treatment with fluvastatin was found to improve survival rate, preserved MAP, decreased the markers of organ injury, suppressed the release of TNF-α and increased IL-10 after HS in rats.

Conclusion

Pre-treatment with fluvastatin can suppress the release of serum TNF-α and can also increase serum IL-10 level to protect HS-induced multi-organ damage in rats.     

Metabolic normalization of alpha-ketoglutarate against N-nitrosodiethylamine-induced hepatocarcinogenesis in rats

Chemoprevention of cancer is one of the reliable approaches to control the incidence of cancer. In the present study, we investigated the chemopreventive role of alpha-ketoglutarate (alpha-KG) during N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. The activities of serum aspartate and alanine transaminases were found to be significantly higher in NDEA + CCl(4)-treated animals when compared with control animals. Administration of alpha-KG restored the activities of transaminases to near normal range. The levels of lipid peroxides, thiobarbituric acid reactive substances were decreased in the liver tissue of NDEA + CCl(4)-treated animals when compared with control animals. alpha-KG reversed the lipid peroxide levels to near normal range. Levels of antioxidants, reduced glutathione and activities of its dependent enzymes, glutathione peroxidase and glutathione-S-transferase were found to be significantly higher in liver tissue of NDEA + CCl(4)-treated animals when compared with control animals. alpha-KG administration positively modulated the antioxidant levels to near normal range. In conclusion, it can be suggested that alpha-KG exerts chemopreventive role which may attributable to its ability to positively modulate the transaminase activities and oxidant-antioxidant imbalance during hepatocarcinogenesis.     

硫代硫酸钠对高磷诱导的残肾大鼠血管钙化早期干预作用的观察

目的 探讨硫代硫酸钠对高磷诱导的残肾大鼠血管钙化的早期干预作用.方法 5/6肾切除大鼠,术后给予高磷或正常磷饮食16周,以高磷饮食制作血管钙化模型.分为5组:假手术+正常磷组(SNP,n=7),假手术+高磷组(SHP,n=7),残肾+正常磷组(NNP,n=7),残肾+高磷组(NHP,n=7),残肾+高磷+硫代硫酸钠治疗组(THP,n=7),治疗组以硫代硫酸钠腹腔注射16周.收集尿量检测24h尿蛋白,取血检测血清钙、磷、肌酐、尿素氮.取胸主动脉,HE和yon kossa染色检测血管钙化,免疫组化分析大鼠胸主动脉Ⅲ型钠磷转运体亚型(Pit-1)、核心结合因子(Cbf α 1)的表达.结果 各组大鼠尿蛋白、尿素氮、肌酐、尿酸和血磷浓度均有明显差别(F值分别为19.057、43.527、26.688、40.324和7.676,P值均＜0.01),NHP组较其他各组明显增高(P＜0.05).HE和von kossa染色显示,NHP组大鼠呈现明显钙化,SNP和SHP组未见明显变化,MP和THP组见散在的钙化点.免疫组化显示,主动脉Pit-1和Cbf α1表达各组有明显差异(F值为8.259和5.91,P＜0.01),其中NHP组表达明显增高(P＜0.01),Pit-1和Cbf α 1阳性面积比与血磷相关性分析显示分别为:r=0.344,P＜0.05和r=0.376,P＜0.05,Pit-1、Cbfα1表达与血磷呈正相关.THP组血清肌酐、尿素氮、尿酸、血磷和尿蛋白均较NHP组明显下降(P＜0.01或＜0.05),其主动脉Pit-1和Cbfα1表达明显减少(P＜0.05),主动脉钙化部分减轻. 结论 高磷饮食喂食残肾大鼠,可成功制作血管钙化模型,硫代硫酸钠早期干预,可明显改善其肾功能,降低血磷,下调动脉Pit-1和Cbf α1表达,减轻血管钙化.     

Inhibitory effect of Hemidesmus indicus and its active principle 2-hydroxy 4-methoxy benzoic acid on ethanol-induced liver injury

The study evaluates the inhibitory activity of ethanolic root extract of Hemidesmus indicus (H. indicus) and its active principle 2-hydroxy 4-methoxy benzoic acid (HMBA) on liver fibrotic markers and characteristics such as collagen content, matrix metalloproteinases (MMPs) 2 and 9 in ethanol-fed rats. Experimental groups were control, H. indicus (500 mg/kg body weight every day during the last 30 days), HMBA (200 microg/kg body weight every day during the last 30 days), alcohol (5 g/kg body weight by intragastric intubation everyday, i.e. throughout the experimental period of 60 days), alcohol plus H. indicus and alcohol plus HMBA. Ethanol administration significantly increased the levels of liver collagen and hydroxy proline content, cross-linked fluorescence, shrinkage temperature and lipid peroxidation and significantly decreased the solubility of liver collagen and the ascorbic acid content when compared with control rats. On treatment with H. indicus and HMBA the ethanol-fed rats showed significantly reduced levels of liver collagen and hydroxyproline content, cross-linked fluorescence, shrinkage temperature and lipid peroxidation and enhanced solubility of liver collagen and ascorbic acid levels when compared with untreated ethanol-fed rats. MMPs were extracted from the liver of control, H. indicus-treated, HMBA-treated, ethanol-administered, ethanol with H. indicus-coadministered and ethanol with HMBA-coadministered rats. The inhibition was analyzed by gelatin zymography and the percentage of expression was determined by a gel documentation system. The activities of MMPs 2 and 9 were significantly increased in ethanol-supplemented rats. Cotreatment of H. indicus/HMBA with ethanol showed significantly decreased activities of these enzymes when compared with those of the untreated rats. H. indicus/HMBA alone treatment showed no such significant alterations. Thus, our present study reveals the strong inhibitory activity of H. indicus and HMBA on the quantitative and qualitative properties of hepatic collagen and also MMPs involved in the extracellular matrix degradation during ethanol intoxication.     

Modulation of pentylenetetrazole-induced seizures and oxidative stress parameters by sodium valproate in the absence and presence of N-acetylcysteine

In view of a role of oxidative stress in epilepsy and the evidence for the involvement of peroxidative injury in sodium valproate (SVP)-induced adverse effects on liver and kidneys, we investigated whether the combination of SVP with N-acetylcysteine (NAC), an antioxidant, may help us to achieve maximal efficacy in terms of seizure control, with minimal toxicity on liver and kidneys. Pentylenetetrazole (PTZ)-induced seizures were used to evaluate the anticonvulsant effect of drugs. Biochemical estimations included the determination of oxidative stress markers like thiobarbituric acid-reactive substances in brain tissue and glutathione (GSH) levels in liver and kidney tissues. Aspartate aminotransferase and alanine aminotransferase concentrations in the serum were also determined to assess liver function. In our study, NAC exhibited a nondose-dependent anticonvulsant effect. The concurrent administration of NAC with SVP significantly prolonged the latency to jerks, myoclonus and clonic generalized seizures. No significant oxidative stress was evident in brain tissue following PTZ-induced seizures, though an elevation of serum transaminase enzymes was seen. SVP at the dose studied did not produce any significant oxidative stress on the liver and kidneys, while treatment with NAC elevated liver and kidney GSH levels. The concurrent administration of NAC with SVP had beneficial effects on liver and kidney cells.     

Effect of vitamin E and vitamin C supplementation on antioxidative state and renal glomerular basement membrane thickness in diabetic kidney

The aim of this study was to analyze the effect of vitamins C and E on malondialdehyde (MDA) content and activities of key antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as glomerular basement membrane (GBM) thickness in streptozotocin-induced diabetic kidney in rats. Wistar male rats were divided into following groups (12 rats each): the control, diabetic rats, diabetic rats whose drinking water was supplemented with vitamin C in a dose of 1.0 g/l or diet was supplemented with 200 mg of vitamin E/100 g fodder. Body weight, blood glucose and HbA1C levels and 24-hour urinary albumin excretion (UAE) were studied every week (0-12 weeks). After 6 and 12 weeks, MDA content and activities of SOD, CAT and GSH-Px were measured in the kidney homogenate supernatants. Electron micrographs of glomeruli were scanned and morphometric investigations were performed by means of computer image analysis system to compare GBM thickness. The blood glucose and HbA1C concentrations and UAE in diabetic rats were significantly higher than in the control group. An increase in the MDA level and decrease in the SOD, CAT and GSH-Px activities in the kidney of diabetic rats were observed after 6 and 12 weeks of experiment. Administration of vitamins C and E did not affect body weight, blood glucose and HbA1C levels. Both vitamin C and vitamin E decreased lipid peroxidation and augmented the activities of antioxidant enzymes studied in the kidneys of diabetic rats as well as reduced UAE, decreased kidney weight and GBM thickness. The results indicate the potential utility of antioxidant vitamins in the protection against the development of diabetic nephropathy.     

Chlorogenic acid a dietary polyphenol attenuates isoproterenol induced myocardial oxidative stress in rat myocardium: An in vivo study

Intent of the present study has been made to appraise the cardioprotective effect of chlorogenic acid (CGA) on isoproterenol (ISO) induced myocardial infarction (MI) in male albino Wistar rats. ISO-induced myocardial damage was indicated by the elevated levels of marker enzymes such as creatine kinase (CK), creatine kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and troponin T and I (cTnT, cTnI) in the serum. In addition, the levels of lipid peroxidation products such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LHPs) were significantly increased in the plasma and heart tissue. Activities of enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the non enzymic antioxidants like vitamin C, vitamin E and reduced glutathione (GSH) were decreased in the erythrocytes, plasma and heart tissue of the ISO-induced rats and myocardium infarct size as observed by staining with triphenyltetrazolium chloride (TTC). Histopathological observation corroborated with the bioochemical parameters. Oral administration of CGA at different doses (10, 20, 40 mg/kg BW) for 19 days prevented the above changes. The 40 mg/kg BW of CGA was more pronounced than other two doses and brought back all the above parameters to near normalcy.     

感染HBV或HCV的肝病患者血清半胱氨酸蛋白酶抑制剂C的改变

目的探讨血清半胱氨酸蛋白酶抑制剂C（Cystatin C）在感染HBV或HCV肝病患者中的临床应用。方法测定了207例HBV或者HCV感染的肝病患者和32名健康对照组（H组）中Cystatin C和金属蛋白酶组织抑制剂（TIMPs）浓度。肝病患者被分成肝硬化组（A组，67例）、慢性乙肝组（B组，73例）、慢性丙肝组（C组，39例）和肝癌组（D组，28例）。结果受试者Cystatin C、TIMP-1和TIMP-2在各组间差异均有统计学意义（F值分别为28．234、128．091、196．549，P值均〈0．001）。Cystatin C与TIMPs在各肝病组中的变化一致：肝病组均显著高于健康对照组，A组和D组均显著高于B组与C组，A组与D组、B组与C组间均差异无统计学意义。Pearson相关分析显示Cystatin C与TIMP-1在各肝病组中均呈明显正相关，且有显著性差异；但Cystatin C与TIMP-2的相关性仅A组（r=0．269，P〈0．05）和D组（r=0．398，P〈0．05）呈正相关，有显著性差异，而B组（r=-0．102，P〈0．05）和C组（r=-0．107，P〈0．05）则呈负相关，且差异无统计学意义。结论血清胱抑素C可能是监测肝脏功能的有用指标。     

Protective effects of vitamin C, alone or in combination with vitamin A, on endotoxin-induced oxidative renal tissue damage in rats

This study was designed to investigate the protective effects of vitamin C and vitamin A on oxidative renal tissue damage. Male Wistar rats were given an intraperitoneal injection of 0.5 ml saline (control) or 0.5 ml solution of lipopolysaccharide (10 mg/kg), which caused endotoxemia. Immediately (within 5 min) after the endotoxin injection, the endotoxemic rats were untreated or treated with intraperitoneal injection of vitamin A (195 mg/kg bw), vitamin C (500 mg/kg bw) or their combination. After 24 hours, tissue and blood samples were obtained for histopathological and biochemical investigation. Endotoxin injection caused renal tissue damage and increased erythrocyte and tissue malondialdehyde (MDA) and serum nitric oxide (NO), urea and creatinine concentrations, but decreased the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities compared to the parameters of control animals. Treatment with vitamin C or with vitamins C and A significantly decreased the MDA levels and serum NO, urea and creatinine levels, recovered the antioxidant enzyme activities (SOD, GSH-Px and CAT), and prevented the renal tissue damage in endotoxemic rats. In contrast, vitamin A alone did not change the altered parameters except for creatinine levels. Notably, the better effects were observed when vitamins A and C given together. It is concluded that vitamin C treatment, alone or its combination with vitamin A, may be beneficial in preventing endotoxin-induced oxidative renal tissue damage and shows potential for clinical use.     

3项肾小球滤过率内源性标志物的临床应用评价

目的 探讨3项肾小球滤过率内源性标志物的临床应用价值.方法 测定57例肾脏疾病患者和50例健康人的血清Cystatin C、β2微球蛋白(β2-M)、血清肌酐(Scr)及尿肌酐浓度,计算Ccr值后进行统计分析.结果 当肾脏有轻微损伤时,Cystatin C出现明显变化,血清β2-M、Scr与健康对照组相比差异无统计学意义;3项肾小球滤过率内源性标志物与Ccr之间均呈高度负相关,血清Cystatin C与Ccr相关性的密切程度高于其他两者.结论 血清Cystatin C的敏感性、特异性优于Scr和血清β2-M,是GFR最理想的内源性标志物,应纳入肾功能常规检查.     

Chronic cold exposure affects the antioxidant defense system in various rat tissues

BACKGROUND: Chronic exposure to stress alters the normal body homeostasis and, hence, leads to the development of various human pathologies, which might involve alterations in the antioxidant defense system. We studied the effect of chronic cold exposure on oxidative stress and antioxidant defense system in various rat tissues. METHODS: Male albino rats (Wistar strain), 2-3 months old, were exposed to 3 weeks of cold treatment. Antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) were measured in addition to the antioxidants, ascorbic acid (AsA) and glutathione (GSH), and the prooxidants, lipid peroxides (LPO) and xanthine oxidase (XOD), in brain, heart, kidney, liver and small intestine using standard protocols. RESULTS: Chronic cold exposure resulted in a significant increase in LPO in all the tissues studied while XOD was increased in the brain and intestine. Total SOD activity was significantly decreased in all the tissues, whereas CAT activity was significantly increased in the kidney and decreased in heart, liver and intestine in the animals exposed to cold. GPx activity was increased only in the brain and intestine of stressed rats. Chronic cold exposure resulted in significant decrease in GR activity in heart, liver and intestine. GST activity was increased (except heart) and GSH was significantly decreased in all the tissues in treated rats. AsA was increased in kidney and intestine but decreased in heart of stressed animals. CONCLUSIONS: The observed changes in the antioxidant defense system are tissue specific, but it is evident that chronic exposure to cold leads to oxidative stress by displacing the prooxidant-antioxidant balance of this defense system by increasing the prooxidants while depleting the antioxidant capacities.     

Low in vivo toxicity of a novel cisplatin-ursodeoxycholic derivative (Bamet-UD2) with enhanced cytostatic activity versus liver tumors

Cisplatin-bile acid derivatives belonging to the Bamet-family maintain both liver organotropism and cytostatic activity. "In vivo" toxicity and usefulness as chemotherapeutic agent versus liver tumors of a novel drug, Bamet-UD2 [cis-diamminechlorocholylglycinate platinum (II)], with enhanced "in vitro" cytostatic activity was investigated. Using orthotopically implanted mouse Hepa 1-6 hepatoma in the liver of Nude mice, the antitumor effect of Bamet-UD2 was compared with that of a previously characterized compound of this family, Bamet-R2 [cis-diamminebis-ursodeoxycholate platinum(II)], and cisplatin. Life span was significantly prolonged in mice treated with both Bamets (Bamet-UD2 > Bamet-R2), compared with animals receiving saline or cisplatin. All these drugs inhibit tumor growth (Bamet-UD2 = cisplatin > Bamet-R2). However, toxicity-related deaths only occurred under cisplatin treatment. Using rats maintained in metabolic cages, organ-specific toxicity and drug accumulation in tissues were investigated. The amount of both Bamets in the liver was severalfold higher than that of cisplatin. By contrast, a significantly higher amount of cisplatin in kidney and nerve was found. In lung, heart, muscle, brain, and bone marrow the amount of drug was small and also significantly lower in animals receiving Bamets. Signs of neurotoxicity (altered nerve conduction velocity), nephrotoxicity (increased serum urea and creatinine concentrations and decreased creatinine clearance), and bone marrow toxicity (decreased platelet and white blood counts) in animals treated with cisplatin but not with the Bamets were found. These results indicate that, owing to strong antitumor activity together with absence of side effects, Bamet-UD2 may be useful in the treatment of liver tumors.