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排序方式: 共有257条查询结果,搜索用时 16 毫秒
1.
Pınar Erkekoglu Belma Giray Walid Rachidi Isabelle Hininger‐Favier Anne‐Marie Roussel Alain Favier Filiz Hincal 《Environmental toxicology》2014,29(1):98-107
Di(ethylhexyl)phthalate (DEHP), the most widely used plasticizer, was investigated to determine whether an oxidative stress process was one of the underlying mechanisms for its testicular toxicity potential. To evaluate the effects of selenium (Se), status on the toxicity of DEHP was further objective of this study, as Se is known to play a critical role in testis and in the modulation of intracellular redox equilibrium. Se deficiency was produced in 3‐weeks‐old Sprague–Dawley rats feeding them ≤0.05 mg Se /kg diet for 5 weeks, and Se‐supplementation group was on 1 mg Se/kg diet. DEHP‐treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S‐transferase (GST); concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), and thus the GSH/GSSG redox ratio; and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP was found to induce oxidative stress in rat testis, as evidenced by significant decrease in GSH/GSSG redox ratio (>10‐fold) and marked increase in TBARS levels, and its effects were more pronounced in Se‐deficient rats with ~18.5‐fold decrease in GSH/GSSG redox ratio and a significant decrease in GPx4 activity, whereas Se supplementation was protective by providing substantial elevation of redox ratio and reducing the lipid peroxidation. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting testicular tissue from the oxidant stressor activity of DEHP. © 2011 Wiley Periodicals, Inc. Environ Toxicol 29: 98–107, 2014. 相似文献
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3.
Julie K. Klint Géza Berecki Thomas Durek Mehdi Mobli Oliver Knapp Glenn F. King David J. Adams Paul F. Alewood Lachlan D. Rash 《Biochemical pharmacology》2014
Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (CaV) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-Cc1a (Cc1a), from the venom of the tarantula Citharischius crawshayi (now Pelinobius muticus). Cc1a is 67% identical to the spider toxin ω-TRTX-Hg1a, an inhibitor of CaV2.3 channels. We assembled Cc1a using a combination of Boc solid-phase peptide synthesis and native chemical ligation. Oxidative folding yielded two stable, slowly interconverting isomers. Cc1a preferentially inhibited Ba2+ currents (IBa) mediated by L-type (CaV1.2 and CaV1.3) CaV channels heterologously expressed in Xenopus oocytes, with half-maximal inhibitory concentration (IC50) values of 825 nM and 2.24 μM, respectively. In rat dorsal root ganglion neurons, Cc1a inhibited IBa mediated by high voltage-activated CaV channels but did not affect low voltage-activated T-type CaV channels. Cc1a exhibited weak activity at NaV1.5 and NaV1.7 voltage-gated sodium (NaV) channels stably expressed in mammalian HEK or CHO cells, respectively. Experiments with modified Cc1a peptides, truncated at the N-terminus (ΔG1–E5) or C-terminus (ΔW35–V39), demonstrated that the N- and C-termini are important for voltage-gated ion channel modulation. We conclude that Cc1a represents a novel pharmacological tool for probing the structure and function of L-type CaV channels. 相似文献
4.
Bridget D. Mathison Lindsey L. Kimble Kerrie L. Kaspar Christina Khoo Boon P. Chew 《Nutrition Research》2014
Consumption of polyphenol-rich foods is associated with lower risk from many chronic diseases. We hypothesized that a single dose of cranberry beverage would improve indices of oxidative stress, inflammation, and urinary antibacterial adhesion activity in healthy humans. Six males and 6 females (18-35 years; body mass index, 19-25 kg/m2) consumed placebo, cranberry leaf extract beverage, or low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind, placebo-controlled cross-over experimental design trial. The washout period between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours postintervention to assess antibacterial adhesion activity. Consumption of cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase activity, whereas LCJC consumption increased (P < .05) glutathione concentrations and superoxide dismutase activity compared with placebo. Cranberry leaf extract beverage and LCJC consumption had no effect on the inflammatory biomarkers measured as compared with placebo. At 0 to 3 hours postconsumption, urine from participants who consumed cranberry beverages had higher (P < .05) ex vivo antiadhesion activity against P-fimbriated Escherichia coli compared with placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant status and inhibition of bacterial adhesion in urine. 相似文献
5.
Mitochondria play a central role in the production of reactive oxygen species as byproducts of metabolism and energy production. In order to protect cellular structures from oxidative stress-induced damage, cells have evolved elegant mechanisms for mitochondrial ROS detoxification. The mitochondrial sirtuin, SIRT3, is emerging as a pivotal regulator of oxidative stress by deacetylation of substrates involved in both ROS production and detoxification. This review will summarize recent findings on the regulation of mitochondrial ROS homeostasis by SIRT3. 相似文献
6.
Yuan Qin Xiaohua Wu Wen Huang Guohua GongDan Li Yang HeYinlan Zhao 《Journal of ethnopharmacology》2009
Ethnopharmacological relevance
Steroidal saponins from Dioscorea zingiberensis are widely used in China for curing cardiovascular diseases. However, there was little toxicological information available on them.Aim of the study
The study evaluated potential toxicity of the steroidal saponins and analyzed the metabolites in rats.Materials and methods
For the acute study, the steroidal saponins were administered to kunming mice in single doses of 112.5–9000 mg/kg given by gavage. General behavior adverse effects, mortality and liver histopathological changes were examined. For the sub-chronic toxicity study, Sprague–Dawley rats were gavaged at doses of 127.5, 255 and 510 mg/kg/day for 30 days, then examined the biochemical and hematological parameters. Metabolites in serum were analyzed by HPLC–MS.Results
The steroidal saponins caused dose-dependent general behavior adverse effects, mortality and liver histopathological changes in the acute toxicity study. In the sub-chronic toxicity study, 510 mg/kg/day of steroidal saponins increased total bilirubin (TBIL) in serum and decreased protein content in liver significantly. The metabolic process of TBIL in liver includes TBIL intaking, conjugated bilirubin forming, conjugated bilirubin excreting to biliary passage. Treatment with high dose of the steroidal saponins in vivo may lead to vacuolization of the cytoplasm of hepatocytes and canalicular cholestasis. In all doses used in the experiment, the steroidal saponins decreased aspartate aminotransferase (GOT), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) in serum and increased reduced glutathione hormone (GSH), glutathione reductase (GR) and glutathione S-transferases (GST) in liver. Diosgenin was the main metabolite in serum.Conclusions
The steroidal saponins did not show any sign of toxicity up to oral dose of 562.5 mg/kg in mice. No significant changes of biochemical and hematological parameters in rats (except at 510 mg/kg/day), it was concluded that the steroidal saponins did not appear to have significant toxicity in their traditional uses. 相似文献7.
Lash LH Putt DA Hueni SE Cao W Xu F Kulidjian SJ Horwitz JP 《Biochemical pharmacology》2002,64(10):1533-1546
Cellular energetics and redox status were evaluated in NRK-52E cells, a stable cell line derived from rat proximal tubules. To assess toxicological implications of these properties, susceptibility to apoptosis induced by S-(1,2-dichlorovinyl)-L-cysteine (DCVC), a well-known mitochondrial and renal cytotoxicant, was studied. Cells exhibited high activities of several glutathione (GSH)-dependent enzymes, including gamma-glutamylcysteine synthetase, GSH peroxidase, glutathione disulfide reductase, and GSH S-transferase, but very low activities of gamma-glutamyltransferase and alkaline phosphatase, consistent with a low content of brush-border microvilli. Uptake and total cellular accumulation of [14C]alpha-methylglucose was significantly higher when cells were exposed at the basolateral as compared to the brush-border membrane. Similarly, uptake of GSH was nearly 2-fold higher across the basolateral than the brush-border membrane. High activities of (Na(+)+K(+))-ATPase and malic dehydrogenase, but low activities of other mitochondrial enzymes, respiration, and transport of GSH and dicarboxylates into mitochondria were observed. Examination of mitochondrial density by confocal microscopy, using a fluorescent marker (MitoTracker Orange), indicated that NRK-52E cells contain a much lower content of mitochondria than rat renal proximal tubules in vivo. Incubation of cells with DCVC caused time- and concentration-dependent ATP depletion that was largely dependent on transport and bioactivation, as observed in the rat, on induction of apoptosis, and on morphological damage. Comparison with primary cultures of rat and human proximal tubular cells suggests that the NRK-52E cells are modestly less sensitive to DCVC. In most respects, however, NRK-52E cells exhibited functions similar to those of the rat renal proximal tubule in vivo. 相似文献
8.
H2O2对HL-60细胞DNA中8-羟基鸟嘌呤含量影响的研究 总被引:2,自引:0,他引:2
目的与方法:本文采用气相色谱/氢火焰离子检测器(GC/FID)和气相色谱-质谱仪选择性离子检测器(CGC/MS-SIM)探讨H2O2致HL-60细胞氧化损伤时DNA中氧化修饰碱基8-羟基鸟嘌呤(8-oh-G)含量的变化,观察HL-60细胞脂质过氧化程度和细胞内还原型谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)比值的变化。结果:结果显示H2O2可使HL-60细胞丙二醛(MDA)含量增高(P〈0.01 相似文献
9.
3-Butene-1,2-diol (BDD), an allylic alcohol and major metabolite of 1,3-butadiene, has previously been shown to cause hepatotoxicity and hypoglycemia in male Sprague-Dawley rats, but the mechanisms of toxicity were unclear. In this study, rats were administered BDD (250 mg/kg) or saline, ip, and serum insulin levels, hepatic lactate levels, and hepatic cellular and mitochondrial GSH, GSSG, ATP, and ADP levels were measured 1 or 4 h after treatment. The results show that serum insulin levels were not causing the hypoglycemia and that the hypoglycemia was not caused by an enhancement of the metabolism of pyruvate to lactate because hepatic lactate levels were either similar (1 h) or lower (4 h) than controls. However, both hepatic cellular and mitochondrial GSH and GSSG levels were severely depleted 1 and 4 h after treatment and the mitochondrial ATP/ADP ratio was also lowered 4 h after treatment relative to controls. Because these results suggested a role for hepatic cellular and mitochondrial GSH in BDD toxicity, additional rats were administered N-acetyl-l-cysteine (NAC; 200 mg/kg) 15 min after BDD administration. NAC treatment partially prevented depletion of hepatic cellular and mitochondrial GSH and preserved the mitochondrial ATP/ADP ratio. NAC also prevented the severe depletion of serum glucose concentration and the elevation of serum alanine aminotransferase activity after BDD treatment without affecting the plasma concentration of BDD. Thus, depletion of hepatic cellular and mitochondrial GSH followed by the decrease in the mitochondrial ATP/ADP ratio was likely contributing to the mechanisms of hepatotoxicity and hypoglycemia in the rat. 相似文献
10.
Differential response of MG132 cytotoxicity against small cell lung cancer cells to changes in cellular GSH contents 总被引:3,自引:0,他引:3
The effect of the depletion or oxidation of cellular GSH on cytotoxicity of MG132 was assessed. Viability loss and decrease in GSH contents in small cell lung cancer (SCLC) cells treated with MG132 was attenuated by caspase inhibitors (z-IETD.fmk, z-LEHD.fmk and z-DQMD.fmk). Thiol compounds (N-acetylcysteine and N-(2-mercaptopropionyl)glycine) and free radical scavengers reduced MG132-induced cell death. Antioxidants, including N-acetylcysteine, inhibited the MG132-induced nuclear damage, loss in mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c and caspase-3 activation. Depletion of GSH due to buthionine sulfoxime did not affect the cell viability loss, ROS formation and GSH depletion due to MG132 in SCLC cells. A thiol oxidant monochloramine, p-chloromercuribenzoate and N-ethylmaleiamide also did not affect cytotoxicity of MG132. The results suggest that the toxicity of MG132 on SCLC cells is mediated by activation of caspase-8, -9 and -3. Removal of free radicals and recovery of GSH contents may attenuate MG132-induced apoptotic cell death. Nevertheless, depletion or oxidation of cellular GSH may not affect toxicity of MG132. 相似文献