Effects of di(2‐ethylhexyl)phthalate on testicular oxidant/antioxidant status in selenium‐deficient and selenium‐supplemented rats

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.     

五味子酚对氧自由基引起大鼠脑突触体和线粒体损伤的保护作用

以Fe²⁺-半胱氨酸(Cys)为氧自由基生成系统,在体外模仿脑出血或脑外伤引起的氧自由基损伤的模型,观察五味子酚是否对Fe²⁺-Cys引起的大鼠脑突触体和线粒体损伤有保护作用,以探讨Sal用于延缓衰老、防治某些神经系统疾病的可能性。结果显示,与Fe²⁺-Cys共温孵可使脑突触体和线粒体MDA生成量显著增加,线粒体ATPase活性下降。而预先加入Sal(10^{-6mol·L-1)可抑制MDA生成,防止线粒体ATPase活性降低。Sal对Fe2+-Cys引起的线粒体肿胀和膜流动性降低也有明显的保护作用,并能防止Fe2+-Cys所致线粒体和突触体形态的病理性损伤。结果提示,Sal对氧自由基引起的大鼠脑突触体和线粒体损伤有明显保护作用。}     

睡眠呼吸暂停患者肋间外肌氧化应激的研究

目的 探索睡眠呼吸暂停(OSAS)患者的肋间外肌是否存在氧化应激及其可能的进一步损害.方法 按照特定的标准经过测试确定16例OSAS患者,采用免疫印迹等方法测定其肋间外肌还原型谷胱甘肽(GSH)、蛋白质羰基化以及丙二醛一蛋白质加合物,并与16例非OSAS受试者进行比较.结果 OSAS患者的用力呼气容积(FEV)、用力肺活量(FVC)、睡眠最低血氧饱和度(LSaO2)和最大通气量(MVV)明显低于非OSAS对照组(P＜0.001或0.05);睡眠呼吸暂停低通气指数(AHI)和功能残气量(FRC)则明显高于对照组(P＜0.001或P＜0.05).OSAS患者肋间外肌的还原型谷胱甘肽明显降低(P＜0.001),蛋白质羰基化水平和丙二醛(MDA)-蛋白加合物明显上升(P＜0.001或P＜0.05).结论 OSAS患者肋间外肌氧化应激水平升高,并伴有蛋白质氧化应激损伤.     

GSH对砷氧化损伤保护作用的研究

[目的]研究细胞内谷胱甘肽（GSH）对砷致人角质形成细胞系（HacaT）氧化损伤的保护作用。[方法]用流式细胞仪检测细胞内二氯荧光素（DCF）的荧光强度;用改良硫代巴比妥酸荧光法测定细胞内丙二醛（MDA）含量。[结果]单独用NaAsO2作用后,DCF荧光强度和MDA含量与对照组比较差异有显著性意义（P〈0．05）,用N-乙酰半胱氨酸（NAC）预处理后,细胞内DCF荧光强度和MDA含量与砷作用组相比差异有显著性意义（P〈0．05）,其中MDA达到对照组水平。用丁硫氨酸亚矾胺（BSO）预处理细胞后,DCF荧光强度和MDA含量与NaAsO2单独作用组相比明显增高（P〈0．05）。[结论]NAC可减轻砷对细胞的氧化损伤,而BSO则可加重其氧化损伤,说明细胞内的GSH可对砷引起的氧化损伤起一定的保护作用。     

Glutathione and its metabolizing enzymes in patients with different benign and malignant diseases

Objectives: Evaluation of glutathione (GSH) system in different tumors to reveal its potential usefulness in a clinical setting.

Design and methods: In addition to 10 normal controls, blood and tissue samples (85 benign and 109 malignant) from patients with breast, ovarian, prostatic, and liver neoplasms were investigated. The GSH concentration, glutathione S-transferase, glutathione peroxidase, and glutathione reductase activities were biochemically measured.

Results: Whereas all the components of the GSH system increased in patients with breast tumors, few components were significantly changed in patients with malignant ovarian, prostatic as well as metastatic liver diseases. GSH had the highest Z scores in ovarian and breast tumors. It was correlated (p < 0.05) with both glutathione S-transferase, glutathione peroxidase in breast cancer and with glutathione S-transferase only in prostate cancer. No correlation could be found in the expression of the GSH system in the blood and tissues of the same group of patients.

Conclusion: This work revealed that measurement of some and/or all components of the GSH system might be of clinical value in some malignant cases.     

参芪地黄汤通过GPX4信号通路调控糖尿病肾病小鼠铁死亡的机制研究

[目的]研究参芪地黄汤对糖尿病肾病（diabetic nephropathy,DN）模型小鼠的治疗效果及调控谷胱甘肽过氧化物酶4(glutathione peroxidase 4, GPX4)信号通路对铁死亡的影响。[方法]通过链脲佐菌素（streptozotocin,STZ）联合高脂饮食诱导建立DN小鼠模型,并灌胃不同剂量的参芪地黄汤。通过检测各组小鼠体质量、血糖、肌酐（creatinine,Cr）、尿素氮（blood urea nitrogen,BUN）、24 h尿蛋白,肾石蜡切片苏木精-伊红（hematoxylin-eosin,HE）染色及过碘酸-雪夫（periodic acid-Schiff,PAS）染色评估参芪地黄汤对DN模型小鼠的治疗作用;通过检测丙二醛（malondialdehyde,MDA）、活性氧（reactive oxygen species,ROS）、4-羟基壬烯醛（4-hydroxynonenal,4-HNE）水平,评估参芪地黄汤对DN模型小鼠脂质过氧化水平的影响;通过检测总Fe水平以及转铁蛋白（transferin）、前列腺6跨膜上皮抗原3(six-trans...     

Anti-glycative and anti-inflammatory effects of protocatechuic acid in brain of mice treated by d-galactose

Protocatechuic acid (PCA) at 0.5%, 1% or 2% was supplied to d-galactose (DG) treated mice for 8 week. PCA intake at 2% increased its deposit in brain. DG treatment increased brain level of reactive oxygen species, protein carbonyl, carboxymethyllysine, pentosidine, sorbitol, fructose and methylglyoxal (P < 0.05). PCA intake, at 1% and 2%, lowered brain level of these parameters (P < 0.05). DG treatments enhanced activity and protein expression of aldose reductase (AR) and sorbitol dehydrogenase, as well as declined glyoxalase I (GLI) activity and protein expression (P < 0.05). PCA intake at 1% and 2% reduced activity and protein expression of AR (P < 0.05), and at 2% restored GLI activity and expression (P < 0.05). DG injection also elevated cyclooxygenase (COX)-2 activity and expression, and increased the release of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and prostaglandin E₂ in brain (P < 0.05). PCA intake decreased these cytokines (P < 0.05), and at 1% and 2% suppressed COX-2 activity and expression (P < 0.05). PCA intake at 1% and 2% also lowered DG-induced elevation in activity, mRNA expression and protein production of nuclear factor kappa B p65 (P < 0.05). These findings suggest that the supplement of protocatechuic acid might be helpful for the prevention or alleviation of aging.     

Sensitivity and specificity of human brain glutathione concentrations measured using short‐TE 1H MRS at 7 T

Although the MR editing techniques that have traditionally been used for the measurement of glutathione (GSH) concentrations in vivo address the problem of spectral overlap, they suffer detriments associated with inherently long TEs. The purpose of this study was to characterize the sensitivity and specificity for the quantification of GSH concentrations without editing at short TE. The approach was to measure synthetically generated changes in GSH concentrations from in vivo stimulated echo acquisition mode (STEAM) spectra after in vitro GSH spectra had been added to or subtracted from them. Spectra from five test subjects were synthetically altered to mimic changes in the GSH signal. To account for different background noise between measurements, retest spectra (from the same individuals as used to generate the altered data) and spectra from five other individuals were compared with the synthetically altered spectra to investigate the reliability of the quantification of GSH concentration. Using STEAM spectroscopy at 7 T, GSH concentration differences on the order of 20% were detected between test and retest studies, as well as between differing populations in a small sample (n = 5) with high accuracy (R² > 0.99) and certainty (p ≤ 0.01). Both increases and decreases in GSH concentration were reliably quantified with small impact on the quantification of ascorbate and γ‐aminobutyric acid. These results show the feasibility of using short‐TE ¹H MRS to measure biologically relevant changes and differences in human brain GSH concentration. Although these outcomes are specific to the experimental approach used and the spectral quality achieved, this study serves as a template for the analogous scrutiny of quantification reliability for other compounds, methodologies and spectral qualities. Copyright © 2016 John Wiley & Sons, Ltd.     

Expression of muscarinic acetylcholine receptors in hepatocytes from rat fibrotic liver

The pathological changes of parasympathetic nerve are considered as an independent prognostic factor of the survival rate of patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes and hepatic stellate cells, but the subtypes of mAchR expressions in HCs are still uncertain. Here, we investigate the expression of mAchR in hepatic fibrosis on rats. 3 ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis on rats and the hepatocytes were isolated. Compared to the normal state, the expression levels of m1, 3, 5 in fibrotic liver tissues or hepatocytes were obviously increased, while m2, 4 decreased. 10 μM pilocarpine or 10 μM acetylcholine could increase the alanine aminotransferase (ALT), hydroxyproline (Hyp), collagen I, III in the hepatocytes, and decreased albumin (ALB). They also changed the expressions of mAchR similarly as the fibrotic hepatocytes and livers. However, atropine could ameliorate the state of fibrotic hepatocytes. These data indicate that mAchR played an important role in the regulation of hepatic fibrosis process. Targeting mAchR would have therapeutic potential for hepatic fibrosis.