Free Radical Enhancer Xenobiotic is an Inducer of Cataract in Rabbit

Free radical enhancers, diquat, paraquat, plumbagin and juglone were used to study the oxy radical-induced damage to the rabbit lens in vitro and in vivo. Each compound caused a 6–8 fold increase in malondialdehyde (MDA) and a 30–55% decrease in reduced glutathione of the lens in vim. These peroxidative and oxidative changes were potentiated in the presence of 100% 0., abolished by N, and prevented by desferal-Mn (III) (DF-Mn) or liposomal superoxide dismutase (LSOD) indicating the involvement of O₂^?.

Diquat injected intravitreally as a single dose (300nmole in 30μl of isotonic saline) in the right eye of a 5-wk-old Dutch belted rabbit, induced early cataract after 24–72h. The lens of the contralateral control eye injected with isotonic saline had no change. In the right eye, O₂,^? and OH -productions were significantly (P < 0.01) higher; O₂-, was about 16 fold higher in the aqueous humor and vitreous humor, and 5 fold in the lens and retina, and OH. was 35 fold higher in the aqueous humor, 2 fold in vitreous humor and 5 fold in the lens and retina as compared to the respective tissues of the control eye. Enhanced lipid peroxidation in the lens was apparent from the higher levels of MDA and formation of aminophospholipid-MDA Schiff-base conjugates.

We propose that cyclic oxidation-reduction of xenobiotics coupled to the endogenous redox systems in the eye, could generate oxy radicals in excessive amounts, triggering cataractogcnesis.     

Calcium Ions Promote Superoxide Dismutase 1 (SOD1) Aggregation into Non-fibrillar Amyloid: A LINK TO TOXIC EFFECTS OF CALCIUM OVERLOAD IN AMYOTROPHIC LATERAL SCLEROSIS (ALS)?*

Imbalance in metal ion homeostasis is a hallmark in neurodegenerative conditions involving protein deposition, and amyotrophic lateral sclerosis (ALS) is no exception. In particular, Ca²⁺ dysregulation has been shown to correlate with superoxide dismutase-1 (SOD1) aggregation in a cellular model of ALS. Here we present evidence that SOD1 aggregation is enhanced and modulated by Ca²⁺. We show that at physiological pH, Ca²⁺ induces conformational changes that increase SOD1 β-sheet content, as probed by far UV CD and attenuated total reflectance-FTIR, and enhances SOD1 hydrophobicity, as probed by ANS fluorescence emission. Moreover, dynamic light scattering analysis showed that Ca²⁺ boosts the onset of SOD1 aggregation. In agreement, Ca²⁺ decreases SOD1 critical concentration and nucleation time during aggregation kinetics, as evidenced by thioflavin T fluorescence emission. Attenuated total reflectance FTIR analysis showed that Ca²⁺ induced aggregates consisting preferentially of antiparallel β-sheets, thus suggesting a modulation effect on the aggregation pathway. Transmission electron microscopy and analysis with conformational anti-fibril and anti-oligomer antibodies showed that oligomers and amyloidogenic aggregates constitute the prevalent morphology of Ca²⁺-induced aggregates, thus indicating that Ca²⁺ diverts SOD1 aggregation from fibrils toward amorphous aggregates. Interestingly, the same heterogeneity of conformations is found in ALS-derived protein inclusions. We thus hypothesize that transient variations and dysregulation of cellular Ca²⁺ levels contribute to the formation of SOD1 aggregates in ALS patients. In this scenario, Ca²⁺ may be considered as a pathogenic effector in the formation of ALS proteinaceous inclusions.     

A novel small molecule HSP90 inhibitor,NXD30001, differentially induces heat shock proteins in nervous tissue in culture and in vivo

Heat shock proteins (HSPs) are attractive therapeutic targets for neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), characterized by aberrant formation of protein aggregates. Although motor neurons have a high threshold for activation of HSP genes, HSP90 inhibitors are effective inducers. This study evaluated NXD30001, a novel, small molecule HSP90 inhibitor based on the radicicol backbone, for its ability to induce neuronal HSPs and for efficacy in an experimental model of ALS based on mutations in superoxide-dismutase 1 (SOD1). In motor neurons of dissociated murine spinal cord cultures, NXD30001-induced expression of HSP70/HSPA1 (iHSP70) and its co-chaperone HSP40/DNAJ through activation of HSF1 and exhibited a protective profile against SOD1^G93A similar to geldanamycin, but with less toxicity. Treatment prevented protein aggregation, mitochondrial fragmentation, and motor neuron death, important features of mutant SOD1 toxicity, but did not effectively prevent aberrant intracellular Ca²⁺ accumulation. NXD30001 distributed to brain and spinal cord of wild-type and SOD1^G93A transgenic mice following intraperitoneal injection; however, unlike in culture, in vivo levels of SOD1 were not reduced. NXD30001-induced expression of iHSP70 in skeletal and cardiac muscle and, to a lesser extent, in kidney, but not in liver, spinal cord, or brain, with either single or repeated administration. NXD30001 is a very useful experimental tool in culture, but these data point to the complex nature of HSP gene regulation in vivo and the necessity for early evaluation of the efficacy of novel HSP inducers in target tissues in vivo.     

The Clinical and Laboratory Studies of Superoxide Dismutase Activity in the Human Whole Blood with Early Gastric Cancer

In this study, we tried to evaluate the usefulness of Superoxide Dismutase (SOD) activity in detecting gastric cancer. SOD was determined according to M. Minami and H. Yoshikawa. a simple and inexpensive assay method. For II fibrognstroscopy and pathological proved gastric cancer cases, the average levels of SOD activity was found significantly lower than 30 patients with gastric diseases, 8 patients with atypical hyperplasia and 32 controls.     

Synthesis,characterization and biological aspects of novel five-coordinated dimeric-Cu(II) systems

The structural and spectroscopic properties of novel five-coordinated dimeric-Cu(II) system have been investigated. The biocidal activities of all eight compounds, ligands, cupric nitrate and standard drugs against six bacteria and three fungi were determined. The DNA interaction activity of complexes was studied using spectrophotometry and electrophoresis. The superoxide dismutase (SOD)-like activity of the complexes was compared with previously reported monomeric- and dimeric copper complexes. The results support the five-coordinated dimeric square pyramidal geometry for the quinolone-Cu(II) system.     

妊娠期糖尿病患者氧化应激水平变化及临床意义*

目的:研究GDM孕妇与正常孕妇血清MDA、SOD及GSH水平变化,探索它们与GDM之间的相互关系,追踪各组妊娠结局研究其临床意义。方法:选取175例孕妇为研究对象,分为GDM组(93例)和对照组(82例)。采用微量法测定血清丙二醛(MDA)、谷胱甘肽(GSH)及超氧化物歧化酶(SOD)水平,并对妊娠结局进行相关性分析。结果:(1) GDM组年龄、孕前体重、BMI值均高于对照组,GSH和SOD水平均低于对照组,MDA水平高于对照组,差异有统计学意义(P0.05);(2) GDM组MDA水平与孕前体重呈负相关(r=-0.3547,P0.05),SOD水平与新生儿出生体重呈正相关(r=0.3292,P0.05),SOD值与早产之间有密切联系(足月产12.68±0.85 vs.早产8.08±1.18, P 0.05),GSH、SOD水平与孕前体重之间,MDA、GSH水平与新生儿出生体重之间,MDA、GSH水平与早产之间均无明显相关性(P0.05),MDA、GSH和SOD水平与剖宫产及胎膜早破均无明显相关性(P0.05)。结论:GDM存在明显的氧化应激反应,GSH、MDA与SOD可以作为评估GDM氧化应激的有效标志物,其与不良妊娠结局有关。     

rh-BNP联合阿托伐他汀治疗急性心梗后心衰的临床疗效及对患者血清cTn-I、Myo、CK-MB水平的影响

目的:研究重组人脑利钠肽(rh-BNP)联合阿托伐他汀治疗急性心梗后心衰的临床效果及对患者血清心肌肌钙蛋白(cardiac troponin,cTn-I)、肌红蛋白(Myoglobin,Myo)、肌酸激酶同工酶(CK-MB)水平的影响。方法:选择我院2017年2月～2019年1月收治的72例急性心梗后心衰患者,按随机数字表法分为观察组38例,对照组34例。对照组给予阿托伐他汀治疗,观察组在对照组基础上另加rh-BNP,观察和比较两组的临床疗效,治疗前后血清cTn-I、Myo、CK-MB水平的变化及治疗后不良反应的发生情况。结果:治疗后,观察组总有效率明显高于对照组(P0.05),血清cTn-I、Myo、CK-MB水平均显著低于对照组[(0.23±0.10) vs.(0.16±0.08)、(27.54±3.86) vs.(21.62±2.54)、(70.82±9.25) vs.(61.28±8.33)](P0.05)。观察组治疗后不良反情况总发生率为7.89%,明显低于对照组(26.47%,P0.05)。结论:与单用阿托伐他汀治疗相比,静脉注射rh-BNP联合阿托伐他汀治疗急性心梗后心衰可显著提高临床疗效和安全性,有效减低血清cTn-I、Myo、CK-MB水平。     

Subcellular cadmium distribution and antioxidant enzymatic activities in the leaves of four Hylotelephium spectabile populations exhibit differences in phytoextraction potential

Hylotelephium spectabile with high tolerance to cadmium (Cd) might be a potential candidate for phytoremediation. However, the mechanisms for Cd accumulation and tolerance in H. spectabile are poorly understood. Four H. spectabile populations, namely HB1, HB2, JS, and LN, were selected to investigate their Cd extraction potential and the underlying mechanism of Cd accumulation, focusing on subcellular distribution and antioxidant enzymes. The Cd concentration, bioconcentration factor and transfer factor of the LN was significantly higher than other populations, particularly with increasing Cd exposure, and no obvious growth inhibition observed. Segregation of excessive Cd to Cd-rich granule in LN was much higher than other populations which reveal one possible mechanism of Cd accumulation. A significant increase in superoxide dismutase (SOD) and catalase (CAT) activities with increasing Cd stress suggested SOD and CAT contribute to the Cd tolerance of H. spectabile. LN displayed significantly higher and constant peroxidase (POD) activities than other populations, which indicated that an effective mechanism existed in the LN to cope with Cd stress. Therefore, the subcellular distribution and antioxidant enzymes might play important roles in Cd accumulation and tolerance of H. spectabile. LN possessed high Cd extraction potential, and further studies under field conditions are warranted.