Evaluation of biomarkers of oxidative stress and antioxidant capacity in the cord blood of preterm low birth weight neonates

Objective: The objective of the study is to investigate the association between oxidative stress markers and enzymatic / non-enzymatic antioxidants (marker of the resistance in body to oxidative damage) in the cord blood of preterm low birth weight (LBW) neonates. Methods: Malondialdehyde (MDA), carbonyl proteins, total antioxidant capacity and Vitamin A, E and C levels in the cord blood were determined by spectrophotometry. Results: Increased lipid peroxidation, protein oxidation with decreased values of vitamin A, E, C and total antioxidant capacity were observed in the preterm LBW newborns. Observations of negative correlation between MDA and protein carbonyl with antioxidants vitamin A, E and C and total antioxidant status points towards the existence of oxidative stress in the preterm LBW newborns. Conclusions: Poor fetal growth affects the development of antioxidant defenses of preterm LBW babies, predisposing them to higher oxidative stress, which in turn may partly account for increased morbidity and mortality in these infants. The presence of an association between oxidative stress biomarkers and enzymatic /non-enzymatic antioxidants in the cord blood of preterm LBW neonates suggest that increased oxidative stress may be the result of changes in the levels of certain enzymatic and non-enzymatic antioxidants due to the cause or the effect of oxidative damage occurring at the molecular level.     

Ethanol withdrawal acts as an age-specific stressor to activate cerebellar P38 kinase

We investigated whether protein kinase P38 plays a role in the brain-aging changes associated with repeated ethanol withdrawal (EW). Ovariectomized young, middle-age and older rats, with or without 17β-estradiol (E2) implantation, received a 90-day ethanol with repeated withdrawal. They were tested for active pP38 expression in cerebellar Purkinje neurons and whole-cerebellar lysates using immunohistochemistry and enzyme-linked immunosorbent assay, respectively. They were also tested for the Rotarod task to determine the behavioral manifestation of cerebellar neuronal stress and for reactive oxygen species (ROS) and mitochondrial protein carbonyls to determine oxidative mechanisms. Middle-age EW rats showed higher levels of pP38-positive Purkinje neurons/cerebellar lysates, which coincided with increased mitochondrial protein oxidation than other diet/age groups. Exacerbated motor deficit due to age–EW combination also began at the middle-age. In comparison, ROS contents peaked in older EW rats. E2 treatment mitigated each of the EW effects to a different extent. Collectively, pP38 may mediate the brain-aging changes associated with pro-oxidant EW at vulnerable ages and in vulnerable neurons in a manner protected by estrogen.     

Apoptotic role of natural isothiocyanate from broccoli (Brassica oleracea italica) in experimental chemical lung carcinogenesis

Abstract

Context: Sulforaphane (SFN) [1-isothiocyanato-4-(methylsulfinyl)butane] is a naturally occurring isothiocyanate found in cruciferous vegetables such as broccoli [Brassica oleracea L. var. italica Plenck. (Brassicaceae)]. Since it is among the most potent bioactive components with antioxidant and antitumor properties, it has received intense attention in the recent years for its chemopreventive properties.

Objective: The present work determined the rehabilitating role in alleviating the oxidative damage caused by benzo(a)pyrene [B(a)P] to biomolecules and the apoptotic cascade mediated by orally administered isothiocyanate-SFN (9?µmol/mouse/day) against B(a)P (100?mg/kg body weight, i.p.) induced pulmonary carcinogenesis in Swiss albino mice.

Materials and methods: Oxidative damage was assessed by measuring lipid peroxidation, 8-hydroxydeoxyguanosine, hydrogen peroxide (H₂O₂) production, glycoprotein components, protein carbonyl levels and DNA-protein crosslinks. DNA fragmentation by agarose gel electrophoresis and caspase-3 activity by ELISA proved apoptotic induction by SFN along with the protein expression of Bcl-2, Bax and Cyt c.

Results: SFN treatment was found to decrease the H₂O₂ production (p?<?0.001) in cancer induced animals, proving its antioxidant potential. Apoptosis was induced by increasing the release of Cyt c (p?<?0.001) from mitochondria, decreasing and increasing the expression of Bcl-2 (p?<?0.01) and Bax (p?<?0.001), respectively. Caspase-3 activity was also enhanced (p?<?0.001) which leads to DNA fragmentation in SFN treated groups.

Conclusion: Our results reflect the rehabilitating role of SFN in B(a)P induced lung carcinogenesis.     

糖尿病与唾液中DNA、蛋白质和脂类氧化损伤

目的：观察糖尿病是否与唾液中氧化还原动态平衡的改变相关。方法：用ELISA方法分析148名糖尿病患者和475名对照的非刺激性唾液中氧胁迫损伤标志物8-羟基-2′-脱氧鸟苷（8-hydmxy-2′-deoxyguanosine,8-OHdG）、堡白质羰基（Protein carbonyls,PC）和8-异前列腺素F2α（8-epi—prostaglandin—F2α,8-epi—PGF2α）的含量。用逻辑相关分析的统计学方法分析氧胁迫损伤指标与使用胰岛素、二甲双胍和餐饮控制糖尿病患者之间的相关性。结果：（i）与对照组相比糖尿病组唾液中的Log8-OHdG、Log PC和Log 8-epi—PGF2α明显升高;（ii）Ⅰ型糖尿病组唾液中的Log PC明显较对照组高,Ⅱ型糖尿病组Log 8-OHdG、Log PC和Log 8-epi—PGF2α均较对照组有明显升高;（iii）二甲双胍治疗组和单纯餐饮控制的糖尿病组唾液Log 8-OHdG和Log PC水平较高;（iv）单纯胰岛素治疗组和胰岛素及二甲双胍联合治疗组唾液Log PC水平高于对照组;（v）多变量分析和条件逻辑回归分析表明Log 8-OHdG、Log PC、Log8-epi—PGF2α和糖尿病间存在明显的相关性。结论：糖尿病患者唾液中氧化性DNA、脂类和蛋白质损伤产物8-OHdG、8-epi—PGF2α、PC水平均明显升高,表明存在唾液中的氧化还原动态平衡紊乱。唾液氧胁迫指标的分析有可能成为一种新的疾病监测方式,并且提示一种疾病干预的新途径。     

Novel [FeFe]-Hydrogenase Mimics: Unexpected Course of the Reaction of Ferrocenyl α-Thienyl Thioketone with Fe3(CO)12

The influence of the substitution pattern in ferrocenyl α-thienyl thioketone used as a proligand in complexation reactions with Fe₃(CO)₁₂ was investigated. As a result, two new sulfur–iron complexes, considered [FeFe]-hydrogenase mimics, were obtained and characterized by spectroscopic techniques (¹H, ¹³C{¹H} NMR, IR, MS), as well as by elemental analysis and X-ray single crystal diffraction methods. The electrochemical properties of both complexes were studied and compared using cyclic voltammetry in the absence and in presence of acetic acid as a proton source. The performed measurements demonstrated that both complexes can catalyze the reduction of protons to molecular hydrogen H₂. Moreover, the obtained results showed that the presence of the ferrocene moiety at the backbone of the linker of both complexes improved the stability of the reduced species.     

Comparison of Five Oxidative Stress Biomarkers in Vegans and Omnivores from Germany and Finland

When the amount of reactive oxygen species produced by human metabolism cannot be balanced by antioxidants, this phenomenon is commonly referred to as oxidative stress. It is hypothesised that diets with high amounts of plant food products may have a beneficial impact on oxidative stress status. However, few studies have examined whether a vegan diet is associated with lower oxidative stress compared to an omnivorous diet. The present cross-sectional study aimed to compare the levels of five oxidative stress biomarkers in vegans and omnivores. Data of 36 vegans and 36 omnivores from Germany and of 21 vegans and 18 omnivores from Finland were analysed. HPLC coupled with mass spectrometry or fluorescence detection and ELISA methods were used to measure the oxidative stress biomarkers malondialdehyde (MDA), protein carbonyls and 3-nitrotyrosine in plasma and 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in 24 h urine. Analyses of variance and covariance, considering potential confounders, were used. Vegans and omnivores showed no differences in MDA and protein carbonyl concentrations. In Finnish but not in German vegans, the concentrations of 3-nitrotyrosine were lower compared to those in omnivores (p = 0.047). In Germany, vegans showed lower excretion levels of 8-iso-PGF2α than omnivores (p = 0.002) and with a trend also of 8-OHdG (p = 0.05). The sensitivity analysis suggests lower 8-iso-PGF2α excretion levels in women compared to men, independently of the dietary group. The present study contributes to expanding our knowledge of the relationship between diet and oxidative stress and showed that 3-nitrotyrosine, 8-OHdG and 8-iso-PGF2α tended to be lower in vegans. Furthermore, studies are recommended to validate the present findings.     

Lead modification via computational studies: Synthesis of pyrazole-containing β-amino carbonyls for the treatment of type 2 diabetes

This article describes studies on the design, synthesis, and biological evaluation of pyrazole-containing β-amino carbonyl compounds ( 5a – 5q ) as DPP-4 inhibitors and anti-diabetic agents. In contrast, mannich reactions went smoothly with bismuth nitrate (Bi (NO₃)₃) catalyst in the presence of ethanol and produced pyrazole-containing β-amino carbonyl compounds in good yield. Molecular docking studies of designed derivatives with DPP-4 enzyme (PDB: 2OLE), compounds 5d , 5h , 5j , and 5k showed excellent interaction. 3D QSAR and pharmacophoric model studies were also carried out. ADMET parameters, pharmacokinetic properties, and in vivo toxicity studies further confirmed that all the designed compounds were found to have good bioavailability and were less toxic. Further, these compounds were evaluated as enzyme-based in vitro DPP-4 inhibitory activity, and 5d , 5h , 5i , 5j , and 5k exhibited IC₅₀ toward DPP-4 enzyme of 10.52, 10.41, 5.55, 4.16, and 7.5 nM, respectively. The most potent compound, 5j , was further selected for in vivo anti-diabetic activity using an STZ-induced diabetic mice model, and 5j showed a significant diabetic control effect.