Effect of two monoterpene phenols on antioxidant defense system in Candida albicans

Thymol and carvacrol from the class of monoterpene phenols are one of the most potent plant essential oil components possessing antimicrobial effects. Known for their wide bioactive spectrum, these positional isomers of isopropyl cresol deplete ergosterol content, compromise membrane permeability, block efflux pumps and restore antifungal susceptibility to fluconazole in resistant Candida strains. Exposure to these natural compounds induces a cascade of stress responses, which are important to comprehend their microbicidal mechanisms. This study evaluates the antioxidant defense response to lower concentrations of thymol and carvacrol in Candida albicans. The antioxidant defense responses in C. albicans are important for developmental mechanisms pertaining to resistance against the immune system, infection establishment and drug resistance. In this view, primary and secondary antioxidant defense enzymes, and oxidative stress markers including glutathione and lipid peroxidation were determined in C. albicans cells exposed to lower concentrations of thymol and carvacrol. These compounds were found to induce oxidative stress and compromised the antioxidant defense system in C. albicans at lower concentrations. This study helps in understanding the ‘in cell’ antifungal mechanisms of natural monoterpene phenols originating from oxidative stress. Thymol and carvacrol induced membrane deterioration reported earlier, is further explained as a result of a toxic radical cascade mediated by lipid peroxidation. Findings reinforce the observed toxic oxidizing effects of these compounds as a consequence of direct damage to antioxidant components and not to their genetic manipulations.     

L-精氨酸对高糖引起内皮功能失调的保护作用

目的通过研究L-精氨酸和N^G-硝基-L-精氨酸-甲基酯对人脐静脉内皮细胞产生一氧化氮和超氧阴离子的影响以探讨L-精氨酸对高糖引起内皮功能失调的保护作用。方法不同浓度L-精氨酸、N^G-硝基-L精氨酸-甲基酯、葡萄糖和胰岛素加入体外培养的人脐静脉内皮细胞，24h后分别测定细胞培养液中一氧化氮舍酶和超氧化物歧化酶活性及一氧化氮和超氧阴离子浓度。结果25mmol／L葡萄糖使内皮细胞一氧化氮合酶活性增高，一氧化氮产生增加，超氧化物歧化酶活性下降，超氧阴离子产生增加；L-精氨酸对一氧化氮舍酶、一氧化氮、超氧化物歧化酶的影响与对照组相比无显著性差异（P〉0．05）。但可以使超氧阴离子产生减少；25mmol／L葡萄糖＋L-广精氨酸使内皮细胞一氧化氮舍酶活性增强，一氧化氮产生增加，L-精氨酸可以改善高糖引起的超氧阴离子升高。不同浓度的胰岛素使内皮细胞一氧化氮合酶活性增高，一氧化氮产生增加，对超氧化物歧化酶活性和超氧阴离子产生无明显影响；不同浓度胰岛素＋L-精氨酸使内皮细胞一氧化氮合酶活性增强，一氧化氮产生增加，对超氧化物歧化酶活性无明显影响，但可以使超氧阴离子水平降低。100μmol／LN^G-硝基-L-广精氨酸-甲基酯使内皮细胞一氧化氮合酶活性下降，一氧化氮产生减少，对超氧化物歧化酶活性无明显影响，但使超氧阴离子产生增加；25mmol／L葡萄糖＋N^G-硝基-L-精氨酸-甲基酯使内皮细胞一氧化氮合酶活性下降，一氧化氮产生减少，但对高糖引起的超氧化物歧化酶活性下降和超氧阴离子升高无明显影响。10mu胰岛素＋10μmol／L N^G-硝基-L-精氨酸．甲基酯和100mu胰岛素＋100μmol／L N^G-硝基-L-精氨酸-甲基酯使内皮细胞一氧化氮合酶活性下降，一氧化氮产生减少，对超氧化物歧化酶活性无明显影响，但使超氧阴离子升高。结论L-精氨酸对一氧化氮合酶、一氧化氮、超氧化物歧化酶无明显影响，但可以使超氧阴离子产生减少；N^G-硝基-L-精氨酸-甲基酯使内皮细胞一氧化氮合酶活性下降。一氧化氮产生减少，对超氧化物歧化酶活性无明显影响，但使超氧阴离子产生增加。     

病毒性肝炎患者血浆LPO,VitE及红细胞SOD水平与肝功能的关系

检测45例病毒性肝炎患者血浆LPO,VitE及红细胞SOD水平,发现急性肝炎组、慢活肝组、重症肝炎组及肝硬化组血浆LPO值分别为5.52±2.6、9.67±5.11、18.22±6.81和7.51±5.051mmol/L.均明显高于正常对照组2.77±0.67(P<0.05),重症肝炎组升高最明显。血浆VitE值分别为9.22±3.83、7.81±2.67、6.56±2.64和6.99±2.67μmol/L,均明显低于正常对照组13.95±4.80(P<0.001),重症肝炎组下降最明显。4种肝病红细胞SOD水平与正常对照组比较无明显改变(P>0.05)。LPO增多、VitE减少与肝功能损伤程度一致。     

Effect of some free radical scavengers on reperfusion induced arrhythmias in the isolated rat heart

The possible role of oxygen free radicals in the development of reperfusion arrhythmias was investigated using a 10-min period of coronary ligation followed by reperfusion in the isolated rat heart. Superoxide dismutase (5 to 20 u/ml) glutathione (10(-5) to 10(3)M) and ascorbic acid (10(-4) to 5 X 10(-4) M) when given before coronary ligation attenuated the development of reperfusion arrhythmias. Mannitol (2 X 10(-2)M) and catalase (100 and 300 u/ml) did not have any significant effect on reperfusion arrhythmias when given alone but they did potentiate the antiarrhythmic effect of superoxide dismutase. Glutathione, and a combination of superoxide dismutase, catalase and mannitol also reduced the incidence of reperfusion induced ventricular fibrillation when given just before reperfusion. By perfusing hearts with ferricytochrome C it was possible to show an increased reduction of ferricytochrome C during the first minute of reperfusion which could be prevented by the addition of superoxide dismutase. These results provide evidence that oxygen free radicals are produced and may be important in the genesis of reperfusion induced arrhythmias in the isolated rat heart.     

沙棘总黄酮防紫外线损伤的实验研究

目的：通过中波紫外线（UVB）辐射皮肤损伤模型来探讨沙棘总黄酮对皮肤的保护修复作用,为寻找新型抗紫外线的药物提供实验依据。方法通过 UVB 反复照射,构建 UVB 辐射小鼠皮肤损伤模型,观察各组实验动物皮肤形态学变化、皮肤中超氧化物歧化酶（SOD）活性、皮肤内脂类受过氧化损伤的程度即丙二醛（MDA）的量和胶原蛋白量的变化程度。结果模型组较正常组皮肤形态学变化明显,表皮层增加,真皮层增厚,UVB 辐射皮肤损伤模型构建成功;模型组较正常组 SOD 活性和 MDA的量分别是极显著降低和升高（P＜0．01）,而阳性对照组和沙棘总黄酮给药组较模型组 SOD 的活性和 MDA 的量分别是极显著升高和降低（P＜0．01）;模型组较正常组胶原蛋白量显著降低（P＜0．05）,阳性对照组和沙棘总黄酮给药组胶原蛋白量较高（P＜0．01）,但阳性对照组出现了增生性瘢痕。结论沙棘总黄酮能有效防止 UVB 反复照射对皮肤造成的损伤,提高皮肤组织中SOD 活性和胶原蛋白量,抑制 MDA 的量升高和瘢痕增生,并对 UVB 导致小鼠皮肤光老化有拮抗作用。     

急性脑梗死和脑出血患者血清SOD与HCY水平分析

目的探讨血清超氧化物歧化酶(SOD)、同型半胱氨酸(HCY)检测在急性脑梗死和急性脑出血中的意义。方法选择确诊的急性脑梗死患者251例、急性脑出血患者204例、体检健康者485例,检测并比较血清SOD、HCY水平。结果急性脑梗死和急性脑出血患者血清SOD水平均低于健康者,而HCY水平则高于健康者(P0.05)。不同类型脑梗死患者血清SOD、HCY水平比较差异有统计学意义(P0.05)。结论检测急性脑梗死及急性脑出血患者血清SOD、HCY水平对判断病情、评价疗效等具有重要意义。     

17β雌二醇对大鼠创伤性脑损伤的保护作用

目的 探讨大鼠创伤性脑损伤后17β雌二醇对脑组织的保护作用。方法 选择雄性成年 SD大鼠 45 只, 按随机数字表法分为三组, 每组15只: 对照组仅开骨窗, 不损伤脑组织;致伤组制大鼠自由落体脑撞击伤模型;处理组在致伤组的基础上, 伤前1周腹腔注射17β雌二醇溶液(1 mg/kg), 1次/d。余两组仅注射同体积的蓖麻油。在伤后 6 h、 24 h 及48 h 测量各组脑组织含水量、 丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性。结果 致伤组和处理组在伤后 6 h、24 h、48 h 三个时间点脑组织含水量均高于对照组(P<0.05)。在伤后 6 h, 致伤组和处理组脑组织含水量比较差异无统计学意义[(58.39±0.29)%比(57.03±0.27)%] (P> 0.05), 而在伤后24 h、48 h 致伤组脑组织含水量明显高于处理组,差异有统计学意义 [(67.41±0.37)%比(64.77±0.33)%, (81.95±0.47)%比(75.26±0.41)%](P<0.05)。在伤后 6 h 致伤组、处理组 MDA含量明显增加, 并且一直维持在较高水平, 而 SOD活性则明显下降, 与对照组比较差异有统计学意义 (P<0.05)。处理组在伤后6 h MDA含量和 SOD活性与致伤组比较差异无统计学意义(P>0.05), 而在伤后24 h、48 h MDA 含量显著降低[(130.39±7.02) μmol/g 比(149.41±8.25) μmol/g, (125.41±6.59) μmol/g 比(157.72±8.93) μmol/g], SOD活性则明显增高[(88.46±7.17)U/g比(80.10±4.87)U/g, (97.31±7.89)U/g 比(84.29±6.13) U/g], 差异均有统计学意义 (P<0.05)。结论 17β雌二醇对创伤性脑损伤有保护作用。     

通乐颗粒治疗慢性功能性便秘阴虚肠燥证临床研究

目的:观察通乐颗粒治疗慢性功能性便秘(chronic functional constipation,CFC)阴虚肠燥证的疗效及对血清超氧化物歧化酶(superoxide dismutase,SOD)和胃动素(motilin,MTL)的影响。方法:114例功能性便秘阴虚肠燥证患者按数字表随机分为治疗组57例和对照组57例。对照组参照《中国慢性便秘诊治指南》制定标准给予治疗;治疗组内服通乐颗粒每次12 g,2次·d-1;所有患者均给予4周治疗。比较两组中医临床症状评分和主要临床症状评分;检测两组血清SOD和MTL水平。结果:治疗组治疗后中医临床症状积分均显著低于对照组(P0.01);治疗组临床有效率为98.25%,对照组有效率为82.46%,两组比较,差异有统计学意义(P0.05);治疗组治疗后主要症状评分均低于同期对照组(P0.01);治疗组治疗后SOD和MTL水平均明显高于对照组,两组比较,差异有统计学意义(P0.01)。结论:通乐颗粒治疗CFC阴虚肠燥证可明显改善临床症状,提高临床疗效,升高血清SOD和MTL。     

Interactions between superoxide dismutase and paraoxonase polymorphic variants in nonsyndromic cleft lip with or without cleft palate in the Brazilian population

During development, oxidative stress is hypothesized to mediate embryotoxicity, which may be intensified by exposition to environmental factors and by genetic variations in the enzymes involved in protecting cells from these damaging effects, including superoxide dismutase (SOD) and paraoxonase (PON). The aim of this study was to evaluate the influence of single-nucleotide polymorphisms (SNP) in genes associated with the neutralization of oxidative stress (SOD and PON family members) in the risk of nonsyndromic oral cleft in the Brazilian population. Initially, we tested for association between 28 SNP in SOD1, SOD2, SOD3, PON1, PON2, and PON3 among 325 nonsyndromic cleft lip with or without cleft palate (NSCL±P) case-parent trios. Multiple logistic regression analyses were used to explore gene, GxG and GxE, involving factors that induce oxidative stress accumulation during pregnancy. Signals still significant after both Bonferroni correction and in permutation test were subsequently confirmed in an ancestry-structured case–control analysis with 722 NSCL±P and 866 controls from the same population. In the trio sample, transmission disequilibrium test (TDT) (allele and haplotype) and GxE analysis showed no significant associations, but multiple pairwise GxG interactions involving 10 SNP in PON1, PON2, and PON3 were detected and further examined in the case–control sample. The PON1 rs2237583 and PON2 rs17166879 yielded significant evidence of SNP-SNP interactions after adjustment for multiple tests (both Bonferroni correction and 10,000 permutation test). The C allele and the CT genotype of PON1 rs2237583 were associated with significant protective effects against NSCL±P, while rs3917490 showed a significant association only in the sample composed of patients displaying high African ancestry. Our results reveal associations between rs2237583 and rs3917490 in PON1 and GxG interactions containing rs2237583 and rs17166879 with the susceptibility of NSCL±P in the Brazilian population. Furthermore, this study underlines the recent tendency of taking into account potential GxG interactions to clarify the underlying mechanisms associated with the etiology of this common malformation. Environ. Mol. Mutagen. 60: 185–196, 2019. © 2018 Wiley Periodicals, Inc.