The selective tyrosine kinase-inhibitor nilotinib alleviates experimentally induced cisplatin nephrotoxicity and heptotoxicity

This work tested the action of nilotinib, selective inhibitor of tyrosine kinase on cisplatin (CP)-induced damage of kidney and liver in rats. Rats were assigned to 4 groups, control, nilotinib, CP, and CP plus nilotinib. Assessment of kidney and liver function, lipid peroxidation and antioxidant markers, anti-apoptotic protein Bcl2, nuclear factor- kappa B (NF-κB) immunoreactivity, and caspase 3 activity were done. CP-induced damage evidenced by histopathological changes, deterioration of renal and liver function, imbalance in oxidants/antioxidants markers, decreased Bcl2, increased caspase 3 activity, and NF-κB nuclear expression in both organs. Nilotinib treatment with CP restored kidney and liver oxidants/antioxidant levels also increased Bcl2 and decreased NF-κB immunoreactivity were evident with nilotinib treatment. In conclusions these results demonstrated a protective effect of nilotinib in experimentally induced CP kidney and liver damage that could be mediated through combating oxidative stress, reducing inflammation and anti-apoptosis in the two organs.     

Resveratrol attenuates cisplatin renal cortical cytotoxicity by modifying oxidative stress

Cisplatin, a cancer chemotherapy drug, is nephrotoxic. The aim of this study was to investigate whether resveratrol (RES) reduced cisplatin cytotoxicity and oxidative stress. Rat renal cortical slices were pre-incubated 30 min with 0 (VEH, ethanol) or 30 μg/ml RES followed by 60, 90 or 120 min co-incubation with 0, 75, or 150 μg/ml cisplatin. Lactate dehydrogenase (LDH) leakage was unchanged at 60 and 90 min by cisplatin. Cisplatin increased (p < 0.05) LDH leakage at 120 min which was protected by RES. Cisplatin induced oxidative stress prior to LDH leakage as cisplatin depressed glutathione peroxidase and superoxide dismutase (SOD) activity, increased lipid peroxidation, protein carbonyls and 4-hydroxynonenal (4-HNE) adducted proteins within 60 min. RES failed to reverse glutathione (GSH) depression by cisplatin. In order to eliminated an extracellular interaction between RES and cisplatin, additional studies (RINSE studies) allowed a 30 min RES uptake into slices, transfer of slices to buffer lacking RES, followed by 120 min cisplatin incubation. RES in the RINSE studies prevented LDH leakage by cisplatin indicating that RES protection was not via a physical interaction with cisplatin in the media. These findings indicate that RES diminished cisplatin in vitro renal toxicity and prevented the development of oxidative stress.     

咽后壁瓣修复术后并发阻塞性睡眠呼吸暂停的临床研究

探讨腭裂术后腭咽闭合不全（VPI）患者行咽后壁瓣修复术（PFS）后阻塞性睡眠呼吸暂停（OSA）的发生率及严重程度，并探讨手术年龄对OSA发生率及严重程度的影响。     

辛伐他汀强化治疗对急性冠脉综合征患者炎症状态及氧化应激水平的影响

目的:观察辛伐他汀强化治疗对急性冠脉综合征患者血浆炎症状态及氧化应激水平的影响。方法:选取64例急性冠脉综合征患者,随机分为2组,常规治疗组服用20mg常规剂量辛伐他汀,强化治疗组患者于住院期间服用40mg强化治疗,出院后服用20mg治疗。并设健康对照组(无任何干预措施)。服药前后检测C反应蛋白(CRP)、丙二醛(MDA)、过氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)。结果:2组患者治疗后各项指标均较治疗前显著改善(P<0.05)。强化治疗组与常规治疗组患者血浆中MDA、SOD水平、GSH-Px活性在出院时即有显著性差异(P<0.05),CRP水平在出院后第4周时有显著性差异(P<0.05),出院8周后2组间上述所有指标间差异仍有统计学意义(P<0.05),出院12周时,差异无统计学意义(P>0.05)。结论:大剂量辛伐他汀短期强化治疗抗炎和抗氧化应激的保护作用更明显。     

Antioxidative Potential of Duranta Repens (Linn.) Fruits Against H2O2 Induced Cell Death In Vitro

The effects of Duranta repens fruits were investigated on H₂O₂ induced oxidative cell death to evaluate its antioxidative potential in vitro. HEK293T cells were treated with different concentrations [0–1000 µg/ ml] of ethanol extract (E-Ex) and methanol extract (M-Ex) of D. repens for 24h, and then treated with 100 µM H₂O₂ for 24h. Cell viability, antioxidant parameters of cells, and antioxidant constituents of the extracts were determined. Treatment with limited dose of E-Ex or M-Ex increased the survival rate of H₂O₂-treated HEK293T cells, however the extra-high dose showed growth inhibitory effect. Treatment with E-Ex or M-Ex protected cellular lipid per-oxidation. In vitro analyses showed the 2,2-diphenyl-1-picrylhydrazyl and H₂O₂ scavenging activities as well as reducing potential of the extracts. We report here that the limited dose of E-Ex and M-Ex possess antioxidative potential, which can protect H₂O₂-induced oxidative cell damage.     

视网膜母细胞瘤组织中DNA甲基转移酶1、DNA甲基转移酶3a、3b的表达

目的 观察视网膜母细胞瘤(RB)组织中DNA甲基转移酶(DNMT)1、DNMT3a和DN MT3b的表达.方法 62例RB肿瘤组织标本及6例正常视网膜组织标本纳入研究.其中,低分化组织标本17例,高分化组织标本45例；侵袭性肿瘤16例,非侵袭性肿瘤46例.采用免疫组织化学染色方法检测RB肿瘤组织标本中DNMT1、DNMT3a、DNMT3b的表达.以细胞核棕色染色为阳性表达,蓝色为阴性表达.以DNMT1、DNMT3a及DNMT3b阳性细胞分别≥65％、60％及40％为DNMT1、DNMT3a、DNMT3b高表达,≥1％但＜65％、60％及40％为低表达.同时分析DNMT1、DNMT3a、DNMT3b表达和MIB-1标记指数之间的相关性.结果 光学显微镜观察发现,正常视网膜组织中DNMT1、DNMT3a和DNMT3b均为阴性表达.肿瘤视网膜组织中均可见DNMT1、DNMT3a和DNMT3b表达,其阳性表达率分别为100％、98％、92％.高低分化组织标本比较,DNMT1、DNMT3a高表达率(x2=12.57、10.54)及阳性细胞计数(U=179、198)间差异均有统计学意义(P＜0.05)；DNMT3b高表达率(x2=1.5)和阳性细胞计数(U=307)间差异均无统计学意义(P＞0.05).侵袭性及非侵袭性肿瘤组织标本比较,DNMT1高表达率(x2=4.72)及阳性细胞计数(U=236)间差异均有统计学意义(P＜0.05)；DNMT3a、DNMT3b高表达率(x2=3.53、0.84)及阳性细胞计数(U=338、257)间差异均无统计学意义(P＞0.05).相关性分析结果显示,MIB-1标记指数与RB肿瘤组织中DNMT1、DNMT3a及DNMT3b表达呈正相关(R2=0.554、0.376、0.219,P＜0.05).结论 RB肿瘤视网膜组织中DNMT1、DNMT3a和DNMT3b均呈高表达.     

Mussel oligopeptides ameliorate cognition deficit and attenuate brain senescence in d-galactose-induced aging mice

Dietary supplementation exerts beneficial effects in reducing incidence of chronic neurodegenerative diseases. The purpose of this study was to examine protective effects of mussel (Mytilus edulis) oligopeptides supplementation on brain function in d-galactose induced aging mice. Sixty female 8-month-old mice were randomly divided into five groups: vehicle control, d-galactose, and d-galactose combined with 200, 500, 1000 mg/kg mussel oligopeptides. The results showed that mussel oligopeptides could improve cognitive learning and memory ability and protect the hippocampal neurons. In addition, GSH, SOD and GSH-pX activities were increased and MDA level was significantly decreased in mice fed with mussel oligopeptides. It was also found that mussel oligopeptides supplementation prevented d-galactose-induced elevations of iNOS activity and NO production and lactate acid levels in brain. Moreover, PI3K and Akt genes were up-regulated by mussel oligopeptides supplementation. These findings suggest that mussel oligopeptides are able to enhance exercise capacity and protect against oxidative damage caused by d-galactose in aging model mice through regulating oxidation metabolism and PI3K/Akt/NOS signal pathway. Therefore, mussel oligopeptides are good materials for future development of healthcare products to combat age-related brain dysfunction and to improve healthy life span.     

Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice were given tests for spatial learning (Morris water maze), spontaneous locomotor activity, motor coordination, and startle reflex. Age-related impairments in cognitive and psychomotor functions were evident in the 17.5-month-old mice fed the control diet, and the low-CoQ diet failed to affect any aspect of the impaired performance. However, in the Morris water maze test, old mice on the high-CoQ diet swam to the safe platform with greater efficiency than the mice on the control diet. The old mice supplemented with the high-CoQ diet did not show improvement when spatial performance was measured using probe trials and failed to show improvement in other tests of behavioral performance. Protein oxidative damage was decreased in the mitochondria from the heart, liver, and skeletal muscle of the high-CoQ-supplemented mice and, to some extent, in the brain mitochondria. Contrasting with the deleterious effect of long-term CoQ supplementation initiated during young adulthood previously published, this study suggests that CoQ improves spatial learning and attenuates oxidative damage when administered in relatively high doses and delayed until early senescence, after age-related declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, high-CoQ intake may be beneficial.