氨氮和镉胁迫对芙蓉鲤鲫抗氧化系统和免疫机能的影响

为研究镉暴露对团头鲂免疫系统与抗氧化系统的影响, 将团头鲂暴露于浓度为0 (对照组)、0.05、0.10和0.50 mg/L 镉水体中养殖60d, 发现胆囊随镉浓度的增加而变大, 在高浓度镉暴露组(0.50 mg/L Cd)胆囊颜色加深变成墨绿色, 各镉暴露组团头鲂肝脏体指数与脾脏体指数均显著高于对照组, 且脾脏体指数随着镉浓度的增加逐渐升高。团头鲂经0.50 mg/L镉暴露养殖60d, 镉在肠中富集含量最高(240±1.41) mg/kg, 其次是中肾、肝、鳃、脾、头肾、心、精巢、卵巢和脑, 肌肉中镉的含量最低(0.35±0.04) mg/kg。团头鲂经0.50 mg/L镉暴露养殖60d后, 与对照组比较, 体色偏黄; 脾脏肿大, 细胞出现空泡; 肝脏发黑并有出血的症状, 肝窦增宽; 肠绒毛长度变短, 肠壁肌肉层厚度增大; 鳃组织出现动脉瘤, 细胞增生, 鳃小片发生弯曲。血清中谷胱甘肽过氧化物酶(GSH-PX)和总超氧化物歧化酶(SOD)活性随着镉浓度的增加逐渐降低, 溶菌酶(LYS)含量、碱性磷酸酶(AKP)、酸性磷酸酶(ACP)及过氧化氢酶(CAT)活性在低浓度镉暴露组显著升高, 在高浓度镉暴露组呈下降趋势, 且LYS含量、AKP与ACP活性在高浓度镉暴露组(0.50 mg/L)显著性低于对照组。il-6、il-1β、il-10、tnf-α与c3基因在头肾、脾脏及肝脏中的表达量随着镉浓度的增加逐渐降低, 肠中tnf-ɑ、c3与igm基因及鳃中c3基因的表达量均随着镉浓度的增加逐渐升高, 头肾中igm基因的表达量在低浓度镉暴露组显著升高, 在高浓度镉暴露组显著性降低。研究表明, 低浓度镉诱导团头鲂表现出一定的毒物兴奋效应, 但随着镉浓度增高, 团头鲂解毒与免疫相关组织被损伤, 机体抗氧化与免疫系统被抑制, 镉对团头鲂的抗氧化系统与免疫系统均存在毒性。研究为进一步深入探索镉对鱼类的毒性作用机制提供了基础的实验依据。

     

Molecular Effects of L-dopa Therapy in Parkinson’s Disease

Parkinson’s disease (PD) is one of the most common neurological diseases in elderly people. The mean age of onset is 55 years of age, and the risk for developing PD increases 5-fold by the age of 70. In PD, there is impairment in both motor and nonmotor (NMS) functions. The strategy of PD motor dysfunction treatment is simple and generally based on the enhancement of dopaminergic transmission by means of the L-dihydroxyphenylalanine (L-dopa) and dopamine (DA) agonists. L-dopa was discovered in the early -60''s of the last century by Hornykiewicz and used for the treatment of patients with PD. L-dopa treatment in PD is related to decreased levels of the neurotransmitter (DA) in striatum and ab-sence of DA transporters on the nerve terminals in the brain. L-dopa may also indirectly stimulate the receptors of the D1 and D2 families. Administration of L-dopa to PD patients, especially long-time therapy, may cause side effects in the form of increased toxicity and inflammatory response, as well as disturbances in biothiols metabolism. Therefore, in PD pa-tients treated with L-dopa, monitoring of oxidative stress markers (8-oxo-2’-deoxyguanosine, apoptotic proteins) and in-flammatory factors (high-sensitivity C-reactive protein, soluble intracellular adhesion molecule), as well as biothiol com-pounds (homocysteine, cysteine, glutathione) is recommended. Administration of vitamins B6, B12, and folates along with an effective therapy with antioxidants and/or anti-inflammatory drugs at an early stage of PD might contribute to improvement in the quality of the life of patients with PD and to slowing down or stopping the progression of the disease.     

Impact of depressive symptoms on oxidative stress in patients with psoriasis

Abstract

Background

Depression and anxiety disorders often accompany psoriasis. Increased reactive oxygen radicals and impaired antioxidant systems are considered to play a role both in psoriasis and depression and anxiety disorders. Accordingly, in this study, we aimed to investigate the effects of depressive and anxiety symptoms on oxidative stress in patients with psoriasis.

Materials and methods

Hospital Anxiety and Depression Scale (HADS) forms were completed by 39 psoriasis patients and 25 volunteer controls. Serum total antioxidant capacity (TAC) and total oxidant capacity (TOC) parameters were analysed in serum samples, after which oxidative stress index (OSI) was calculated in whole study population. Laboratory data were analysed with a Kruskal–Wallis test to determine the severity of HADS and the presence of psoriasis among four groups.

Results

The psoriasis patients had higher HADS scores, higher OSI and TOC levels, and lower TAC levels compared with the control group. Comparison among four groups with/without psoriasis and higher/lower HADS scores revealed statistically significant differences with regard to TAC (Kruskal–Wallis P = 0.0047) and TOC (Kruskal–Wallis P < 0.001) levels and OSI (Kruskal–Wallis P < 0.001); the difference was mainly based on the difference between cases with and without psoriasis and on HADS scores in control subjects (P < 0.05 for post hoc comparisons). TAC, TOC, and OSI levels did not differ significantly in psoriasis patients with regard to higher or lower HADS scores.

Conclusion

Based on the findings of this study, the presence of either psoriasis or higher HADS scores in the control subjects was associated with increased oxidative stress, whereas presence of higher HADS scores did not lead to further increase in oxidative stress in psoriatic patients.     

Effective immunotherapy against cancer

During the last decade, the breakthroughs in understanding of the molecular mechanisms responsible for immune activation and the advent of recombinant DNA technologies have changed the view on immunotherapy from a dream scenario to becoming a clinical reality. It is now clear that both cellular immunity comprising T and NK cells, as well as strategies based on antibodies, can provide strong antitumoral effects, and evidence is emerging that these strategies may also cure patients with previously incurable cancers. However, there are still a number of issues that remain unresolved. Progress in immunotherapy against cancer requires a combination of new, improved clinical protocols and strategies for overcoming mechanisms of immune escape and tumor-induced immune suppression. This review discusses some of the salient issues that still need to be resolved, focusing on the role of oxidative stress and the use of antioxidants to alleviate the immune hyporesponsiveness induced by reactive oxygen species (ROS).Abbreviations HLA Human leukocyte antigen - KIR Killer cell immunoglobulin-like receptor - NKR Natural killer cell receptor - ROS Reactive oxygen species - TAA Tumor-associated antigenThis work is part of the Symposium in Writing Tumor escape from the immune response, published in vol 53.     

Enhanced inflammatory responses in alpha-tocopherol transfer protein null mice

The liver preferentially secretes alpha-tocopherol into plasma under the control of the hepatic alpha-tocopherol transfer protein (alpha-TTP). alpha-TTP-null mice (Ttpa(-/-) mice) are vitamin E deficient, therefore were used for investigations of in vivo responses to sub-normal tissue alpha-tocopherol concentrations during inflammation. Increased basal oxidative stress in Ttpa(-/-) mice was documented by increased plasma lipid peroxidation, and superoxide production by bone marrow-derived neutrophils stimulated in vitro with phorbol 12-myristate 13-acetate. Lipopolysaccharide (LPS) injected intraperitoneally induced increases in lung and liver HO-1 and iNOS, as well as plasma NO(x) in Ttpa(+/+) mice. LPS induced more modest increases in these markers in Ttpa(-/-) mice, while more marked increases in plasma IL-10 and lung lavage TNF alpha were observed. Taken together, these results demonstrate that alpha-tocopherol is important for proper modulation of inflammatory responses and that sub-optimal alpha-tocopherol concentrations may derange inflammatory-immune responses.     

亮氨酸对抗阻运动引起的骨骼肌损伤和疼痛的保护作用

为了考察亮氨酸对抗阻运动引起的骨骼肌损伤和疼痛的影响,本研究通过建立抗阻运动骨骼肌损伤动物模型来考察亮氨酸对骨骼肌的保护作用,通过伊文氏蓝染色(evans blue stain,EBD)和苏木精和伊红染色(hematoxylin and eosin staining,HE)评价大鼠骨骼肌病理改变.发现亮氨酸给药明显减弱...     

Both oxidative and nitrosative stress are associated with muscle wasting in tumour-bearing rats

Reactive oxygen and nitrogen species (ROS and RNS) have been proposed as mechanisms of cancer-induced cachexia. In this study, we assessed using Western blot analysis the levels of total protein carbonylation (2,4-dinitrophenylhydrazine assay), both malondialdehyde- (MDA-) and 2-hydroxy-4-nonenal- (HNE-) protein adducts, Mn-superoxide dismutase (Mn-SOD), catalase, heme oxygenase-1 (HO-1) and 3-nitrotyrosine formation in gastrocnemius muscles of rats bearing the Yoshida AH-130 hepatoma. In the muscles of the tumour-bearing animals, protein carbonylation as measured by total levels of carbonyl group formation and both HNE and MDA-protein adducts, and protein tyrosine nitration were significantly greater than in control muscles. Protein levels of the antioxidant enzymes Mn-SOD, catalase, and HO-1 were not significantly modified in the rat cachectic muscles compared to controls. The inefficiency of the antioxidant enzymes in neutralizing excessive ROS production may account for elevated markers of protein oxidation and be responsible for the development of both oxidative and nitrosative stress in cancer-induced cachexia.     

Trikatu,an herbal compound as immunomodulatory and anti-inflammatory agent in the treatment of rheumatoid arthritis – An experimental study

In the present study, trikatu, an herbal compound was evaluated for its immunomodulatory and anti-inflammatory properties with reference to cell mediated immune responses (delayed type hypersensitivity reaction), humoral immune response (haemagglutination titer and plaque forming assay), macrophage phagocytic index, circulating immune complex and inflammatory mediators in rats. For comparison purposes, indomethacin was used as a reference drug for anti-inflammatory studies. The results obtained in our study showed a significant decrease in cell mediated immune responses, humoral immune responses (haemagglutination titre and plaque forming assay) and macrophage phagocytic index in trikatu treated rats (1000 mg/kg/b.wt.) compared to control animals implying its immunosuppressive property. In addition, significant anti-inflammatory effects were observed in trikatu treated adjuvant induced arthritic rats by a reduction in the levels of circulating immune complexes and inflammatory mediators (TNF-alpha and Interleukin-1beta). Thus, in conclusion, our data suggest that trikatu could be considered as a potential anti-inflammatory agent for treating autoimmune inflammatory disorders like rheumatoid arthritis with immunosuppressive property.     

Neopterin, a marker of immune response, and 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, correlate at high age as determined by automated simultaneous high-performance liquid chromatography analysis of human urine

Using an established high-performance liquid chromatography (HPLC) method based on anion exchange chromatography, fraction collection, and electrochemical detection, the oxidative DNA damage marker 8-hydroxy-2′-deoxyguanosine (8-OH-dG) can be analyzed rapidly and precisely in human urine samples. In addition, by ultraviolet (UV) detection, it was shown recently that it is possible to simultaneously analyze creatinine and 7-methylguanine (m⁷Gua), an RNA degradation product, in urine. By adding a fluorescence detector to the HPLC system, we now report that it is also possible to detect pteridins such as neopterin and biopterin. The fluorescence detection was evaluated in detail for neopterin, an immune response and tumor marker. The urinary content of neopterin, assessed by using the HPLC method, was verified with a commercial neopterin enzyme-linked immunosorbent assay (ELISA) kit as indicated by the high correlation between the two methods (r = 0.98). In urinary samples from 58 young healthy individuals (male and female nonsmokers, ages 19-39 years), it was found that there was no significant correlation (r = −0.04) between the levels of 8-OH-dG and neopterin (as normalized to urinary creatinine levels). In contrast, in urinary samples from 60 old healthy individuals (male and female nonsmokers, ages 60-86 years), there was a significant correlation (r = 0.47) found between the levels of 8-OH-dG and neopterin (as normalized to urinary creatinine levels). These findings strongly indicate that the higher level of immune response that was correlating with old age contributes significantly to the higher level of oxidative damage as assessed in the form of 8-OH-dG. Using this type of HPLC system, it is possible to evaluate oxidative DNA damage and immune response simultaneously using the respective urinary markers. These data may contribute to understanding of the pathophysiology of diseases such as infections and tumor progression where both oxidative stress and immune response occur simultaneously.     

氧化型胆固醇引起的血管平滑肌细胞氧化应激损伤研究

以胆固醇为对照,研究动脉粥样硬化症中常见的两种氧化型胆固醇（３β,５α,６β－三羟胆固烷、２５－羟胆固醇）对血管平滑肌细胞损伤及损伤机制。结果表明,于损伤早期,细胞的谷胱甘肽过氧化物酶活性增高,还原型谷胱甘肽含量减少。损伤后期谷胱甘肽过氧化物酶活性下降,细胞谷胱甘肽耗竭,细胞总巯基含量下降,细胞脂质过氧化产物含量和细胞羰基含量明显增高,表明细胞出现严重的氧化性损伤。而纯胆固醇,在与这两种氧化型胆固醇相同的作用时间,作用条件及剂量大于这两种氧化型胆固醇两倍以上的情况下,未曾引起细胞抗氧化酶、谷胱甘肽、蛋白质及脂质的任何明显改变。外给金属硫蛋白可减轻细胞损伤,外给Ｌ－ｂｕｔｈｉｏｎｅｉｎ－［Ｓ,Ｒ］－ｓｕｌｆｏｘｉｍｉｎｅ使细胞损伤加重,说明损伤与巯基含量有关。结果提示氧化型胆固醇引起的细胞损伤可能是通过氧应激产生。     

酒精性肝病发病过程中氧化应激指标的变化

目的酒精性肝病发病过程中氧化应激指标的变化。方法用酒精灌胃建立大鼠酒精性肝病模型,分别于4、8、12和16周留取血清和肝组织,用OLYMPUSAU-600全自动生化分析仪(日本)检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、胆碱酯酶(CHE);用生化比色法检测肝匀浆6-酮-前列腺素F1α(6-K-PGF1α)、血栓素B2(TXB2)、甘油三酯(TG)、氧自由基(ORF)、抗超氧阴离子(ASOA)、超氧化物歧化酶(SOD)及丙二醛(MDA)含量;用HE染色、苏丹Ⅳ染色和天狼星红染色观察肝组织病理学改变。结果随着病程进展,酒精性肝病大鼠肝脏呈现肝细胞脂肪变性、小叶内炎性坏死灶、窦周纤维化和汇管区纤维间隔形成等病理改变,血清ALT和AST逐渐升高,CHE降低,肝组织匀浆TG、OFR、MDA和TXB2含量逐渐升高,SOD、ASOA和6-K-PGF1α降低,与正常对照组比较P<0·05或P<0·01。结论ALD发病过程中存在氧化应激,氧化应激在酒精性肝病发病中发挥着重要作用。