Study of the antioxidant enzymes in human brain tumors

Summary The activities of antioxidant enzymes i.e. Cu, Zn-SOD, Mn-SOD, CAT, and GSH-Px in the normal brain and brain tumors, as well as the two varieties of SOD in the mitochondria were examined and correlated to the histopathological diagnosis and the degree of malignancy of tumors. It was found that these scavenging enzymes of oxygen free radicals were expressed with great regularity in brain tumors. Both Cu, Zn-SOD and Mn-SOD were decreased in descending order in meningiomas, low grade astrocytomas, high grade astrocytomas and medulloblastomas. Furthermore, the reduction of Mn-SOD in mitochondria was proportionate to that of the whole tissues. While in contrast to the SODS, the CAT levels were significantly increased in ascending order in high grade astrocytomas, low grade astrocytomas and meningiomas. GSH-Px increased in meningiomas but not in gliomasAbbreviations SOD superoxide dismutase - Cu, Zn-SOD copper and zinc containing superoxide dismutase - Mn-SOD manganese containing superoxide dismutase - CAT catalase - GSH-Px glutathione peroxidase - GSH reduced glutathione - GSSG oxidized glutathione - RBC red blood cell     

α粒子诱发BEP2D细胞恶性转化中细胞内抗氧化蛋白和活性氧水平研究

目的：研究α粒子诱发永生化人支气管上皮细胞BEP2D恶性转化过程中细胞内主要抗氧化蛋白的表达和活性氧（ROS）水平以及DNA双链断裂水平的变化。方法：选择BEP2D细胞、RH22细胞和BERP35T-1细胞,采用Western blot检测细胞内抗氧化蛋白过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPXs）以及铜锌超氧化物歧化酶（Cu/Zn-SOD）和锰-SOD（Mn-SOD）的表达;采用SOD测定试剂盒检测细胞内总SOD（T-SOD）、Cu/Zn-SOD和Mn-SOD酶活力;荧光探针标记结合流式细胞仪检测细胞内基础H_2O_2和O_2~（？）水平;中性彗星电泳法检测细胞内DNA双链断裂水平。结果：与BEP2D细胞相比,RH22和BERP35T-1细胞内抗氧化蛋白CAT和GPX1表达下调（P〈0.05或P〈0.01）,GPX3、Cu/Zn-SOD和Mn-SOD表达增强（P〈0.05或P〈0.01）;且T-SOD、Cu/Zn-SOD和Mn-SOD活力均显著升高（P〈0.05或P〈0.01）。RH22和BERP35T-1细胞内基础O_2~（？）水平低于BEP2D细胞,基础H_2O_2和DNA双链断裂水平则高于BEP2D细胞（P〈0.05）。结论：细胞内氧化/抗氧化失衡形成氧化压力,促进DNA氧化损伤和基因组不稳定性,可能是α粒子诱发BEP2D细胞恶性转化的机制之一。     

High copper and iron levels and expression of Mn-superoxide dismutase in mutant rats displaying hereditary hepatitis and hepatoma (LEC rats)

The LEC rat is a mutant strain displaying hereditary hepatitisand hepatoma. We established enzyme-linked immunosorbent assaysof Cu, Zn- and Mn-superoxide dismutase (Cu,Zn- and Mn-SOD) andmeasured the levels of both SODs in various organs of LEC andWistar rats. Mn-SOD concentrations were higher in LEC rats thanin Wistar rats in most tissues. Cu,Zn-SOD levels of liver, kidneyand intestine were lower in LEC rats than in Wistar rats. Atomicabsorbtion techniques indicated that in addition to high Cuconcentrations as previously reported, LEC rat livers containedhigh Fe concentrations relative to those in Wistar rat livers.These data suggest that increased concentrations of Fe and Cuand decreased levels of Cu,Zn-SOD may facilitate the Fentonreaction to produce hydroxyl radicals in the tissues of theLEC rat. To compensate for the decreased scavenging effectsdue to low levels of Cu,Zn-SOD, an adaptive increase of Mn-SODmay occur in the process of hepatitis and hepatocarcinogenesisin LEC rats.     

Oral Concentrated Grape Juice Suppresses Expression of NF-kappa B,TNF-α and iNOS in Experimentally Induced Colorectal Carcinogenesis in Wistar Rats

The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane(AOM) and expression of NF-kB, iNOS and TNF- α. Methods: Forty male Wistar rats were divided into 7 groups:G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks beforeAOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juicewithout AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NFkB,TNF- and iNOS was evaluated by qPCR. Results: The number of ACF was higher in G2, and G4 presenteda smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lowerin G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed betweenTNF- α and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOMreduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animalsexposed to grape juice for a longer period of time, regardless of concentration.     

Marrow antioxidant enzyme activity in tumor-bearing and non-tumor-bearing mice following vincristine treatment

Pretreatment or "priming" with vincristine (VcR) has been documented to radioprotect animals from whole body irradiation by accelerating recovery of hematopoietic marrow. The mechanisms underlying this phenomenon are unclear, but the marked similarities between priming with VcR and with immune stimulants such as endotoxin and glucan have led to speculation that VcR may be inducing such radioprotective immunoregulators as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The radioprotective ability of these cytokines, in turn, has been linked to an induction of the antioxidant enzyme manganese superoxide dismutase (Mn SOD). To establish whether priming with VcR is associated with induction of antioxidant enzymes, the activities of Mn SOD, copper-zinc (Cu-Zn) SOD, catalase (CAT), and glutathione peroxidase (GPX) were measured in the marrow of both LLca tumor-bearing and non-tumor-bearing mice given a priming dose of VcR. Results in non-tumor-bearing mice indicate that, similar to IL-1 and TNF administration, VcR treatment increases Mn-SOD activity, but not Cu-Zn SOD, CAT, or GPX activity. Furthermore, this increase occurs at the time VcR priming has been demonstrated previously to exhibit maximal radioprotection, suggesting that it may be contributing factor. However, VcR priming has been demonstrated to radioprotect both tumor-bearing and non-tumor-bearing animals, and no increase in Mn SOD activity (or the other enzymes monitored) was found in the tumor-bearing group. Rather, the presence of tumor significantly suppressed antioxidant enzyme activity. Collectively, the present data suggest that it is unlikely that increased antioxidant enzyme activity is directly involved in the VcR priming response.     

Expression of Cu,Zn-SOD, Mn-SOD and GST-pi in oral cancer treated with preoperative radiation therapy

Radical scavengers play an important role in cancer cells defending themselves against free radicals which occur with irradiation. SOD (Cu,Zn, Mn-) and GST-pi are radical scavengers with an effect on radiation therapy. We investigated the correlation between radiation effects and expression of Cu,Zn-, Mn-SOD and GST-pi in 34 cases of oral cancer, treated with preoperative radiation therapy. In this study, 22 cases out of 34 were classified as effective and 12 cases as non-effective. Expression of Cu,Zn, Mn-SOD and GST-pi were observed in 13 (38.2%), 10 (29.4%) and 20 (58.8%) cases, respectively. Regarding the value of radiation sensitivity from expression of these proteins in the biopsy samples, no significant correlation was found between those expressions and histological effectiveness of preoperative radiation therapy. But interestingly, in 11 out of 12 of the non-effective cases, strong staining of Cu, Zn-SOD and GST-pi were shown at the residual cancer cells after preoperative radiation therapy. These results suggested that the expression of SOD (Cu,Zn-, and Mn-) and GST-pi may be not useful markers for predicting the effects of radiation therapy. However, Cu, Zn-SOD and GST-pi were increased by irradiation and may play an important role in radiation resistance and cancer cell regeneration after radiation therapy.     

Role of the antioxidant system and redox-dependent regulation of transcription factors bcl-2 and p53 in forming resistance of human K562 erythroleukemia cells to doxorubicin]

Prooxidant effect of chemotherapeutic agents is of significant interest in connection with activation of oxidative stress in cancer cells. Role of development of adaptive antioxidant response to the rise of resistance to cytotoxical effect of doxorubicin (DOX) has been studied in human erythroleukemia K562 cells. Growth of resistance to DOX caused enhancement of antioxidant enzymes (Cu, Zn-SOD, Mn-SOD, catalase) elevation of Mn-SOD activity being predominant. Additional increasing of antioxidant level was elevation of GSH maintenance and level of GST-related enzymes (glutathione peroxidase, glutathione S-transferase, glutathione reductase) in resistance K562/DOX cells. The enhancement of antioxidant system prevented activation of lipid peroxidation. Furthermore, the antioxidant growth caused decrease of level of proteintyrosine kinases, thioredoxin, thioredoxin reductase in contrary to elevation of glutaredoxin activity. Increasing of Bcl-2 and suppression of p53 levels was found to be caused by the change of redox state of K562DOX cells. The data support the suggestion that adaptive antioxidant response to prooxidant effect of DOX promotes the development of cellular drug resistance.     

The relation between superoxide dismutase in cancer tissue and clinico pathological features in breast cancer

The localization of Cu/Zn- and Mn-superoxide dismutase (SOD) in breast cancer tissue (12 papillotubular carcinomas, 21 solid-tubular carcinomas, 16 scirrhous carcinomas, 1 medullary carcinoma, 1 secreting carcinoma, 1 lobular carcinoma, 1 Paget's disease) was investigated via an immunohistochemical technique using antihuman Cu/Zn- and Mn-SOD antibodies in 10%formalin fixed-paraffin embedded thin sections. Both SODs stained strongly in the normal breast gland, but not clearly in many cancer tissues. Furthermore, Cu/Zn-SOD stained more strongly in well differentiated tubular carcinomas than in poorly differentiated tubular carcinomas. It tended to stain less in tumors which recurred or had a poor outcome, and in tumors with a diploid pattern on DNA flow cytometry. Mn-SOD staining was similar to that of Cu/Zn-SOD, but no significant differences among subgroups was found, since the incidence of positively staining tumors was too small in all groups. The intensity of SOD staining seems to change in relation to cell proliferation and differentiation in breast carcinoma, and may be a prognostic indicator, since SOD decreased in poorly differentiated carcinoma and in tumors which developed distant metastasis. Thus, the localization of SOD in breast cancer tissue can provide useful information for cancer treatment.     

Superoxide dismutases in relation to the overall survival of colorectal cancer patients.

Reactive oxygen metabolites are implicated in the initiation and promotion of cancer. In addition, oxidant scavengers, such as manganese--(Mn-SOD) and copper/zinc--superoxide dismutase (Cu/Zn-SOD), are thought to contribute to colorectal cancer treatment response. In the present study, the prognostic significance of the Mn- and Cu/Zn-SOD antigen content of normal mucosa and carcinomas of 163 patients with colorectal cancer was evaluated in comparison with major clinicopathological parameters, with respect to the 5-year overall survival. The Mn-SOD content of carcinomas was found to be significantly higher than that of normal mucosa, whereas there was no difference in the Cu/Zn-SOD content between the normal mucosa and carcinomas. No association was demonstrable between the Mn-SOD and Cu/Zn-SOD content of the tissues and the assessed clinicopathological parameters (gender, age, localization, differentiation grade, diameter and Dukes'' stage), with the exception of the Cu/Zn-SOD and the differentiation grade of the carcinomas. Univariate analysis showed that a high Mn-SOD content of carcinomas was associated with a poor 5-year overall survival of the patients with colorectal cancer. Multivariate analysis including all clinicopathological parameters revealed that this Mn-SOD parameter was prognostically independent. The Mn- and Cu/Zn-SOD content of normal mucosa and the Cu/Zn-SOD content of carcinomas were not associated with the overall survival of the patients. In conclusion, this study demonstrates that for patients with colorectal cancer the Mn-SOD content of colorectal carcinomas has a significant prognostic value that is independent from major clinicopathological parameters, including Dukes'' stage.     

芥菜籽对化学诱导小鼠大肠肿瘤形成过程中体内抗氧化状态的影响

  目的  通过观察小鼠体内自由基水平和抗氧化酶活性的影响, 探讨芥菜籽对氧化偶氮甲烷(azoxymethane, AOM)诱导的小鼠大肠肿瘤的预防作用机制。  方法  60只昆明品系小鼠随机分为AOM模型组、AOM+5%MS、AOM+10%MS干预组和正常对照组。观察记录各组小鼠肿瘤发生率; 检测小鼠血清中抗氧化酶(SOD、CAT、GSH-PX)的活力和脂质过氧化产物丙二醛(MDA)的水平。  结果  正常对照组小鼠无肿瘤发生。AOM模型组、5%MS和10%MS干预组三组间肿瘤发生率有差异(χ2=6.607, P=0.048);AOM模型组小鼠平均肿瘤数为(2.20±1.21)个, 而5%MS和10%MS干预组小鼠平均肿瘤数分别为(1.07±1.10)个和(0.67±0.89)个, 与模型组相比有显著性差异(P < 0.05)。小鼠血清抗氧化酶SOD、CAT、GSH-PX的活力: AOM模型组明显低于正常对照组(P < 0.05);MS干预组与AOM模型组相比均有所提高(P < 0.05);其中10%MS干预组提高小鼠血清抗氧化酶活力的作用最明显, 与5%MS干预组相比有显著性差异(P < 0.05)。小鼠血清脂质过氧化产物(MDA)含量: AOM模型组明显高于正常对照组(P < 0.05);MS干预组与AOM模型组相比均有所下降(P < 0.05);其中10%MS干预组降低小鼠血清MDA的效果最明显, 与5%MS干预组相比有显著性差异(P < 0.05)。  结论  芥菜籽能明显降低AOM诱导的小鼠大肠癌发生率并减少小鼠的平均肿瘤数, 且随芥菜籽浓度的增加, 其预防作用增强。芥菜籽能明显增强体内抗氧化的能力, 提高体内自由基清除酶的活性, 其预防机制可能与其抗氧化作用有关, 通过减少自由基对细胞的损伤, 预防基因突变和肿瘤发生。      

微量元素铜锌硒,抗氧化酶类,维生素E与恶性肿瘤的关系

本文作者对６７例恶性肿瘤患者同时作了血清铜（ＳＣｕ）、锌（ＳＺｎ）、硒（ＳＳｅ）含量和血红细胞超氧化物歧化酶（ＲＢＣ－ＳＯＤ）、谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活性及维生素Ｅ、丙二醛（ＭＤＡ）含量测定。     

红景天醇提物对乙醇诱导QZG细胞氧化损伤的保护作用

目的：研究乙醇对氧化应激损伤的作用特点和红景天醇提物的抗氧化作用。方法：采用DPPH自由基生成体系、体外鲁米诺化学发光反应（OH和O2-）体系观察红景天醇提物对DPPH自由基、OH和O2-化学发光强度的抑制作用以及剂量-效应关系。采用乙醇诱导人正常肝细胞系QZG细胞的氧化应激反应模型,观察红景天醇提物对乙醇诱导细胞活力和氧化应激损伤的保护作用。实验分设红景天醇提物3个不同浓度（50、100、200mg/L）的预防给药组和治疗给药组、阳性对照组（200 mmol/L乙醇干预）和阴性对照组（不加受试物）。预防给药组用红景天醇提物预处理QZG细胞12h后,再加入200mmol/L乙醇处理6h,治疗给药组采用红景天醇提物和乙醇同时处理QZG细胞6h。用MTT试验和生化法测定细胞活力、细胞丙二醛（MDA）、还原型和氧化型谷胱甘肽（GSH、GSSG）和总巯基（T-SH）含量、过氧化氢酶（CAT）、超氧阴离子歧化酶（SOD）活力;免疫印迹法检测细胞抗氧化酶血红素加氧酶-1（HO-1）和核因子相关因子2（NRF-2）蛋白的表达。结果：红景天醇提物对自由基的生成具有显著的抑制作用,呈现较为明显的剂量-效应关系;红景天醇提物可有效保护乙醇所致的肝细胞活力损伤,且治疗组具有明显的剂量-效应关系。与阳性对照组相比,红景天醇提物干预组细胞的MDA含量和GSSG含量下降（P〈0.05）,GSH和T-SH含量显著升高（P〈0.05）;CAT和SOD活性也显著升高（P〈0.05）。免疫印迹测定结果表明,红景天醇提物可以诱导HO-1蛋白和NRF-2蛋白表达上调（P〈0.05）。结论：红景天醇提物在体外自由基模型中具有较强的抗自由基作用,可保护乙醇导致的QZG细胞氧化损伤,其作用机制可能和抗氧化作用相关。     

Effects of timing and quantity of chronic dietary ethanol consumption on azoxymethane-induced colonic carcinogenesis and azoxymethane metabolism in Fischer 344 rats

Epidemiological studies have shown an association between consumption of alcoholic beverages and carcinoma of the large bowel, but studies in experimental models of colonic carcinogenesis have yielded conflicting results. We assessed the effects on azoxymethane-induced colonic carcinogenesis of both timing of chronic dietary ethanol consumption relative to carcinogen administration and quantity of ethanol consumption. Ten-week-old male Fischer 344 rats were given 11%, 22%, or 33% of calories as reagent ethanol or no ethanol by pair feeding with Lieber-DeCarli-type liquid diets providing comparable total carbohydrates, proteins, fats, and calories. Ten weekly s.c. injections of the bowel carcinogen azoxymethane (AOM), 7 mg/kg, were given to all rats in weeks 1-10. Three experimental groups were given their respective ethanol diet during acclimatization and AOM administration (preinduction and induction phases) and then were given the no-ethanol diet from week 11 until sacrifice in week 26 (postinduction phase). Three other groups received the no-ethanol diet during acclimatization and AOM administration and then were changed to their respective ethanol diet until sacrifice. The control AOM group received the no-ethanol diet throughout the study. Suppression of colonic tumorigenesis occurred in the groups with high levels of chronic dietary ethanol consumption during acclimatization and AOM administration: in the 33% and 22% diet groups, the prevalence of colonic tumors was 3% and 20% as compared with 50% in control (P less than 0.001 and P less than 0.02, respectively). Tumorigenesis in the left colon was more affected than in the right colon, as tumor prevalence in the left colon was decreased in both the 33% and 22% diet groups (0% in both versus 24% in control, P less than 0.005), whereas prevalence in the right colon was decreased only in the 33% diet group (3% versus 38%, P less than 0.001). By contrast, prevalence of colonic tumors in the 11% diet group was not significantly different from control. Chronic dietary ethanol consumption after AOM administration had no effect on tumor outcome, regardless of quantity of consumption. In an analogous study of [14C]AOM metabolism in rats fed the 33% diet during acclimatization and AOM administration, 14CO2 was exhaled at a slower rate than in rats fed no-ethanol diet (P = 0.05), indicating suppression of AOM metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)     

Protective effects of black tea extract on testosterone induced oxidative damage in prostate

Since ancient times, antipyretic, anti-inflammatory, antimicrobial and antioxidative properties of tea have been recognized. Black tea (Camellia sinensis) contains a variety of polyphenolic ingredients including the theaflavins (TF), thearubigins (TG) and catechins. Components from black tea have been accounted to play an important role in scavenging free radicals generated by mutagens and carcinogens. Androgens are the key factors in either the initiation or progression of prostate cancer (PCA) by inducing oxidative stress. In the present set of investigations, the antioxidative potential of black tea extract against androgen mediated oxidative stress in male Wistar rats has been studied. Testosterone was given at a dose of 5 mg/kg b.w. subcutaneously, consecutively for 5 days. Prior to androgen administration, animals were kept on 0.5, 1.0 and 1.5% aqueous tea extract (ATE) as sole source of drinking fluid for 15 days. The prostate tissue was dissected out for biochemical analysis for antioxidant enzymes viz. catalase (CAT), superoxide dismutase (SOD), lipid peroxidation (LPO), glutathione-s-transferase (GST) and glutathione reductase (GR). The results revealed that testosterone administration induced the oxidative stress in rat prostate, however, in 0.5, 1.0 and 1.5% ATE supplemented groups, a significant protective effect of black tea against testosterone induced oxidative injury was recorded. Hence, the study reveals that constituents present in black tea impart protection against androgen induced oxidative injury that may result in development of prostate cancer.     

Inhibition by dietary ethanol of experimental colonic carcinogenesis induced by high-dose azoxymethane in F344 rats

Epidemiological studies have shown an association between consumption of alcoholic beverages and increased occurrence of large bowel carcinoma, but studies in experimental models of colonic carcinogenesis have produced conflicting results. We assessed the effects of chronic dietary ethanol consumption during the preinduction and induction phase (period of acclimatization and carcinogen administration) in a high-dose azoxymethane-treated rat model (14 mg/kg/wk for 10 wk). Ten-wk-old male Fischer 344 rats were given 33% of calories as ethanol or no ethanol (controls). Pair-feeding with Lieber-DeCarli-type liquid diets provided comparable total carbohydrates, proteins, fats, and calories. After 3 wk of dietary acclimatization, injections of azoxymethane (AOM) were given s.c. to all rats in Wk 1 to 10. At necropsy in Wk 25, dramatic suppression of gastrointestinal tumorigenesis was evident in the ethanol-fed group: the prevalence of colonic tumors was 5% as compared with 91% in controls; and the prevalence of small bowel tumors was 0% versus 74% (P less than 0.0001). In an analogous study of [14C]AOM metabolism, exhaled 14CO2 was decreased in the ethanol-fed rats, indicating suppression of AOM metabolism. Similarly, in the ethanol-fed rats the levels of the DNA adducts O6-methylguanine and 7-methylguanine 24 h after AOM injection were reduced in the colonic mucosa to 14 +/- 7% and 61 +/- 11% of controls and in the liver to 80 +/- 9% and 86 +/- 6 of controls. By contrast, rats changed from the ethanol diet to no-ethanol diet for 12 h prior to the dose of [14C]AOM metabolized the carcinogen at a faster rate than controls, indicating loss of suppression with cessation of ethanol intake along with induction of metabolizing enzymes; DNA adduct levels were reduced in the colonic mucosa to 90 +/- 13% and 76 +/- 9% of controls and in the liver to 81 +/- 6% and 85 +/- 3% of controls. Our findings indicate that dietary ethanol during the preinduction and induction phase of the AOM model dramatically inhibits tumorigenesis, even with high dosage of carcinogen, and suggest that: (a) inhibition of tumorigenesis may result from suppression of metabolic activation of AOM and the consequent reduced formation of DNA adducts during the induction (initiation) phase of the model; (b) these anti-initiation effects of ethanol are unrelated to the epidemiological association between consumption of alcoholic beverages and large bowel cancer; and (c) mechanisms of action of agents found to modulate carcinogenesis in experimental models should be determined before the results can be generalized to human beings.     

Study of tobacco habits and alterations in enzymatic antioxidant system in oral cancer

AIM AND OBJECTIVE: Tobacco is a major etiological factor for oral cancer development, accounting 30-40% of all cancer cases in India. Tobacco consumption generates free radicals and causes oxidative damages. In order to counteract these lethal effects, normal living cells have multiple antioxidant defense systems in a cascade manner. Thus, it seems that studying biological parameters, like antioxidant enzyme system, may be helpful in risk assessment and early diagnosis of oral cancer. Therefore, we analyzed erythrocytic and tissue antioxidant enzyme activities in terms of glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and plasma thiol levels. MATERIALS AND METHODS: Study included healthy controls with no habit of tobacco (NHT, n = 25), controls with habit of tobacco (WHT, n = 31) and oral cancer patients (n = 52). All the parameters were analyzed with highly sensitive and specific spectrophotometric methods. RESULTS: Erythrocytic SOD and plasma thiol levels were significantly lower (p = 0.03), while GPx and CAT levels were higher (p = 0.017) in WHT as compared to NHT. No significant changes in GST and GR levels were observed between NHT and WHT. GST, GR, SOD and CAT activities were significantly higher (p = 0.05, p < 0.001, p = 0.003 and p < 0.001, respectively) while GPx and thiol levels were lower (p = 0.035 and p < 0.001, respectively) in oral cancer as compared to WHT. Odds ratio for erythrocytic GR, SOD, CAT and plasma thiol showed significantly higher risk of oral cancer development in WHT. Mean levels of SOD and CAT were increased, while GPx and thiol were decreased with the increase in habit duration in oral cancer. GST, GR and SOD activities were significantly higher (p = 0.0001, p = 0.005 and p = 0.005, respectively), while, CAT and thiol levels were lower (p = 0.0001 and p = 0.015, respectively) in malignant tissues as compared to adjacent normal tissues. CONCLUSION: The data revealed that evaluation of antioxidant enzyme activities and thiol levels in WHT can be helpful to identify individuals at a higher risk of oral cancer development     

Hepatoprotective effect of andrographolide against hexachlorocyclohexane-induced oxidative injury

Many plant products are known to exert antioxidative effects by quenching various free radicals and singlet molecular oxygen. Andrographis paniculata (Kalmegh) is used extensively in the Indian traditional system of medicine as a hepatoprotective and hepatostimulative agent and has been reported to have antioxidant effects against different hepatotoxins. The present study aims to analyze antioxidant properties of an active component, andrographolide (ANDLE), extracted from A paniculata. This study investigates the effect of andrographolide on the hepatocellular antioxidant defense system and lipid peroxidation of control mice, mice treated with hexachlorocyclohexane (BHC) only, and andrographolide + BHC. Glutathione (GSH), glutathione-s-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GSH-Px), gamma-glutamyl transpeptidase (gamma-GTP), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO) are studied by spectrophotometric methods. The BHC experimental model forms an irreversible liver tumor in male mice. The activities of GSH, GR, GSH-Px, SOD, and CAT show significant (P 相似文献   

The induction of ornithine decarboxylase by phorbol 12-myristate 13-acetate or by serum is inhibited by antioxidants

The mechanism of action of tumor promoters may involve the modulationof gene expression, e.g., the induction of ornithine decarboxyiase(ODC). The tumor promoter phorbol-13-myristate-12-acetate (PMA)induces chromosomal damage via the intermediacy of active oxygenspecies which may trigger the activation of certain genes. Therefore,we have studied the effect of antioxidants on the inductionof ODC by PMA, medium change only and medium change plus PMAin mouse mammary tumor cells Mm5mt/Cl. CuZn-superoxide dismutase(SOD, a scavenger of superoxide radicals), catalase (CAT, ascavenger of hydrogen peroxide) and mannitol (a scavenger ofhydroxyl radicals) suppressed ODC induction under all threeconditions. The relative inhibitory potency of the antioxidantswas always SOD > CAT > mannitol > SOD + CAT. Maximalsuppression by SOD + CAT was {small tilde}50%. It is concludedthat active oxygen species play a role in ODC induction by factorscontained in serum and by PMA.     

Oxidative stress is insignificant in N1S1-transplanted hepatoma despite markedly declined activities of the antioxidant enzymes.

It has been proposed that persistent oxidative stress accounts for the increased levels of DNA damage in cancer tissues. We have examined the profile of anti-oxidant enzymes in a transplanted hepatic tumor model by injecting N1S1 rat hepatoma cells into the liver of Sprague-Dawley rats. The transplanted N1S1 tumors displayed characteristics resembling human hepatocellular carcinoma. The immunoreactivities of catalase (CAT), manganese-superoxide dismutase (Mn SOD), copper/zinc-SOD (Cu/Zn SOD), and glutathione peroxidase (GPx) were found to decrease significantly. The enzyme activity in tumors decreased 26.2-, 4.2-, 4.5-, and 5.4-fold for CAT, Mn SOD, Cu/Zn SOD, and GPx, respectively, relative to those in normal liver tissue from the same animals. In contrast, the mRNA levels of CAT and GPx in tumors decreased only 5- and 2-fold, respectively, and the mRNA levels of Cu/Zn SOD and Mn SOD showed either no change or an increase as compared to those of normal liver tissue. The contents of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and thiobarbituric acid-reactive substances (TBARS) were comparable to those of normal controls. Furthermore, mitochondrial production of superoxide in tumors was 4 times lower than that in normal tissues. In conclusion, the data indicate that the reduced activities of anti-oxidant enzymes in the N1S1 tumor did not cause significant oxidative stress.