Chemopreventive Effects of Selenium on Cancer Marker Indices and Ultrastructural Changes During 1,2 Dimethylhydrazine-Induced Colon Carcinogenesis in Rats

Purpose

The present study was conducted to elucidate the potential of selenium supplementation, if any, in affording chemoprevention by modulating the altered cancer markers and ultrastructural changes in dimethyl hydrazine (DMH)-induced colorectal carcinogenesis in rats.

Methods

The rats were segregated into four groups, viz., normal control, DMH treated, selenium treated, and DMH + selenium treated. Initiation and induction of colon carcinogenesis was achieved through weekly subcutaneous injections of DMH (30 mg/kg body weight) for both 10 and 20 weeks. Selenium was supplemented to rats at a dose level of 1 ppm in drinking water ad libitum for two different time durations of 10 and 20 weeks.

Results

The study observed a significant increase in the number of aberrant crypt foci (ACF) in colons of DMH-treated rats at both time intervals which were decreased significantly upon selenium supplementation. Also, a significant increase was seen in the enzyme activity of alkaline phosphatase (ALP), which, however, was moderated upon selenium administration to DMH-treated rats. Changes in the ultrastructural architecture of colonic cells were apparent following both the treatment schedules of DMH; however, the changes were prominent following 20 weeks of DMH treatment. The most obvious changes were seen in the form of altered nuclear shape and disruption of cellular integrity, which, upon selenium supplementation, were appreciably improved.

Conclusion

In conclusion, the study shows the chemopreventive abilities of selenium against DMH-induced colorectal carcinogenesis in rats.     

Chemopreventive Effect of Amorphophallus campanulatus (Roxb.) Blume Tuber Against Aberrant Crypt Foci and Cell Proliferation in 1, 2-Dimethylhydrazine Induced Colon Carcinogenesis

Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigatedthe effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF)formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinicalmodel of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were dividedinto six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once aweek for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation,post- initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histologicalstudies. Administration of DMH resulted in significant (p≤0.05) intestinal and colonic lipid peroxidation (MDA)and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-Stransferaseand reduced glutathione. Whereas the supplementation of ACME significantly (p≤0.05) improvedthe intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes inDMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity ofACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreasedexpression of this proliferative marker was clearly noted with initiation, post-initiation and entire period ofACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effecton colon carcinogenesis induced by DMH.     

Prevention of N-methyl-N'-nitro-N-nitrosoguanidine and saturated sodium chloride-induced gastric carcinogenesis in Wistar rats by lycopene.

We investigated "the "chemopreventive potential of lycopene against gastric carcinogenesis induced in male Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl). Administration of lycopene inhibited MNNG+S-NaCl-induced gastric carcinogenesis as revealed by the absence of carcinomas. Lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) were used to monitor the chemopreventive potential of lycopene. The extent of lipid peroxidation was significantly lower, whereas GSH, GPx, GST and GR were markedly enhanced in the gastric mucosa of tumour-bearing animals. Our data suggest that lycopene may exert its inhibitory effects by modulating the oxidant and antioxidant status in the gastric mucosa.     

Effect of Brahma Rasayana on antioxidant systems and cytokine levels in mice during cyclophosphamide administration

Intraperitoneal administration of cyclophosphamide (CTX) 25 mg/kg.b.wt. dose/mouse for 10 days was found to suppress the tissue and serum level of reduced glutathione (GSH), blood glutathione peroxidase (GPX) and tissue levels of superoxide dismutase (SOD) and catalase (CAT). Tissue levels of glutathione reductase (GR) and glutathione-S-transferase (GST) were unaltered by CTX treatment while serum and tissue lipid peroxide levels were significantly increased. Oral administration of Brahma Rasayana BR-50 mg/dose/mouse for 10 days and 30 days significantly enhanced the tissue levels of SOD, CAT, GST, GPX, serum and tissue GSH and significantly reduced the serum and tissue lipid peroxidation. BR treatment was also found to enhance the serum cytokine level of interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and granulocyte macrophage-colony stimulating factor (GM-CSF) in normal and CTX treated mice. The results are indicative of the use of BR to reduce the oxidant stress induced by CTX treatment and its effect in cellular function.     

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     

Chemopreventive effect of trans-resveratrol--a phytoalexin against colonic aberrant crypt foci and cell proliferation in 1,2-dimethylhydrazine induced colon carcinogenesis

Prevention of cancer remains a primary need and new chemopreventive agents must be developed for this purpose. Towards this goal, a chemoprevention study was conducted to evaluate the activity of resveratrol (Res), a phytoalexin, as an inhibitor of colon carcinogenesis. Wistar male rats were divided into six groups, group 1 were control rats, group 2 were control rats that received Res (8 mg/kg body wt p.o. everyday), rats in groups 3-6 were treated weekly with 1,2-dimethylhydrazine (DMH, 20 mg/kg body wt, s.c. x 15 times). In addition, groups 4, 5 and 6 received Res as in group 2. Modifying effects were assessed using aberrant crypt foci (ACF) and the extent of histopathological lesions as end point markers. At the end of 30 weeks, Res markedly reduced tumor incidence, the degree of histological lesions and also the size of tumors significantly (P < 0.05) as compared with the rats treated with unsupplemented DMH. The number of ACF consisting of more than six aberrant crypts per rat was observed in group 6 (6.2 +/- 1.4), group 5 (7.7 +/- 1.0) and group 4 (8.2 +/- 1.4) which were significantly lower than that of group 3 (22.3 +/- 2.4) (P < 0.05). The most pronounced inhibition of ACF development was noted in rats fed Res for the entire period and also during the post-initiation period. Also, Res administration lowered the number of argyrophilic nucleolar organizing region-associated proteins (AgNORs) per nucleus in non-lesional colonic crypts, which reflects the cell proliferation activity. Oxidative imbalance in DMH-treatment was significantly (P < 0.01) modulated on Res supplementation as indicated by optimal concentration of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH). The results of our study suggest Res to be an effective chemopreventive agent, which suppresses DMH-induced colon carcinogenesis at various stages.     

Effect of thymoquinone on 1,2-dimethyl-hydrazine-induced oxidative stress during initiation and promotion of colon carcinogenesis

We evaluated pre- and post-thymoquinone (TQ) treatment on 1,2-dimethyl-hydrazine (DMH)-induced oxidative stress during initiation and promotion of colon carcinogenesis. Wistar rats were induced with DMH (20 mg/kg) for 10 or 20 weeks, and treated with TQ (5 mg/kg). Following sacrifice, the colons were analysed for tumour development, reactive oxygen species (ROS) generation, lipid peroxidation [conjugated diene (CD) and malondialdehyde (MDA)], antioxidants [glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH)], and histological changes. Increased ROS levels and lipid peroxidation were seen during tumour initiation and promotion. All ROS-scavenging enzyme activities were increased upon shorter DMH treatment but not following longer treatment, while GSH amount was increased upon both treatments. Oxidative state perturbations were associated with moderate colon dysplasia and 30% tumour incidence at initiation and marked dysplasia and 100% tumour incidence at promotion. TQ pre-treatment restored completely DMH-induced oxidative stress at initiation and established histological changes and tumour development. It also abrogated oxidative status aggravation at promotion, and significantly reduced tumour incidence (67%). By comparison, TQ post-treatment corrected oxidative status and attenuated tumour development at initiation. It slightly reduced MDA and antioxidant level at promotion, with a slight reduction in tumour state and dysplasia degree. TQ is efficacious in protecting and curing DMH-induced initiation phase of colon cancer, while exerting a protective role at promotion. TQ effect seems to be related to its capacity in preventing DMH-induced oxidative stress. These in vivo results support the notion that TQ may be of value as a chemo-preventive alternative in colorectal cancer patients.     

Protective Role of Selenium and High Dose Vitamin E against Cisplatin - Induced Nephrotoxicty in Rats

Background: Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer. Weinvestigated the effect of selenium (Se) with high dose vitamin E (VE) administration to prevent CDDP-inducednephrotoxicity in rats. Materials and Methods: In this study, 40 female Wistar rats were randomly dividedinto five equal groups. The first group, which served as the control, was administered physiological saline (2.5cc/day, 5 days) intraperitoneally (IP), while group A was administered cisplatin (6 mg/kg BW/ single dose)plus physiological saline IP. Groups B, C, D received IP five doses of Se (1.5 mg/kg BW), and a high dose ofVE (1000 mg/kg BW) (Se-VE) in combination before, simultaneously, and after CDDP, respectively. The ratswere sacrificed five days after CDDP administration. Plasma malondialdehide (MDA), glutathione peroxidase(GSH-Px), reduced glutathione (GSH), catalase, urea, creatinine levels, renal histopathological changes weremeasured. Results: The histopathological injury score, plasma levels of MDA, urea, creatinine were found toincrease in group A compared to the control (p<0.05), while plasma levels of GSH-Px, GSH and catalase decreased(p<0.05). In contrast, plasma levels of MDA decreased (p<0.05) in groups B, C, D, which were treated with Se-VE, whereas levels of GSH-Px, GSH were found to increase only for group D (p<0.05). Plasma urea, creatininelevels improved in the treatment groups compared to group A (p<0.001). Histopathological changes caused byCDDP were also significantly improved after Se-VE treatment (p<0.05). Conclusions: Oxidative stress increaseswith CDDP-induced nephrotoxicity in rats. Se-VE supplementation might thus play a role in the prevention ofCDDP-induced nephrotoxicity in patients.     

川芎嗪对辐射所致小鼠氧化应激损伤的保护作用

目的:研究川芎嗪对辐射所致小鼠氧化损伤的预防和治疗作用。方法:采用~(60)Co-γ射线5 Gy全身单次照射小鼠造模,分别于照射前(预防)和照射后(治疗)每天腹腔注射川芎嗪31.2 mg/kg,连续给药10 d,并设生理盐水阴性对照组,检测各组小鼠肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GPx)及总抗氧化力(T-AOC)的变化。结果:与阴性对照组比较,~(60)Co-γ射线照射可显著增加小鼠肝组织中MDA的含量(P0.05),降低SOD、GSH、GPx的活性(P0.05),使肝组织T-AOC下降(P0.05),但对CAT的活性无显著影响(P0.05)。与照射组比较,照射前和照射后给予川芎嗪,均可降低小鼠肝组织MDA含量(P0.05),使SOD、GSH、GPx的活性升高(P0.05)、肝组织T-AOC升高(P0.05),对CAT的活性仍无显著影响(P0.05)。结论:川芎嗪具有较好的抗氧化作用,预防和治疗性用药均可降低辐射所致小鼠的氧化应激损伤。     

Antioxidant potential by arabinoxylan rice bran, MGN-3/biobran, represents a mechanism for its oncostatic effect against murine solid Ehrlich carcinoma

We have recently examined the oncolytic effect of arabinoxylan rice bran, MGN-3/biobran, against solid Ehrlich carcinoma (SEC)-bearing mice via immune-modulation and apoptosis [N.K. Badr El-din, E. Noaman, M. Ghoneum, In vivo tumor inhibitory effects of nutritional rice bran supplement MGN-3/biobran on Ehrlich carcinoma-bearing mice, Nutr. Cancer 60 (2) (2008) 235-244]. In the present study, we examined the antioxidant system as another possible mechanism through which MGN-3 exerts its oncostatic potential. Female albino mice were inoculated intramuscularly in the right thigh with Ehrlich ascites carcinoma (EAC) cells. MGN-3 (25mg/kg body weight) was injected intraperitoneally (i.p.) six times a week for 25 days into mice at either day 4 or day 11 post-EAC cell inoculation. Tumor growth, lipid peroxidation (LPx), glutathione (GSH) contents, the activity of the antioxidant scavenger enzymes, and alterations in gene expression were examined. MGN-3 efficiently suppressed the growth of tumors, which was associated with normalization of the LPx levels and augmentation of GSH contents. MGN-3 enhanced the activity of the endogenous antioxidant scavenging enzymes - superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione-S-transferase (GST) - in blood, liver, and tumor tissue. Similarly it up-regulated the expression of GPx, SOD1 and CAT mRNA in the liver. The effect of MGN-3 was more pronounced when treated early, at day 4 of tumor cell inoculation, as compared to later treatment at 11 days. In conclusion, MGN-3-induced oncostatic activity by modulating lipid peroxidation, augmenting the antioxidant defense system and protecting against oxidative stress.     

Long term administration of granulocyte-macrophage colony stimulating factor decreases development of 1-2 dimethylhydrazine-induced colon cancer in rats

BACKGROUND AND OBJECTIVES: The antitumoral activities of granulocyte-macrophage colony stimulating factor (GM-CSF) were shown earlier. In this study, the effects of GM-CSF were investigated on colon cancer induced by 18 weeks of 1-2 dimethylhydrazine (DMH) administration in rats. METHODS: Four groups received subcutaneous saline (n = 20), 15 mg/kg DMH (n = 30), DMH +6 microg/kg GM-CSF (n = 30), and DMH +12 microg/kg (n = 30) GM-CSF. RESULTS: The average number of tumors (2.8 vs. 1.5) and mean tumor volume (179 +/- 36 vs. 27 +/- 9 mm(3); means +/- SEM) were reduced in DMH + GM-CSF groups as compared to the DMH group (n = 30, P < 0.01). DMH-induced enhancement of free radicals and lipid peroxidation were decreased in DMH + GM-CSF group (n = 8-12, P < 0.05). The magnitude of DMH-induced alterations in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was lowered in the DMH + GM-CSF group (n = 12-16, P < 0.05). DMH-induced increases in the total nitrite/nitrate levels and the nitric oxide synthase (NOS) activity (n = 10-12, P < 0.05) were also reduced in the DMH + GM-CSF group (n = 8-9, P < 0.05). CONCLUSIONS: The results indicate that GM-CSF inhibits the development of DMH-induced colon cancer in rats and suggest that inhibition of oxidative stress and NO pathway are involved in the observed antitumoral effects.     

Effects of vitamin E and selenium supplementation on esophageal adenocarcinogenesis in a surgical model with rats

Two well-known antioxidative nutrients, vitamin E and selenium, were used in this study to investigate possible inhibitory action against the formation of esophageal adenocarcinoma (EAC) in rats. In this model, carcinogenesis is believed to be driven by oxidative stress. Male Sprague-Dawley rats (8 weeks old) were divided into four groups and received esophagoduodenal anastomosis (EDA) surgery plus iron supplementation (12 mg/kg/week). Vitamin E and selenium were supplemented in the diet in the forms of alpha-tocopheryl acetate (750 IU/kg) and sodium selenate (1.7 mg Se/kg), which were 10 times the regular amounts in the basic AIN93M diet. At 40 weeks after surgery, all the EDA groups had lower body weights than the non-operated control group. Iron nutrition (hemoglobin, total serum iron and transferrin saturation) was normal as a result of iron supplementation after EDA. Vitamin E supplementation maintained the normal plasma level of alpha-tocopherol in EDA rats, but not those of gamma-tocopherol and retinol. Selenium supplementation increased the serum and liver selenium contents of the EDA rats. Histopathological analysis showed that selenium supplementation increased the incidence of EAC and the tumor volume. The selenium level in the tumor is higher than that in the duodenum of the same animal.Vitamin E supplementation, however, inhibited carcinogenesis, especially in the selenium-supplemented group. We believe that vitamin E exerts its effect through its antioxidative properties, and a high dose of inorganic selenium may promote carcinogenesis by enhancing oxidative stress.     

肿瘤与机体抗氧化系统

机体针对反应性氧族 (reactiveoxygenspecies ,ROS)产生的氧化损伤形成了一套抗氧化酶系统 ,包括超氧化物歧化酶 (superoxidedismutase ,SOD)、过氧化氢酶 (catalase ,CAT)、还原型谷胱甘肽 (reducedglutathione ,GSH)、谷胱甘肽过氧化物酶 (glutathioneperoxidase ,GPx)、谷胱甘肽 -S -转移酶 ( glutathionetransferase ,GST)等。它们在肿瘤的发生和发展中起到一定的作用 ,而肿瘤患者也常表现出抗氧化酶系统的失衡。就肿瘤与抗氧化系统的关系予以综述 ,为肿瘤的治疗提出一条新的思路     

Hepatoprotective Effects of Curcumin Against Diethyl Nitrosamine Induced Hepatotoxicity in Albino Rats

Curcumin is widely used as a traditional medicine. This work was aimed to investigate its possible protectiveeffect against chemically induced hepatocellular carcinoma (HCC) in rats. Fifty male albino rats were dividedinto five groups (n=10, each). The control group received a single dose of normal saline, the diethylnitrosamine(DENA) group received a single intra-peritoneal dose at 200mg/kg body weight, and the 3rd, 4th and 5th groupswere given DENA and daily administrated curcunine (CUR) via intra-gastric intubation in doses of 300,200and 100 mg/kg b.wt. respectively for 20 weeks. Serum, and liver samples were used for determination of alphafeto-protein (AFP), interleukin-2 (IL-2), interleukine-6 (IL-6), serum liver enzymes (AST, ALT, ALP and GGT)levels as well the activities and gene expression of glutathione peroxidise (GPx), glutathione reductase (GR),catalase (CAT) and super oxide dismutase (SOD). Curcumin significantly lowered the serum levels of AFP,IL-2 and IL-6, ALT, ALT, and malondialdehyde (MDA) as well gene expression of IL-2 and IL-6. In contrast itincreased the gene expression and activities of Gpx, GRD, CAT and SOD. The protective effect of CUR againstDEN-induced hepatocarcinogenesis in albino rats was proven.     

Impairment of antioxidant enzymes, lipid peroxidation and 8-oxo-2'-deoxyguanosine in advanced epithelial ovarian carcinoma of a Spanish community

In the present study, we describe the changes of antioxidant enzyme activities and other oxidative stress-related parameters in a mediterranean cohort of women affected with epithelial ovarian carcinoma (EOC). For that purpose, the most representative enzymatic activities, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the oxidized/reduced glutathione (GSSG/GSH) ratio have been analyzed in tumor tissue biopsies and compared with the normal tissue of the same patient. As oxidation products, the levels of malondialdehyde (MDA) as an indication of lipid peroxidation, and the DNA damaged base 8-oxo-2'-deoxyguanosine (8-oxo-dG) have been also measured. Advanced EOC show reduced levels of SOD and CAT, while that of GPx is increased when compared with non-neoplastic tissue. The levels of GSH are increased giving as a result a reduction of the oxidative stress marker GSSG/GSH ratio comparing normal ovarian tissue with tumor tissue. In addition, the oxidation products MDA and 8-oxo-dG are significantly increased in tumor tissue, suggesting a shift of oxidative metabolisms towards a pro-oxidation state and potential gene instability in malignant ovary cells. The possible implication of the redox changes and DNA damage in tumor development is discussed.     

Effects of garlic on 7,12-Dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

The inhibitory effect of garlic (Allium sativum Linn) on 7, 12-dimethylbenz[a]anthracene (DMBA)-induced buccal pouch carcinogenesis was investigated in male Syrian hamsters. Measurement of lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione S-transferase (GST) was used to monitor the chemopreventive potential of garlic. All hamsters painted on their buccal pouches with DMBA alone for 14 weeks developed well-differentiated squamous cell carcinomas. Diminished lipid peroxidation in the oral tumor tissue was accompanied by a significant increase in the levels of GSH, GPx, and GST. Administration of 250 mg/kg body weight aqueous garlic extract three times a week for 14 weeks effectively suppressed DMBA-induced oral carcinogenesis as revealed by the reduced incidence of neoplasms. The results of the present study suggest that garlic may exert its chemopreventive effects by modulating lipid peroxidation and enhancing the levels of GSH, GPx, and GST.     

Potential Prophylactic Effect of Berberine against Rat Colon Carcinoma Induce by 1,2-Dimethyl Hydrazine

Introduction: Colon Cancer remains one of the major worldwide causes of cancer related morbidity and mortalityin both genders. Berberine (BBR), a major component of alkaloids that possess a variety of pharmacological properties.Objective: This study shows the ameliorating roles of berberine on 1,2 Di methyl hydrazine (DMH) induced coloncancer in male Swiss albino rats. Methods: The rats were segregated into four groups: group 1, control rats; group2, rats were orally received berberine (75 mg/kg b.wt./day) daily for ten weeks; group 3,rats were subcutaneouslyinjected with DMH (20 mg/kg b.wt) once a week for 8 weeks ,group 4, rats were treated firstly with berberine fortwo weeks before DMH intoxication and concurrently with DMH over 8 weeks. Result: DMH injection decreasedthe antioxidants levels (GSH and SOD) and increased inflammatory markers (MPO, MAPK and COX-2). Moreover,it downregulated apoptotic markers (Caspase-3 and P53) expression that confirmed by colon cell proliferation. Theprophylactic effect of berberine was noticed as its pre-and co-administration increased antioxidants status and apoptoticmarkers expression that associated with inflammatory markers down-regulation with absence of proliferated coloncells. Conclusion: Therefore, the overall findings proved that the anti-proliferative effect of berberine return to itsantioxidants and anti-inflammatory properties that activated the programmed cell death process.     

硒对镉暴露大鼠肝脏氧化损伤的保护作用及机制研究

目的:探讨硒预处理对镉暴露大鼠肝脏氧化损伤的保护作用及其机制。方法:采用灌胃法建立大鼠镉暴露肝损伤模型。观察硒预处理对大鼠肝脏镉暴露相关氧化损伤的抑制作用并研究相关机制。通过检测血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)活性评价大鼠肝功能;通过免疫印迹法检测Bcl-2和Bax蛋白含量并计算Bax/Bcl-2的比值来判定大鼠肝脏细胞凋亡情况;通过肝组织冰冻切片DHE探针检测肝组织活性氧(ROS)水平和试剂盒测定脂质过氧化产物丙二醛(MDA)的含量研究大鼠肝脏氧化应激状态;通过试剂盒检测肝脏组织匀浆超氧阴离子歧化酶(SOD)及分型SOD-1活力、过氧化氢酶(CAT)和谷胱甘肽过氧化氢酶(GPx)的活力,免疫印迹检测抗氧化酶SOD-1、GP_x-1和CAT及抗氧化调控因子Nrf-2的蛋白水平评价大鼠肝脏抗氧化防御系统的功能。结果:与阴性对照组比较,硒预处理对镉暴露导致大鼠的血清ALT和AST升高具有显著的抑制作用(P均<0.05)。硒能抑制镉暴露导致的肝脏组织Bax/Bcl-2的升高(P<0.05),表明硒具有抑制镉导致的肝细胞凋亡的作用。硒预处理明显减缓了镉暴露导致的肝脏ROS水平和MDA水平的升高(P均<0.05),并引起抗氧化酶SOD和GPx活力的升高(P均<0.05),以及诱导核转录因子Nrf-2蛋白表达的上调(P<0.05),提示硒预处理能够有效地抑制镉暴露导致的肝脏氧化应激损伤作用。结论:硒对大鼠镉暴露导致的肝脏氧化损伤和细胞凋亡具有保护作用,其作用机制可能与增强机体抗氧化能力有关。     

Enhancement of pro-oxidant effect of 7,12-dimethylbenz (a) anthracene (DMBA) in rats by pre-exposure to restraint stress

The current study was designed to assess the effect of immobilization stress on liver toxicity induced by topical as well as oral administration of 7,12-dimethyl benz(a)anthracene (DMBA) in Swiss Albino rats. The experimental animals were divided into six groups. Group 1 animals were exposed to chronic restraint stress alone for 10 days (3 h/day), shaved back of animals in group II were painted with 0.5% solution of DMBA twice a week for 4 weeks. Group III animals were first exposed to restraint stress similar to group I followed by DMBA application as in group II, group IV animals were orally administered four doses of 0.5% DMBA solution. (1 ml/rat) at weekly intervals, while group V animals were first exposed to restraint stress as in group I followed by oral dose of DMBA similar to group IV. The untreated Group VI animals served as controls. Rats were sacrificed after a period of 4 weeks following DMBA administration. Biochemical measurements were carried out on liver tissues and serum/plasma of control and treated animals. Restraint stress was found to have marked effect on DMBA induced alteration of liver function as revealed by the increase in tissue marker enzymes viz glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), acid phosphatase (ACP), lactate dehydrogenase (LDH) with a significant further decrease in antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GR) as compared to controls and DMBA alone(topical/oral) or stress alone treated rats. Increased lipid peroxidation was accompanied by a significant decrease in the level of total reduced glutathione (GSH). The changes in the levels of marker enzymes and in vivo antioxidants in serum/plasma were comparable to that of liver. The results of the present study indicate that immobilization stress markedly enhances DMBA induced alteration of liver and circulatory antioxidant status of the rats irrespective of the mode of DMBA administration though with a predominant effect on orally infused DMBA.     

Protective Effect of Tomato Juice Against Mouse Skin Carcinogenesis

The anticarcinogenic effect of tomato juice, a natural source of antioxidants and other chemopreventive /antimutagenic agents, was studied in a skin carcinogenesis model in mice. The possible mode of action was alsoinvestigated. Oral administration of tomato juice afforded protection from development of skin tumour and increasedlife expectancy which may be attributed to the combined action of a number of chemical compounds with cancerchemopreventive properties present in tomato. The protective role may be associated with a decreased level of lipidperoxides noted in the tomato treated group and modulation of host detoxification enzymes. Exposure to the carcinogenresulted in a depression of the liver enzymes- glutathione-S-transferase (GST), glutathione peroxidase (GPx) andsuperoxide dismutase (SOD). Oral administration of tomato juice resulted in significant activation of all these enzymes(p<0.001). These results suggest a preventive role of tomato juice during carcinogenesis which is mediated possiblyby their modulatory effects on biotransformation enzymes and the detoxification system of the host.