I405V and TaqIB polymorphisms of the cholesteryl ester transfer protein and their relation to serum lipid and lipoprotein levels in a Turkish population.

Cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein (HDL) metabolism. Genetic polymorphisms of the CETP gene can influence levels of serum lipoproteins. It has been reported that mean HDL-cholesterol (HDL-C) concentrations are low in Turkish population. Thus, we investigated the frequencies of the common I405V and TaqIB polymorphisms of the CETP gene and their relation to serum lipid and lipoprotein levels in a Turkish population. The variant allele frequencies of I405V and TaqIB polymorphisms of the CETP gene were found to be 0.38 and 0.46, respectively and similar to some of the European populations. Subjects for the VV genotype of I405V polymorphism had higher HDL-C levels than did II subjects. The covariance analysis showed that gender and triglyceride (TG) levels have an effect on the association of HDL-C and I405V polymorphism. In conclusion, our results indicate that I405V polymorphism may affect the HDL-C levels in Turkish population. The association of this polymorphism and HDL-C levels could be modified by other factors, such as gender and TG levels.

The role of heat shock protein 70 (Hsp 70) in male infertility: is it a line of defense against sperm DNA fragmentation?

OBJECTIVE: To clarify the role of heat shock protein 70 (Hsp 70) and its relation with DNA damage in male infertility. DESIGN: Prospective study. SETTING: Andrology laboratory of Istanbul Medical Faculty. PATIENT(S): Semen samples from 37 infertile men and 13 fertile men (as controls). INTERVENTION(S): The percentage of DNA fragmentation was assayed with the use of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). Sperm Hsp 70 expression was determined by using Western blot analysis. MAIN OUTCOME MEASURE(S): Both the percentages of sperm DNA fragmentation and Hsp 70 expression were correlated with semen analysis parameters. RESULTS: TUNEL-positive spermatozoa in the infertile group (18.7% for asthenospermics and 13.0% for oligoasthenospermics) were higher than the fertile group (4.9%). Significant inverse correlations were detected between percentage of TUNEL-positive cells and both concentration (r = -0.487) and motility (r = -0.377) of spermatozoa. No expression of Hsp 70 was observed in azospermic group, whereas Hsp 70 levels were found increased significantly in infertile group (U = 62 for asthenospermics and U = 38 for oligoasthenospermics) compared to fertile group as analyzed by using Mann-Whitney U Wilcoxon rank sum test. Furthermore, significant positive correlation was found between percentage of TUNEL-positive cells and Hsp 70 expression (r = 0.357). CONCLUSION(S): Hsp 70 expression may have been increased as a protective mechanism against apoptosis in spermatozoa of infertile men.

Effect of heme oxygenase-1 induction by octreotide on TNBS-induced colitis.

BACKGROUND AND AIM: Ulcerative colitis is a chronic inflammatory disease of the colon and rectum. Although the precise etiology of ulcerative colitis remains unknown, it is believed to involve an abnormal host response to endogenous or environmental antigens, genetic factors, and oxidative damage. The aim of the present study was to investigate whether heme oxygenase-1 (HO-1) induction by octreotide could protect against oxidative and inflammatory damage from induced colitis. METHODS: Rats received octreotide 50 microg/kg per day intraperitoneally for 5 days before 2,4,6 trinitrobenzene sulfonic acid (TNBS) solution administration and for 15 days following TNBS solution administration. Rats were killed on day 21, and colonic malondialdehyde (MDA) levels, glutathione (GSH) levels and HO-1 expression were measured. Nuclear factor (NF)-kappaB and HO-1 expression was evaluated by immunohistochemical examination of the colonic tissue. RESULTS: Rats with TNBS-induced colitis had significantly increased colonic MDA levels and HO-1 expression in comparison to the control group. Octreotide treatment was associated with increased HO-1 expression and GSH levels, but decreased MDA levels. Histopathological examination revealed that the intestinal mucosal structure was preserved in the octreotide-treated group. In addition, treatment with octreotide significantly increased HO-1 expression and decreased NF-kappaB expression by immunohistochemistry when compared to the TNBS-induced colitis group. CONCLUSION: Octreotide appears to have protective effects against colonic damage in TNBS-induced colitis. This protective effect is, in part, mediated by modification of the inflammatory response and the induction of HO-1 expression.

Nitrotyrosine formation and heme oxygenase-1 expression in endotoxemic cirrhotic rats.

BACKGROUND: Endotoxemia increases hepatic toxicity and mortality in cirrhosis. Because the mechanism of augmented hepatotoxicity in endotoxemic cirrhotic rats is still unclear, we wanted to investigate whether oxidative and nitrosative stress play a causative role in lipopolysaccharide (LPS)-treated cirrhotic rats. METHODS: Liver cirrhosis was produced by the administration of thioacetamide (0.3 g/L of tap water) for a period of 3 months in rats. At the end of this period, cirrhotic rats were sacrificed 6 h after LPS injection (5 mg/kg, intraperitoneally). Serum transaminase activities, plasma total nitrite and nitrotyrosine (NT) levels as well as hepatic lipid peroxides, NT formation and heme oxygenase 1 (HO-1) expression were determined. RESULTS: LPS administration to cirrhotic rats caused further increases in serum transaminase activities, and plasma total nitrite and NT levels as well as hepatic lipid peroxide levels as compared to cirrhotic rats. Hepatic NT formation and HO-1 expression were also found to be increased in LPS-injected cirrhotic rats. CONCLUSIONS: Our results indicate that increased oxidative and nitrosative stress may have a synergistic effect in LPS-augmented hepatotoxicity in cirrhotic rats.

The effect of heme oxygenase-1 induction by glutamine on TNBS-induced colitis. The effect of glutamine on TNBS colitis.

BACKGROUND: Inflammatory bowel disease is a multifactorial inflammatory disease of the colon and rectum with an unknown etiology. In the present study, we aimed to investigate whether heme oxygenase-1 (HO-1) induction by glutamine could protect colitis-induced damage from oxidative, inflammatory, and apoptotic damage. METHOD: The rats were divided into four groups. Group 1 had TNBS colitis alone, group 2 had TNBS-induced colitis and glutamine 1 g/kg/day intragastric gavage for 3 days before TNBS solution administration and 15 days following TNBS solution administration, group 3 had glutamine alone 1 g/kg/day intragastric gavage for 18 days before being killed, and group 4 had isotonic saline solution alone 1 cm3/rat intragastric gavage for 18 days before being killed. Colonic malondialdehyde (MDA) levels, glutathione (GSH) levels, caspase-3 activities, and HO-1 expressions of the killed rats were measured. Nuclear factor kappa B (NF-kappaB) and HO-1 expression were evaluated by immunohistochemical examination of the colonic tissue. RESULT: TNBS-induced colitis significantly increased the colonic MDA levels, caspase-3 activities, and HO-1 expression in comparison to the control group. Glutamine treatment was associated with increased HO-1 expression and GSH levels and decreased MDA levels and caspase-3 activity. Histopathological examination revealed that the intestinal mucosal structure was preserved in the glutamine-treated group. In addition to this, treatment with glutamine significantly increased HO-1 expression and decreased NF-kappaB expression by immunohistochemistry when compared to the TNBS-induced colitis group. CONCLUSION: Glutamine reduced colonic damage in TNBS-induced colitis. The mechanism of the protection associated with glutamine was due to antioxidant, antiapoptotic, anti-inflammatory, and HO-1 induction effects.

The effect of octreotide on pancreatic damage in TNBS-induced colitis.

Inflammatory bowel disease, a chronic condition of the intestine, is associated with numerous extraintestinal manifestations, including pancreatitis. This study investigated the effect of octreotide administration on oxidative damage in a rat model of colitis induced by 2,4,6-trini-trobenzene sulfonic (TNBS) acid. Colonic and pancreatic malondialdehyde and glutathione levels are indicators of oxidative damage, and TNBS-induced colitis significantly increased the colonic and pancreatic malondialdehyde levels and decreased glutathione levels. Octreotide treatment was associated with decreased malondialdehyde levels and increased glutathione levels in the colonic and pancreatic tissue. The colonic mucosal structure was preserved and pancreatic inflammation decreased in rats treated with octreotide. Octreotide also significantly decreased nuclear factor-kB expression by immunohisto-chemistry in the colonic and pancreatic tissue compared with TNBS-induced colitis group. Octreotide appears to have protective effects against TNBS-induced colonic and pancreatic damage. These results imply the reduction in mucosal damage owing to the anti-inflammatory and antioxidant effects of octreotide.

The effect of glutamine on pancreatic damage in TNBS-induced colitis.

Ulcerative colitis is a multifactorial inflammatory disease of the colon and rectum with an unknown etiology. The present study was undertaken to investigate the effect of glutamine administration on oxidative damage and apoptosis in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Rats received 1 g/kg/day glutamine for intragastric gavage for 7 days before TNBS solution administration and 3 days following TNBS solution administration until sacrifice. Then colonic and pancreatic malondialdehyde (MDA) and glutathione (GSH) levels, and colonic caspase-3 activities of the sacrified rats were measured. TNBS-induced colitis caused significantly increased in the caspase-3 activity and colonic and pancreatic MDA levels and decreased colonic and pancreatic GSH levels compared to those in the sham group. Glutamine treatment was associated with decreased MDA levels and caspase-3 activity and increased GSH levels in the colinic and pancreatic tissue. Histopathological examination revealed that the colonic mucosal structure was preserved and pancreatic inflammation decreased in the glutamine-treated group. In conclusion, glutamine appears to have protective effects against TNBS-induced colonic and pancreatic damage. These results imply a reduction in mucosal damage due to anti-inflammatory and antiapoptotic effects of glutamine.

The effect of melatonin on TNBS-induced colitis.

Ulcerative colitis is a multifactorial inflammatory disease of the colon and rectum with an unknown etiology. The present study was undertaken to investigate the effect of melatonin administration on oxidative damage and apoptosis in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Rats were divided into four groups as follows: Group 1 (n=8)-T-NBS colitis; Group 2 (n=8)--melatonin, 10 mg/kg/day ip, for 15 days in addition to TNBS; Group 3 (n=8)--melatonin alone, 10 mg/kg/day ip, for 15 days; and Group 4 (n=8)-isotonic saline solution, 1 ml/rat ip, for 15 days (sham control group). Colonic myeloperoxidase (MPO) activities, malondialdehyde (MDA) levels, and glutathione (GSH) levels are indicators of oxidative damage, while caspase-3 activities reveal the degree of apoptosis of the colonic tissue. In all TNBS-treated rats, colonic MPO activity and MDA levels were found to be increased significantly compared to those in the sham group. Colonic MPO activity and MDA levels were significantly lower in the melatonin treatment group compared to TNBS-treated rats. GSH levels of colonic tissues were found to be significantly lower in TNBS-treated rats compared to the sham group. Treatment with melatonin significantly increased GSH levels compared to those in TNBS-treated rats. Caspas-3 activity of colonic tissues was found to be significantly higher in TNBS-treated rats compared to the sham group. Treatment with melatonin significantly decreased caspase-3 activity compared to that in TNBS-treated rats. These results imply a reduction in mucosal damage due to anti-inflammatory and anti-apoptotic effects of melatonin.

Polymorphisms in the DNA repair genes XPD (ERCC2) and XPF (ERCC4) are not associated with sporadic late-onset Alzheimer's disease.

Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair, recognizing and dealing a variety of helix-distorting lesions. Xeroderma pigmentosum group D (XPD) and group F (XPF) are essential participants in NER pathway. There is evidence that two common polymorphisms of XPD gene (g.22541C>A; exon 6 and g.35931A>C; Lys>Gln; exon 23) may be associated with differential DNA repair activities. Alzheimer's disease (AD) is characterized by progressive neuronal loss correlated in time with the symptoms of disease considered. Although deficient DNA repair was proposed in the etiology of AD by several researchers, polymorphisms of DNA repair genes have not been studied in AD yet. We conducted a case-control study including 97 patients with AD and age- and sex-matched 101 control subjects to examine the role of genetic polymorphisms of XPD and XPF (g.30028T>C; exon 11) as a risk factor for AD. The frequencies of the XPD/exon 6, XPD/exon 23, and XPF/exon 11 variant alleles in our control group were 0.41, 0.35, and 0.35, respectively. No significant association was observed between the variant alleles of XPD/exon 6 (OR=0.94, 95% CI=0.63-1.41), XPD/exon 23 (OR=1.24, 95% CI=0.82-1.86) and XPF/exon 11 (OR=1.08, 95% CI=0.72-1.64) and AD. Our results suggest that the polymorphic variants of these NER genes do not contribute to the risk of developing AD.

The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: the effect of heme oxygenase-1 on radiation enteritis.

BACKGROUND: Radiation enteritis is a significant clinical problem in patients receiving ionizing radiation directed at the abdomen or pelvis. The small intestine is the most radiosensitive gastrointestinal organ. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels of the small intestine were measured to determine the oxidative damage caused by radiation. In addition, caspase-3 activity of the small intestine was measured to define the degree of apoptosis. The present study was undertaken to investigate the effect of glutamine administration on heme oxygenase-1 (HO-1) expression of the radiation enteritis model. METHODS: Rats received 1 g/kg/d glutamine (HO-1-inducer) for 7 days before irradiation and continued for 3 days after irradiation. Zn-prothoporphyin (Zn-PP) 40 micromol/kg was delivered subcutaneously for 1 day before irradiation. Intestinal MPO activities and MDA levels are indicators of oxidative damage, whereas caspase-3 activities show the degree of apoptosis of the small intestine. At histopathologic examination, terminal ileum tissue was analyzed for morphologic changes. Also, the nuclear factor-kappa (NF-kappa) expression level of the terminal ileum was determined with immunohistochemistry methods to show the mucosal inflammatory process. RESULTS: Irradiation significantly increased the intestinal MPO and caspase-3 activities, MDA levels, and HO-1 expression in comparison with the sham group. Glutamine treatment was associated with increased HO-1 expression, decreased MPO activity, caspase-3 activity, and MDA levels. Inhibition of HO-1 activity by Zn-PP completely eliminated the protective effects of glutamine. Histopathologic examination showed that the intestinal mucosal structure was preserved in the glutamine-treated group. In the irradiation group, NF-kappaB overexpression was detected. NF-kappaB positivity was strongest in the intestine of animals in the radiation alone group and the Zn-PP-treated irradiation group. CONCLUSIONS: Glutamine appears to have protective effects against radiation-induced intestinal damage. This protective effect is mediated in part by the induction of HO-1 activity because inhibition of Zn-PP resulted in the complete abolishment of the protective effect of glutamine.

The efficacy of octreotide in pancreatic and intestinal changes: radiation-induced enteritis in animals.

Radiation enteritis occurs during the radiotherapy of many intraabdominal malignancies. Radiation induces cellular injury directly and through the generation of free radicals. In the present study we aimed to investigate the effect of octreotide (OCT) pretreatment in irradiation-induced enteritis. For this aim, rats were injected with 50 microg/kg OCT 4 days before irradiation and continued for 3 more days, until sacrifice. Then intestinal and pancreatic myeloperoxidase (MPO) activities and intestinal malondialdehyde (MDA) levels of the rats were measured. Irradiation significantly increased intestinal and pancreatic MPO activities and MDA levels of intestinal tissues in comparison to those of the sham group. OCT treatment improved this elevation. The histopathologic evaluation of the mucosal structure was also preserved in the OCT-treated group. Inflammation of pancreatic tissue was also confirmed with histopathological examinations. In the irradiation group, NFkappa-B overexpression was detected. OCT treatment decreased the end organ damage and inflammation of the small intestine. In conclusion, OCT appears to have beneficial effects on intestinal and pancreatic damage in abdominal irradiation through the inflammatory process.

The effect of heme oxygenase-1 induction by octreotide on radiation enteritis.

Radiation enteritis occurs as a response to abdominal radiation, which can cause mucosal damage in the gastrointestinal mucosal epithelium. The small intestine is one of the most radiosensitive organs in the abdomen. The present study was undertaken to investigate the effect of octreotide (OCT) administration on heme oxygenase-1 (HO-1) expression of the radiation enteritis model. Rats received 50 mg/kg/day OCT for 4 days before irradiation and continued for 3 days after irradiation. Intestinal myeloperoxidase (MPO) activities, malondialdehyde (MDA) levels are indicators of oxidative damage while caspase-3 activities reveal apoptosis degree of the small intestine. At histological examination, the terminal ileum tissue was analyzed for morphological changes. Irradiation significantly increased the intestinal MPO and caspase-3 activities, MDA levels and HO-1 expression in comparison to sham control group. OCT treatment was associated with increased HO-1 expression and caspase-3 activity, decreased MPO activity and MDA levels. Histological examination revealed that the intestinal mucosal structure was preserved in the OCT treated group. OCT appears to have protective effects against radiation-induced intestinal damage. This protective effect is, in part, mediated by modification of the inflammatory response and the induction of HO-1 expression.

The effect of glutamine on radiation-induced organ damage.

Radiation enteritis is a significant clinical problem in patients receiving ionizing radiation directed to the abdomen or pelvis. Although radiation is aimed to be directed against the malignant tissue, adjacent healthy tissues are also affected. The small intestine is the most sensitive organ to radiation. The present study was undertaken to investigate the possible protective effect of glutamine against radiation-induced intestinal, hepatic and pancreatic toxicity. Rats received 1 g/kg/day glutamine for seven days before irradiation and continued for three days after irradiation until sacrifice. Then intestinal, pancreatic and hepatic myeloperoxidase (MPO) activities, malondialdehyde (MDA) levels and caspase-3 activities of the sacrificed rats were measured. Irradiation significantly increased the intestinal and pancreatic MPO and caspase-3 activities and MDA levels in comparison to sham group. Glutamine treatment significantly decreased this elevation. Histopathological examination revealed that the intestinal mucosal structure was preserved and pancreatic inflammation decreased in the glutamine treated group. In irradiation group, NF-kappaB over expression was detected. There was no significant difference in histopathological and biochemical examinations of the liver between the groups. In conclusion, glutamine has beneficial effects on intestinal and pancreatic damage in abdominal irradiation through the inflammatory process and apoptosis.

The effect of taurine or betaine pretreatment on hepatotoxicity and prooxidant status induced by lipopolysaccharide treatment in the liver of rats.

BACKGROUND: Taurine or betaine have been reported to have antioxidative potential and inhibit Kupffer cell activation. These effects may play an important role in their hepatoprotective effects. Therefore, they may also have protective effects in lipopolysaccharide hepatotoxicity by both inhibiting Kupffer cell activation and behaving as antioxidants. DESIGN: The prophylactic efficiency of taurine or betaine pretreatment for the prevention of peroxidative changes induced by lipopolysaccharide treatment in the rat liver was investigated. METHODS: Lipopolysaccharide (10 mg/kg intraperitoneally) was given to rats pretreated with taurine (1.5%, w/v) or betaine (1.5%, w/v) in drinking water for 4 weeks and plasma transaminase activities as well as hepatic malondialdehyde, diene conjugate (DC), glutathione, alpha-tocopherol and ascorbic acid levels, and superoxide dismutase (SOD) and glutathione peroxidase activities were determined. RESULTS: Significant increases in plasma transaminase activities and hepatic malondialdehyde and DC levels and decreases in hepatic glutathione and alpha-tocopherol levels and SOD and glutathione peroxidase activities were observed 6 h after lipopolysaccharide treatment. This treatment did not alter ascorbic acid levels in the liver compared with controls. Taurine or betaine pretreatment in lipopolysaccharide-injected rats caused significant decreases in plasma transaminase activities and hepatic malondialdehyde and DC levels, and significant increases in glutathione and alpha-tocopherol (not betaine) levels without changing ascorbic acid levels and SOD and glutathione peroxidase activities in the liver. CONCLUSIONS: Our findings clearly indicate that taurine or betaine pretreatment was effective in the prevention of lipopolysaccharide-induced hepatotoxicity and prooxidant status.

Resistance of erythrocytes to lipid peroxidation in cirrhotic rats.

BACKGROUND: The aim of the present study was to investigate erythrocyte prooxidant-antioxidant balance in relation to liver and plasma lipid peroxidation in thioacetamide (TAA)-induced liver cirrhosis in rats. METHODS: Liver cirrhosis was produced by the administration of TAA (0.3 g/L of tap water) for a period of 3 months in rats. Serum, liver and erythrocyte lipid peroxide levels as well as liver glutathione (GSH) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined in cirrhotic rats. RESULTS: Hepatic cirrhosis was assessed by biochemical and histopathological findings. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and malondialdehyde (MDA) levels increased in cirrhotic rats. This treatment caused increased MDA and diene conjugate (DC) levels as well as decreased GSH levels and GSH-Px activities in the liver of cirrhotic rats. In these conditions, no significant changes in erythrocyte cholesterol, phospholipid levels as well as endogenous DC, and GSH levels and spontaneous hemolysis values were observed in erythrocytes of rats with TAA-induced liver cirrhosis. However, H(2)O(2)-induced MDA levels were detected to decrease significantly in erythrocytes of cirrhotic rats. CONCLUSIONS: Our results indicate that erythrocytes of TAA-induced cirrhotic rats have a resistance against peroxidative stress in contrast to the findings in plasma and liver.

Increased LDL+VLDL oxidizability and plasma homocysteine levels in chronic alcoholic patients.

The purpose of this study was to investigate the effect of heavy alcohol consumption on peroxidation status in apolipoprotein B-containing lipoproteins (LDL+VLDL) and plasma as well as plasma homocysteine (HC) levels in patients with chronic alcoholism who drank raki, a national Turkish beverage. For this reason, endogenous diene conjugate (DC) and lipid hydroperoxide (LOOH) levels and lag phase, maximum DC formation and propagation rate following copper induction were measured in apolipoprotein B-containing lipoproteins (LDL+VLDL) isolated by precipitation with dextrane sulfate and MgCl2 from plasma. In addition, serum malondialdehyde (MDA), DC, HC, folate and vitamin B12 levels as well as paraoxonase activity were determined. Serum MDA and DC levels were higher in heavy raki drinkers compared to control subjects. Significant increases in endogenous DC and LOOH levels in LDL+VLDL together with shortened lag phase were also observed in patients. In addition, HDL-cholesterol, HC and vitamin B12 levels and HDL-associated paraoxonase activity were found to be higher, but folate levels to be lower in serum of heavy raki consumers. In conclusion, our results indicate that increases in LDL+VLDL oxidizability and plasma HC levels may enhance the susceptibility to vascular diseases in heavy raki drinkers.

Peroxynitrite induced decrease in Na+, K+-ATPase activity is restored by taurine.

AIM: Peroxynitrite (ONOO-) is a powerful oxidant shown to damage membranes. In the present study, the effect of taurine on changes of liver plasma membrane Na+, K+-ATPase induced by ONOO- was investigated. METHODS: Liver plasma membrane was exposed to ONOO- with or without taurine. Na+, K+-ATPase activity and lipid peroxidation as thiobarbituric acid reactive substances (TBARS) levels were measured. RESULTS: Different concentrations of ONOO- (100, 200, 500, and 1000 micromol/L) were found to decrease liver plasma membrane Na+, K+-ATPase activity significantly. The depletion of enzyme activity was not concentration dependent. Effects of different concentrations of taurine on liver plasma membrane Na+, K+-ATPase activity were also measured. Taurine did not cause any increase in enzyme activity. When plasma membranes were treated with 200 micromol/L ONOO- with different concentrations of taurine, a restoring effect of taurine on enzyme activity was observed. TBARS levels were also measured and taurine was found to decrease the elevated values. CONCLUSION: Taurine is observed to act as an antioxidant of ONOO- to decrease lipid peroxidation and thus affect liver plasma membrane Na+, K+-ATPase by restoring its activity.

Induced oxidative stress and decreased expression of inducible heat shock protein 70 (ihsp 70) in patients with colorectal adenocarcinomas.

BACKGROUND: Colorectal cancer is one of the most common carcinomas observed in humans. Recently we have reported that increased oxidative stress is associated with human colorectal cancer. There are few and controversial studies on the clinical relevance of the expression of heat shock protein 70 (HSP 70), a member of the HSP family, in colorectal cancer. In this study, we assayed lipid peroxide levels, glutathione peroxidase (GPx) activity and the expression of inducible heat shock protein 70 (ihsp 70) in 20 paired samples of colorectal tumor and adjacent normal tissues in order to determine the relationship between oxidative stress and ihsp 70 expression. Histopathological results were also considered to establish the clinical relevance of ihsp 70 in colorectal cancer. METHODS: Malondialdehyde (MDA) levels as an indicator of lipid peroxidation and GPx activity were assayed by spectrophotometric methods. The Western blotting procedure was used for the determination of ihsp 70 expression. RESULTS: Significant increases were observed in MDA levels (111%) and GPx activities (50%) of malignant tissues as compared with normal tissues of the patients with colorectal cancer. The expression of ihsp 70 was found to be decreased in malignant tissues as compared with normal tissues of the patients. Significant negative correlations were detected between MDA levels and ihsp expression (r = -0.516; P < 0.05 ) and GPx activity and ihsp 70 expression (r = -0.471; P < 0.05) in malignant tissues of patients. When the patients were grouped according to histopathological characteristics, no difference was found in MDA levels, GPx activity and ihsp 70 expression. CONCLUSION: Our results indicate that ihsp70 expression is suppressed under induced oxidative stress conditions in malignant tissues of patients with colorectal cancer. Further research is needed to clarify the mechanisms responsible for this decrease and the definitive role of ihsp 70 in colorectal cancer.

Methionine supplementation did not augment oxidative stress, atherosclerotic changes and hepatotoxicity induced by high cholesterol diet in C57BL/6J mice.

The purpose of this study was to investigate the effect of a high-methionine plus cholesterol diet (HM+HC) on plasma, erythrocyte, liver and aorta lipid, lipid peroxide levels, and the liver antioxidant system, as well as hepatic and aortic histopathology in CS 7BL/6J mice, and to compare these results to those observed following administration of a high-methionine (HM) or high-cholesterol diet (HC) alone. Mice were fed diets containing 1.5% methionine, 1.5%, cholesterol and 0.5% cholic acid, or a combination of the two diets, for 4 mo. The HM diet did not alter cholesterol or diene conjugate (DC) levels in the plasma or aorta, but this diet caused increases in cholesterol, triglyceride, malondialdehyde (MDA) and DC levels and a decrease in a-tocopherol levels without any change in the levels of glutathione and ascorbic acid or the activities of superoxide dismutase, glutathione peroxidase and glutathione transferase in the liver of mice. However, the HC diet alone was found to further increase cholesterol, triglyceride. MDA and DC levels in the plasma and liver together with changes in hepatic antioxidant system elements, but aortic cholesterol and DC levels remained unchanged as compared to the control group. There were no changes in blood hemoglobin and erythrocyte MDA levels or erythrocyte hemolysis values in both the HM and HC groups. However, the parameters related to lipid and lipid peroxide and antioxidant systems did not change in the plasma or tissues of the HM+HC and HC groups. Only plasma cholesterol was observed to increase in the HM+HC group as compared to the HC group. In addition, histopathological findings in the liver and aorta were similar in the HC and HM+HC groups. In conclusion, our results indicate that the addition of methionine to the HC diet did not augment oxidative stress, hepatotoxicity or atherosclerotic changes induced by the HC diet in mice.

Hazelnut oil administration reduces aortic cholesterol accumulation and lipid peroxides in the plasma, liver, and aorta of rabbits fed a high-cholesterol diet.

Hazelnut oil (HO) is rich in monounsaturated fatty acids and antioxidants. We wanted to investigate the effect of HO on lipid levels and prooxidant-antioxidant status in rabbits fed a high-cholesterol (HC) diet. An HC diet caused significant increases in lipids and lipid peroxide levels in the plasma, liver, and aorta together with histopathological atherosclerotic changes in the aorta. Glutathione levels, glutathione peroxidase, and glutathione transferase activities decreased significantly, but superoxide dismutase activity and vitamin E and C levels remained unchanged in the livers of rabbits following HC diet. HO supplementation reduced plasma, liver, and aorta lipid peroxide levels and aorta cholesterol levels together with amelioration in atherosclerotic lesions in the aortas of rabbits fed an HC diet, without any decreasing effect on cholesterol levels in the plasma or liver. HO did not alter the antioxidant system in the liver in the HC group. Our findings indicate that HO reduced oxidative stress and cholesterol accumulation in the aortas of rabbits fed an HC diet.