Ümit Mutlu-Türkoğlu

Age-related increases in plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in elderly subjects

OBJECTIVES Increased oxidative stress has been hypothesized to play an important role in the aging process. A role for oxidative damage in normal aging is supported by studies in experimental animals, but there is limited evidence in humans. To investigate the relationship between the oxidative stress and aging in humans, we determined lipid and protein oxidation in plasma as well as DNA damage in lymphocytes in young and elderly subjects. DESIGN AND METHODS 55 healthy subjects were divided into young (21-40 years) and elderly (61-85 years) groups. Plasma malondialdehyde (MDA), protein carbonyl (PC) levels, and grade of DNA damage in lymphocytes using comet assay as well as total ferric reducing antioxidant power (FRAP) in plasma were determined in young and elderly subjects. RESULTS Plasma MDA and PC levels were found to be increased in plasma of elderly subjects as compared to young subjects. Increases in endogenous and H2O2-induced DNA damage were also observed in lymphocytes of elderly subjects. In addition, we detected a significant decrease in FRAP values in elderly subjects. Plasma MDA, PC levels and endogenous and H2O2-induced DNA damage were positively correlated with aging, but negatively with FRAP values. CONCLUSION We evaluated MDA, PC levels and lymphocyte DNA damage altogether in both young and elderly subjects for the first time. The results of this study strongly support the presence of increased oxidative stress in elderly subjects.

An increase in lipoprotein oxidation and endogenous lipid peroxides in serum of obese women.

Abstract. Endogenous malondialdehyde and diene conjugate levels, the susceptibility of apolipoprotein B-containing lipoproteins to copper-induced lipid peroxidation, and antibody titer against oxidized low-density lipoproteins were increased, but serum antioxidant activity was unchanged in obese women. Serum cholesterol, low-density lipoproteincholesterol, and trigliceride levels were also elevated, but high-density lipoprotein-cholesterol levels remained unchanged in obese women. In vitro, oxidation of apolipoprotein B-containing lipoproteins and levels of antibody against oxidized low-density lipoprotein correlated with body mass index, serum total cholesterol, and low-density lipoproteincholesterol levels in obese women. These results indicate that obesity is associated with increases in endogenous lipid peroxides, oxidation of low-density lipoproteins, and lipids in serum.

Do Vitamin E and Selenium Have Beneficial Effects on Trinitrobenzenesulfonic Acid-Induced Experimental Colitis

The balance between oxidant and antioxidant systems may be important in the pathogenesis and/or maintenance of tissue injury in ulcerative colitis. This study was designed to evaluate the effects of vitamin E and selenium supplementations on tissue injury and oxidative stress in trinitrobenzenesulfonic acid-induced ulcerative colitis in rats. Trinitrobenzenesulfonic acid administration severely changed the normal architecture of the colon and significantly increased the levels of malondialdehyde, protein carbonyl, and xantine oxidase (P < 0.001) in the colon homogenates of these rats. Supplementation of selenium to the trinitrobenzenesulfonic acid-treated rats neither improved the histopathological findings nor decreased the levels of malondialdehyde and protein carbonyl. Vitamin E supplementation reduced the levels of malondialdehyde and protein carbonyl but did not improve the colonic lesions. Supplementation of vitamin E+selenium significantly reduced both the severity of colonic lesions and the levels of malondialdehyde and protein carbonyl. In conclusion, we suggest that antioxidants and specific micronutrients may have beneficial effects in the treatment of ulcerative colitis.

Increased lipid peroxidation in serum and low-density lipoproteins associated with aging in humans.

This study was carried out in 140 healthy subjects who were divided into three subgroups of age: young (21-40 years), mature (41-60 years), and elderly (61-85 years) to investigate lipid peroxides and the antioxidant system in serum and low-density lipoproteins (LDL). Serum levels of cholesterol and LDL-cholesterol increased with age. The elderly group was found to have higher polyunsaturated fatty acid (PUFA) levels, thiobarbituric acid reactive substances (TBARS), diene conjugates, and lower cholesterol-adjusted vitamin E levels and antioxidant activity (AOA) as compared to the young group. No age-related difference was detected in serum vitamin C levels. Age correlated positively with serum cholesterol, LDL-cholesterol, PUFA, TBARS, diene conjugates, and negatively with cholesterol-adjusted vitamin E levels and AOA. In addition, endogenous LDL diene conjugate levels and the susceptibility of LDL to copper-induced lipid peroxidation increased in elderly subjects as compared with young subjects. In addition, positive correlations were detected between age and LDL endogenous diene conjugate levels and TBARS formation after copper incubation. However, the susceptibility of whole serum to copper-induced lipid peroxidation did not change in young and elderly subjects. Our results show that endogenous lipid peroxide levels in serum and LDL, and the susceptibility of LDL to copper-induced oxidation, increased with aging in humans.

Glutathione S-transferase-pi in malignant tissues and plasma of human colorectal and gastric cancers.

Abstract. Purpose: In this study, 16 paired samples of colorectal and gastric cancers and adjacent non-neoplastic tissues were analysed for the determination of glutathione S-transferase (GST) activities and the expression of GST-pi. Methods: Western blotting procedure as well as plasma GST-pi levels were used. Results: GST activities were found to be increased in malignant tissues of patient compared with adjacent normal tissues. A significant correlation was detected between GST activity and GST-pi expression in malignant tissues of patients. Plasma GST-pi levels increased in patients compared to aged-matched control subjects. When the patients were grouped according to TNM stage, GST-pi expression in malignant tissues as well as plasma GST-pi levels were higher in patients with more advanced tumor stages. Conclusions: Our results indicate that GST-pi expression in malignant tissues and plasma GST-pi levels in human colorectal and gastric cancers increased depending on the stages of tumor.

Cholesteryl Ester Transfer Protein Taq1B Polymorphism in an Angiographically Assessed Turkish Population: No Effects on Coronary Artery Disease Risk

BACKGROUND Taq1B polymorphism of cholesteryl ester transfer protein (CETP) is believed to associate with high-density lipoprotein-cholesterol (HDL-C) levels and may alter the susceptibility to atherosclerosis. AIM OF THE STUDY This study investigated the effects of Taq1B polymorphism on HDL-C and coronary artery disease (CAD) risk in angiographically defined CAD patients. METHODS One hundred thirty-five CAD patients and 112 healthy controls were screened for the CETP Taq1B genotype and plasma lipids. RESULTS The genotype frequency of CAD patients and controls were similar. The HDL-C levels of all genotypes in the CAD group were significantly lower than the corresponding controls. Smoking and plasma triglycerides were the predictors of the HDL-C level in B1B1 bearers, whereas the subjects with a polymorphic B2 allele were affected by smoking and sex. CONCLUSION CETP Taq1B polymorphism neither plays a role in determining HDL-C levels nor is a useful predictor of the risk of CAD.

The role of stimulated lipid peroxidation and impaired calcium sequestration in the enhancement of cocaine induced hepatotoxicity by ethanol

The purpose of this study was to investigate possible mechanism of cocaine-induced hepatotoxicity and its potentiation by ethanol in mice. Ethanol (2 g/kg) and/or cocaine (25 mg/kg) injections were given as binge model (five injections in 3 days). Cocaine administration with or without ethanol caused an increase in lipid peroxidation in liver homogenate and its subcellular fractions. The greatest increases were observed in mitochondrial fraction following cocaine plus ethanol treatment. Also, glutathione (GSH) levels were increased in liver homogenate and its mitochondrial fractions after cocaine and cocaine plus ethanol treatment. Microsomal calcium sequestration was found to decrease in all treatments. These results suggest that increased lipid peroxidation and decreased microsomal calcium sequestration in the liver may play a possible role cocaine-induced hepatotoxicity and its potentiation by ethanol.

Association of cholesteryl ester transfer protein -629C > a polymorphism with high-density lipoprotein cholesterol levels in coronary artery disease patients.

In Turkish population, plasma HDL‐C levels were found to be lower than in any other country and it is suggested that this is associated with genetic origin. The cholesteryl ester transfer protein (CETP) −629C > A polymorphism is associated with lower plasma CETP concentration, with increased HDL‐C level. In the present study, the frequency of −629C > A polymorphism in patients with coronary artery disease (CAD) was investigated and the effect of genotype on HDL‐C was evaluated in a Turkish population. For this aim CETP −629C > A polymorphism was studied in angiographically documented CAD patients and healthy controls.