The influence of vitamin-rich diet on the extent of lipoperoxidation in brain of mice during an acute post-insulin hypoglycaemia.

Antioxidatives are widely used and recommended in common clinical praxis, even though they may have negative impact on our health under some circumstances (i.e. N-acetylcysteine, vitamin E, risk of lung cancer etc.). Our aim was to evaluate the role of exogenous scavengers in prevention of induced oxidative stress in rodents. Male ICR mice were used and acute hypoglycaemia was induced with insulin. The mice were randomized into eight experimental groups, either pretreated by vitamin C or vitamin E or combinations with respective vehicles. Total malondialdehyde (MDA), superoxide dismutase (SOD), and selenium-dependent glutathione peroxidase (GSHPx) activity were measured in brain tissue samples. ANOVA with a post-hoc Duncan or Turkey׳s tests were used for statistical evaluation. A statistically significant increase in brain MDA was observed after insulin-induced severe hypoglycaemia relative to normoglycaemia. Animals pretreated with vitamins, both in monotherapy and in combination (both P<0.05), had significantly lower MDA values compared with animals without pretreatment. Importantly, significant differences were also observed after combination of vitamin C and E in GSHPx and SOD (both P<0.05).

Iron stores are associated with asymptomatic atherosclerosis in healthy men of primary prevention.

BACKGROUND: The aim of our study was to assess the impact of increased iron stores on the presence of asymptomatic atherosclerosis in a cohort of healthy men. We anticipated that higher iron stores would be associated with higher soluble cluster of differentiation 163 (sCD163) concentrations, elevated markers of oxidative stress, inflammation and higher common carotid intima-media thickness, independently of traditional risk factors of atherosclerosis. METHODS: In this cross-sectional study that included 72 healthy men, we measured the ultrasonography of common carotid intima-media thickness (IACC), the ratio of plasma-circulating transferrin receptors concentration to plasma ferritin concentration, certain inflammatory and oxidative stress markers, insulin sensitivity, plasma lipids and markers of endothelial dysfunction. RESULTS: The plasma-circulating transferrin receptor concentration to plasma ferritin concentration ratio (TfR/F) showed significant association with IACC (r=-0·310, P=0·008 vs. r=0·295, P=0·012). Multivariate analysis confirmed that the correlation of TfR/F with IACC is independent of traditional risk factors of atherosclerosis. The TfR/F ratio correlated with other indicators of atherosclerotic process fibrinogen (r=-0·292, P=0·013), von Willebrand factor (vWf; r=0·284, P=0·017), sCD163 (r=0·239, P=0·043) and IL-8 (r=0·233, P=0·049). In multivariate analysis, TfR/F independently correlated with haemoglobin (ß=-0·220, P=0·047), fibrinogen (ß=-0·290, P=0·009), IL-8 (ß=0·227, P=0·039) and sCD163 (ß=0·244, P=0·025); however, when vWf was added, significant independent correlation was seen only with fibrinogen (ß=-0·301, P=0·007) and IL-8 (ß=0·219, P=0·047). In addition, we demonstrated the independent correlation of sCD163 with vWf (ß=0·240, P=0·040). CONCLUSIONS: Our study showed a clear association of body iron stores expressed by the TfR/F ratio with asymptomatic carotid atherosclerosis. TfR/F further exhibited an independent positive correlation with fibrinogen and a negative correlation with sCD163 and IL-8.

Relationship between increased body iron stores, oxidative stress and insulin resistance in healthy men.

AIM: The aim of our cross-sectional study was to assess the relationships between body iron stores, oxidative stress, impaired insulin sensitivity and carotid atherosclerosis in a cohort of healthy men in primary prevention of cardiovascular disease. METHODS: We examined 151 volunteers, aged 35- 60 years. Anthropometric parameters, markers of metabolic syndrome, insulin resistance, inflammatory markers, parameters of oxidative stress and intima-media thickness of common carotid artery were measured. RESULTS: Ferritin correlated positively with waist circumference, body mass index, impaired insulin sensitivity, plasma triglycerides and inversely with high-density lipoprotein cholesterol. We observed positive correlations between ferritin, oxidized lowdensity lipoprotein and advanced oxidation protein products after adjustment for age, waist circumference, body mass index and measured inflammatory markers (high-sensitivity C-reactive protein, fibrinogen, interleukin-6 and tumor necrosis factor-alpha). There were no significant associations between ferritin and intima-media thickness or markers of endothelial dysfunction. In a stepwise multiple regression analysis, triglycerides, waist circumference and elevated transaminases were independent determinants of the serum ferritin level. CONCLUSION: Our results provide evidence for a relationship between plasma ferritin and oxidative modification of lipids as well as proteins in vivo. Higher body iron stores may contribute to impaired insulin sensitivity through increased oxidative stress in a cohort of healthy men.

Effect of two different UVA doses on the rabbit cornea and lens.

The aim of the present paper was to examine the irradiation effect of two doses of UVA rays (365 nm) on the rabbit cornea and lens. Corneas of anesthetized adult albino rabbits were irradiated with UVA rays for 5 days (daily dose 1.01 J cm(-2) in one group of rabbits and daily dose 2.02 J cm(-2) in the second group of animals). The third day after the last irradiation, the rabbits were killed, and their eyes were employed for spectrophotometrical, biochemical and immunohistochemical investigations. Normal eyes served as controls. Absorption spectra of the whole corneal centers were recorded over the UV-VIS (visible) spectral range. Levels of antioxidant and prooxidant enzymes, nitric oxide synthases and nitric oxide (indirectly measured as nitrate concentration) were investigated in the cornea. Malondialdehyde, a byproduct of lipid peroxidation, was examined in the cornea and lens. The results show that the staining for endothelial nitric oxide synthase was more pronounced in corneas irradiated with the higher UVA dose. Otherwise, UVA rays at either dose did not significantly change corneal light absorption properties and did not cause statistically significant metabolic changes in the cornea or lens. In conclusion, UVA rays at the employed doses did not evoke harmful effects in the cornea or lens.

Influence of losartan and enalapril on urinary excretion of 8-isoprostane in experimental nephrotic syndrome.

BACKGROUND: The increased permeability of the glomerular capillary wall in adriamycin nephropathy may be mediated by increased generation of free radicals, possibly also by the non-enzymatic production of isoprostanes induced by oxidative stress. ACE inhibitors and angiotensin II antagonists may reduce proteinuria, perhaps by decreasing intraglomerular pressure and increasing the selective permeabiity of the glomerular capillary wall. MATERIAL/METHODS: We compared the effect of an ACE inhibitor, enalapril, and an angiotensin II antagonist, losartan, on total malodialdehyde in blood and the urinary excretion of certain eicosanoids and their metabolites (TxB(2), 6-keto-PGF(1alpha), bicyclo-PGE(2) and 8-isoprostane) in experimental adriamycin-induced nephrotic syndrome in rats. RESULTS: Increased proteinuria in adriamycin-treated rats was not prevented by losartan, but tended to be partly mitigated by enalapril. However, both losartan and enalapril prevented the adriamycin-induced increase of total MDA in serum, but urinary excretion of 8-isoprostane was increased in nephrotic rats treated by losartan compared to controls. The enalapril-induced increase in urinary excretion of bicyclo-PGE(2) was possibly mediated by kinins. Proteinuria positively correlated with urinary excretion of 8-isoprostane, and proteinuric rats also had a significantly higher urinary excretion of 8-isoprostane than non-proteinuric rats. CONCLUSIONS: Proteinuria in the acute phase of adriamycine nephropathy may be dependent on free radical generation and the formation of 8-isoprostane. The mild antiproteinuric effect of enalapril, but not losartan, may suggest the contributory role of the inhibition of kinin degradation in the antiproteinuric action of enalapril in this model of nephrotic syndrome.