No abstract

The mechanisms of liver injury from cold storage and reperfusion are not completely understood. The aim of the present study was to investigate: 1) whether the inactivation of Kupffer cells (KCs) by gadolinium chloride (GadCl) modulates cold ischemia-reperfusion injury of rat liver; and 2) whether cold storage of rat liver involves injury to biliary epithelial cells (BECs). Hepatobiliary function was assessed using an isolated perfused rat liver model. Compared with control livers, in livers subjected to cold storage at 4 degrees C in Euro-Collins solution (EC) for 18 hours or in University of Wisconsin solution (UW) for 48 hours, portal flow was lower and resistance significantly higher, taurocholate (TC) and bromosulfophthalein (BSP) elimination were markedly impaired, bile flow was reduced, and lactate dehydrogenase (LDH) leakage into the perfusate was increased. Pretreatment of rats with GadCl, a selective KC toxicant, abrogated disturbances of the microcirculation in both models, but it did not influence viability and functional parameters of the liver. Most of the parameters studied in livers stored in UW solution for 18 hours were not significantly different from those found in control livers. As to biliary activity of gamma-glutamyl transferase (GGT), as an index of BEC integrity, it was increased with increasing time of cold storage. The reabsorption of glucose from the bile decreased with longer storage time. The results suggest the following: 1) that cold ischemia-reperfusion injury of rat liver is mediated by KC-dependent (hepatic microcirculation) and -independent (parenchymal cell function) mechanisms; and 2) that cold storage of rat liver induces functional impairment of BECs.

The oxidation of low-density lipoproteins (LDL) and high-density lipoproteins (HDL) and fatty acid composition, which may affect the resistance of lipoproteins to oxidation, were determined in 24 lacto-ovo vegetarians. Vegetarian diets contain more essential polyunsaturated fatty acids (PUFAs). Therefore, the relationship between LDL and HDL oxidation resistance measured by the kinetics of the formation of fatty acid conjugated dienes (lag time, maximal rate of oxidation and maximal amount of conjugated dienes), LDL and HDL fatty acid composition and vitamin E content were evaluated. All parameters of in vitro oxidation were significantly lower in HDL when compared with LDL. The relative values of arachidonic, dihomo-γ-linoleic and docosahexaenoic acid were significantly higher in HDL, α-linolenic acid content significantly lower, when compared with LDL; the peroxidizability index was significantly higher in HDL. The content of vitamin E was found more than 2-fold lower in HDL particles. The results show the importance of fatty acid composition in the resistance of LDL and HDL to oxidation and from this aspect, the composition of LDL isolated from vegetarians seems to be more favourable compared to HDL.

Vegetarian food with a higher content of natural antioxidants may decrease the risk of developing cardiovascular diseases. The oxidative modification of low-density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis. The objectives of this study were to investigate in vitro resistance of LDL against oxidation and antioxidative status of plasma in 19 lactoovovegetarians and nonvegetarians (n = 19). The kinetics of conjugated diene formation (lag time and maximal rate of oxidation, V_max) and thiobarbituric acid reacting substances (TBARS) were determined as indices of LDL oxidation. No significant differences in lag time and V_max were observed between vegetarians and nonvegetarians, while TBARS in native and oxidatively modified LDL were significantly lower in vegetarians. Plasma vitamin (C, E, β-carotene) levels were increased in vegetarians, but only the vitamin C increase was statistically significant. Vegetarians also had a significantly increased plasma total antioxidant status (TAS) and molar ratio vitamin E/cholesterol which indicates a more effective protection of lipoproteins against oxidation. A significant positive correlation was observed between lag time and plasma TAS in both vegetarians and nonvegetarians. We conclude that although the resistance of LDL to in vitro oxidation, as measured by the kinetics of conjugated diene formation was not altered in vegetarians, the effect of vegetarian nutritional habits favorably affected TBARS levels in LDL and total plasma antioxidant capacity.

The effect of ciprofibrate therapy on plasma lipids and lipoproteins, HDL and LDL subfraction profile, fractional esterification rate of HDL cholesterol (FER(HDL)) and the resistance of LDL and serum lipids to oxidation was studied in 24 males with type 2 diabetes and atherogenic lipoprotein phenotype (ALP). We also examined the effect of ciprofibrate therapy on oxidative DNA damage in peripheral lymphocytes. No differences in glucose, HbA1C and BMI levels were found after three months of ciprofibrate therapy. Ciprofibrate significantly decreased total cholesterol and triglyceride levels by 5.5% and 50% (p = 0.05; 0.001, respectively) and increased HDL-cholesterol levels by 8.5% (p = 0.05). FER(HDL) and LDL subfraction profile were also favorably affected. However, no effect on HDL subclasses was found. There were no statistically significant differences in lipid resistance to oxidation measured in serum and in LDL (lag time and Vmax) before and after therapy. No significant effect of ciprofibrate was found on oxidative DNA damage. The evaluation of the relationship between oxidative damage of purines with lag time in LDL and maximal rate of serum lipid oxidation showed significant correlations after therapy (r = -0.58; 0.47, p = 0.01; 0.05, respectively), but only trends before starting ciprofibrate treatment. Type 2 diabetes mellitus represents a complex metabolic disorder expressed in glucose and lipoprotein disturbances and increased oxidative stress. Ciprofibrate therapy favorably affected major features of lipid abnormalities of diabetic patients, but the level of oxidative stress assessed by in vitro and in vivo methods was not changed. The evaluation of expected logical correlations between the parameters of lipoprotein metabolism, lipid resistance in serum and LDL, and oxidative DNA damage showed that those correlations were more relevant and significant after ciprofibrate treatment and were not related with glucose homeostasis.