Effect of intake of exogenous vitamins C, E and beta-carotene on the antioxidative status in kidneys of rats with streptozotocin-induced diabetes.

We studied the effect of supplementation with vitamins C, E and beta-carotene (PARABION, produced by Syndipharma) on antioxidative status in kidneys of male Wistar rats with diabetes induced by intravenous application of streptozotocin (45 mg.kg-1 of body weight). The animals received subtherapeutic doses of Insulin Interdep (6 U.kg-1 of body weight). A significant decrease of malondialdehyde (MDA), reduced (GSH) and oxidized (GSSG) glutathione and reduction of the activities of Se-glutathione peroxidase (Se-GSH-PX, EC. 1.11.1.9.) and glutathione S-transferase (GST, EC. 2.5.1.18.) were observed in kidneys of diabetic rats treated with these vitamins. On the contrary, the activity of CuZn-superoxide dismutase (CuZn-SOD, EC. 1.15.1.1) and the level of vitamin C (vit. C) increased significantly. No changes were observed for vitamin E (vit. E), beta-carotene and catalase (CAT, EC. 1.11.1.6). Supplementation with vitamins C, E and beta-carotene resulted in an improvement of antioxidative status of kidneys of rats with streptozotocin-induced diabetes.

The effect of dietary protein and sucrose on the diabetic rat kidney.

The effect of 3 months feeding with diets of different protein and sucrose content (9% casein + 70% sucrose vs. 18% casein + 61% sucrose) on the development of diabetic nephropathy and changes in serum lipid spectrum was investigated in rats with insulin-dependent diabetes (streptozotocin 45 mg.kg-1). Metabolism of diabetic animals (before the nutritional regimen) was characterized by hyperglycaemia, moderate hyperlipidemia, lipid accumulation in the liver and elevated creatinine concentration in the blood. Kidney weight and protein content were not significantly changed. Histological picture of kidneys showed initial changes of glomerular structure. After three months hyperlipoproteinaemia was more accentuated in animals given either of the two diets, the kidneys were hypertrophic with a higher protein content and displayed morphological changes of diabetic nephropathy. Animals given the low-protein diet developed smaller morphological changes both in glomeruli and tubuli. The study indicates that dietary protein and not hyperlipoproteinaemia is the major factor, which may significantly influence the progress of diabetic nephropathy.

Antioxidative state of the myocardium and kidneys in acute diabetic rats.

The influence of acute diabetes (8 days), induced by streptozotocin (45 mg.kg-1 body weight) on myocardial and renal antioxidative conditions was investigated. The animals were given subtherapeutical doses of insulin (Interdep 6 U. kg-1 body weight, s.c.). Considerably increased levels of malondialdehyde (MDA), as well as of superoxide dismutase (SOD) and catalase (CAT) activity were found in the myocardium of diabetic animals. The oxidized glutathione (GSSG) level and glutathione peroxidase (GSH-PX) activity remained unchanged. The reduced glutathione (GSH) level as well as the activity of glutathione S-transferase (GST) were significantly lower. The activity of GSH-PX in the kidneys of diabetic rats increased by 60% and that of GST by 105%, respectively. CAT and SOD activity values were unchanged.

The influence of tolbutamide on fatty acid metabolism in the liver and muscle.

Metabolism of palmitate-14C was studied in the rat liver and muscle incubated with 1 mmol.l-1 tolbutamide in vitro experiments: Tolbutamide reduces the utilization of free fatty acids in the liver by inhibiting their uptake, incorporation into total lipids, and oxidation to 14CO2. Tolbutamide stimulates the incorporation into the triacylglycerol fraction in individual liver lipid fractions and inhibits the incorporation into the free fatty acid fraction. As in the liver, tolbutamide inhibits the uptake, incorporation into total lipids, and oxidation to 14CO2 in the muscle. In individual lipid fractions, tolbutamide only inhibits the incorporation of palmitate into cholesterol esters. It can be concluded that tolbutamide directly interferes with fatty acid metabolism and thus improves glucose utilization and insulin resistance.

Effect of the oyster fungus on glycaemia and cholesterolaemia in rats with insulin-dependent diabetes.

We have investigated the effect of a diet containing of 4% oyster fungus (Pleurotus ostreatus) and 0.1% cholesterol on glycaemia and hyperlipoproteinaemia in rats with insulin-dependent diabetes (streptozotocin 45 mg/kg). After two months, the rats with diabetes kept on the oyster fungus diet, had a significantly lower basal and postprandial glycaemia, the insulinaemia remained unchanged. The cholesterol concentration was decreased by more than 40%, the lipoprotein profile was upgraded by the decrease of the cholesterol in both the low density and very low density lipoproteins. The oyster fungus decreased the cholesterol accumulation in the liver and had no significant effects on the levels of serum and liver triacylglycerols.

Effect of the oyster fungus on glycaemia and cholesterolaemia in rats with insulin-dependent diabetes.

We have investigated the effect of a diet containing of 4% oyster fungus (Pleurotus ostreatus) and 0.1% cholesterol on glycaemia and hyperlipoproteinaemia in rats with insulin-dependent diabetes (streptozotocin 45 mg/kg). After two months, the rats with diabetes kept on the oyster fungus diet, had a significantly lower basal and postprandial glycaemia, the insulinaemia remained unchanged. The cholesterol concentration was decreased by more than 40%, the lipoprotein profile was upgraded by the decrease of the cholesterol in both the low density and very low density lipoproteins. The oyster fungus decreased the cholesterol accumulation in the liver and had no significant effects on the levels of serum and liver triacylglycerols.

[Obesity and hyperlipoproteinemia. I. Changes in lipid levels in obese persons]. / Obezita a hyperlipoproteinémia. I. Zmeny hladín lipidov v krvi obéznych osôb.

The authors investigated changes in serum lipid levels in 115 obese men and 172 obese women. The body mass index (BMI) of the subjects was 29-50 kg/m2. The group was subdivided by sex and age as follows: 15-18 years, 19-25 years, 26-35 years, 36-55 years. It was revealed that with advancing age and increasing body weight the mean tiacylglycerol levels in men increased from 1.74 mmol/l to 4.40 mmol/l, in women from 1.37 mmol/l to 1.84 mmol/l. The mean levels of total serum cholesterol increased in men from 4.58 mmol/l to 6.82 mmol/l, in women from 5.09 mmol/l to 5.96 mmol/l. In the rise of serum cholesterol in men the LDL and VLDL fractions participated, in women mainly the LDL fraction. Conversely the HDL fraction declined in men from 1.60 mmol/l to 1.20 mmol/l, in women from 1.71 mmol/l to 1.26 mmol/l. The mean value of the atherogenic index in men increased from 2.88 to 5.68, in women from 2.99 to 4.73. The results indicate the adverse changes of serum lipid levels in obese subjects which appear in men already after the age of 25 years, in women 10-20 years later. The authors discuss the causes of hyperlipoproteinaemia and the risk of atherosclerosis in obesity.

[Obesity and hyperlipoproteinemia. II. The effect of a low energy diet on lipid levels in the blood of obese persons]. / Obezita a hyperlipoproteinémia. II. Vplyv nízkoenergetickej diéty na hladiny lipidov v krvi obéznych osôb.

In 287 obese men and women with BMI values of 29-50 kg/m2, divided by sex and age, the effect of a low-energy diet on triacylglycerol (TG), total cholesterol (TC) and HDL-cholesterol (HDL-C) serum levels was investigated. On a diet of 2500 kJ/day (4 weeks) and 4000-7000 kJ/day (6 weeks) the body weight declined by 10-11% from the initial value. There was a significant drop of TG in obese men above 25 years and in obese women above 35 years of age. The mean TC values did not change significantly after weight reduction. The mean HDL-C levels increased significantly after weight reduction, as compared with initial values in both sexes in the groups aged 26-35 years. In this group there was also an increase of the relative ratio of HDL-C in TC and the value of the atherogenic index declined. The authors draw attention to the fact that with regard to preserving normal blood lipid levels, in particular in obese men, it is necessary to reduce or normalize body weight in the course of the third decade.

Effect of hippurate on tissue fatty acid metabolism.

The authors studied 1-14C-palmitate metabolism in rat muscle, renal cortex and liver incubated with synthetic hippurate in vitro (1 mmol/l). a) Hippurate did not affect 1-14C-palmitate uptake and utilization in the muscle (hemidiaphragm). b) In the renal cortex it stimulated only the incorporation into total lipids and from the individual lipid fractions into mono- and diglycerides and free fatty acids (FFA). c) In the liver it stimulated the uptake, oxidation to 14CO2 and incorporation into total lipids and, out of the individual lipid fractions, into phospholipids, triacylglycerols and free fatty acids. d) Hippurate already had a significant effect in the concentration of 0.5 mmol/l, i.e. during the development of the disturbance and not just as a supplementary factor in advanced renal insufficiency. It is concluded that, by interfering with fatty acid metabolism, the hippurate present in the serum of patients with renal insufficiency plays an active role in the development of dyslipoproteinaemia in such patients.

Effect of pectin on cholesterol distribution in the lipoproteins of streptozotocin-diabetic rats fed cholesterol diet.

In rats fed a semisynthetic diet, streptozotocin-induced diabetes [45 mg/kg, 17 days] led to hypertriglyceridaemia [6.4 mmol/l], to a marked increase in the proportion of plasma cholesterol present in the very low density lipoproteins [VLDL] [to 40 %] and to a decrease in the amount present in the high density lipoproteins [HDL] [to 34 %]. The addition of 0.25 % cholesterol to the above diet led in healthy rats to hypercholesterolaemia [4.3 mmol/l] and to similar changes in the distribution of cholesterol in the lipoproteins. In diabetic rats, the same diet led to pronounced hypertriglyceridaemia [13.8 mmol/l] and hypercholesterolaemia [18.9 mmol/l], while the proportion of HDL-borne plasma cholesterol fell still further to 6 % and rose in the VLDL to 70 %. The addition of pectin to the diet in 6 % concentration markedly inhibited triglyceridaemia [3.3 mmol/l] and cholesterolaemia [4.4 mmol/l] and raised the proportion of HDL plasma cholesterol to 47 %.

The fatty acid composition of the tissues of streptozotocin-diabetic rats.

The authors studied acute changes in the fatty acid composition of the tissues of streptozotocin-diabetic rats. They found that streptozotocin diabetes led to changes in the total lipids fatty acid spectrum in serum and in tissues (liver, adipose tissue, renal cortex diaphragm). After only 7 days' diabetes there was an increase in the percentual proportion of saturated fatty acids and a decrease in the amount of polyene fatty acids in the serum and in all the above tissue of diabetic animals. Palmitic acid (16:0) participated in the increase in the proportion of saturated fatty acids in all the given tissues, while stearic acid (18:0) played a role in the increase in the renal cortex and the serum. Among the monoene acids, there was a drop in the proportion of palmitoleic acid (16:1) in the adipose tissue and serum and in the amount of oleic acid (18:1) in the renal cortex, liver and muscle. Linoleic acid (18:2) played a role in the decrease in the proportion of polyene acids in all the given tissues and the serum, while arachidonic acid (20:4) was involved in the drop in the renal cortex, liver and muscle. The results show that diabetes leads to changes in the fatty acid composition of the renal cortex and muscle, as well as of the liver and adipose tissue. At present it is not yet clear whether there is an absolute decrease in the proportion of essential fatty acids, or whether diabetes is characterized by an increase in the amount of lipids in both serum and tissues.

Kinetics of plasma triglycerides in rats with streptozotocin diabetes.

Streptozotocin diabetes [45 mg/kg] in rats fed on a standard diet, with insulin substitutional therapy - 66 [nkat/kg]/d [[4 U/kg b.w.]d] for the first 3 days - led during an 8 days' experiment to marked hypertriglyceridaemia [4.86 mmol/l] and to triglyceride accumulation in the liver [22.35 mmol/kg]. The endogenous triglyceride secretion rate, studied by means of a Triton WR 1339 block of lipoprotein lipase, was almost 30 % lower in diabetic rats. The half-time of plasma 14C-triglycerides [labelled endogenously with 14C-1-palmitic acid] almost doubled and the fractional turnover rate fell to half the value in the control animals. Hypertriglyceridaemia in diabetic rats [60 % insulin deficiency] is caused by slower removal of lipoprotein triglycerides from the plasma space, owing to reduced lipolytic activity in the peripheral tissues.

Metabolism of palmitate-1-14C in the tissues of rats with streptozotocin diabetes.

The authors studied palmitate-1-14C metabolism in the tissues of rats with streptozotocin diabetes characterized by hyperglycaemia, hypoinsulinaemia and hyperlipaemia. In the tissues of diabetic animals the following changes were found in the uptake and utilization of free fatty acids: 1. In adipose tissue, FFA uptake and incorporation into the total adipose tissue lipids and into the FFA, TG, MG and DG, Pl and CHE fractions diminished. Oxidation to 14CO2 increased. 2. In the liver, FFA uptake and incorporation into the total liver lipids and into the FFA, TG, MG and DG, Pl and CHE fractions increased. Oxidation to 14CO2 remained unchanged. 3. In the diaphragm, FFA uptake and incorporation into the total tissue lipids and into the various lipids fractions (FFA, TG, MG and DG, CHE, Pl) rose. Oxidation to 14CO2 also rose. 4. The kidney displayed no changes in FFA metabolism from any of the metabolic aspects studied. The authors conclude that diabetes, in various tissues, causes changes in FFA metabolism which are unrelated to changes in the adipose tissue and which participate in the resultant lipid levels in the blood.

[Fat and nitrogen balances after jejunoileal bypass for obesity (author's transl)]. / Fett- und Sticksoffbilanz nach jejunoilealem Bypass bei Adipositas.

Seventy-five patients after jejunoileal bypass for morbid obesity were investigated. The body weight, fat and nitrogen balances were followed. In the second year after operation the stabilization of body weight was observed. The fecal fat excretion was average one third of the ingested amount of fat and the fecal nitrogen loss was twice or three-times higher than normal value. In the first year after operation in many patients the positive nitrogen balance was stated on the ward, caused first of all by decrease of the nitrogen excretion in the urine. Authors conclude that the decrease of body weight is caused on the hand by decrease of oral intake and resorption of nutrients in the shortened small intestine and on the other hand by inadequate physical load after operation.