In order to establish if dietary pectin could influence the levels of hepatic reduced glutathione (GSH) and the rate of lipid peroxide formation, we fed 8 male Balb C mice for 14 days with a standard powder diet supplemented with 5% highly methoxylated apple pectin. Another 8 mice received the standard powder diet only and served as controls. The animals were killed on the 15th day. The levels of GSH and lipid peroxides expressed in terms of malondialdehyde (MDA) were determined in liver homogenates. Besides, parameters that could be related to GSH metabolism or lipid peroxidation, such as the activity of γ-glutamyl transferase (γ-GT) and the content of iron, were assessed as well. In pectin-fed animals γ-GT activity was decreased (p<0.01), whereas the level of hepatic GSH was elevated (p<0.001). A negative correlation was established between both parameters. GSH correlated also negatively with lipid peroxides, which were reduced. Iron content was only slightly decreased. The data obtained suggest that the pectin-enriched diet could influence the antioxidant processes in the liver, increasing GSH levels (at least partially by lowering γ-GT activity) and reducing the formation of lipid peroxides.
The effect of intravenous hyperosmolar mannitol on delivery of liposomes to the brain was investigated. Pure CAMP phosphodiesterase was iodinated and entrapped in either dehydration-rehydration vesicles or small unilamellar vesicles composed of egg phosphatidyl-choline, cholesterol, and sulfatides. A time-course study of liposomal delivery to the brain after hyperosmolar mannitol administration showed increased delivery to the brain of dehydration-rehydration vesicles and of small unilamellar vesicles compared with their respective normal saline controls. Clearance of both free or liposomally-entrapped enzyme from the brain was slower under hyperosmolar conditions. Studies with FITC-BSA or morphine-BSA entrapped in small unilamellar vesicles further confirmed the delivery of liposomal contents to the brain, liver, and cultured glioma cells under hyperosmolar conditions. These data show that 2M mannitol is able to reversibly disrupt the blood-brain barrier and thereby increase the delivery of both free and liposomally-entrapped substances to the brain.
The mechanism responsible for the atherogenic effects of passive smoking was studied. Four weeks and 12 weeks of exposure of rats to tobacco sidestream smoke resulted in an increase in lipid peroxide contents, expressed as thiobarbituric-acid reactive substances, in low-density lipoprotein (LDL) and in aortic tissue. The LDL isolated from plasma exhibited elevations of 136, 155, and 170% over the control values for TBA, cholesterol, esterified cholesterol, respectively, whereas the corresponding increases in the aorta were 118, 148, and 254%, respectively. Electrophoretic examinations of LDL revealed a typical denatured LDL. Among esterified cholesterol-metabolizing enzymes in the aorta, lysosomal acid cholesteryl ester hydrolase, microsomal neutral cholesteryl ester hydrolase, and acyl coenzyme A: cholesterol acyltransferase were significantly suppressed by the 4 weeks' exposure; and further suppression of the acid cholesteryl ester hydrolase activity along with increases in the neutral cholesteryl ester hydrolase and acyl coenzyme A: cholesterol acyltransferase activities was observed after 12 weeks' exposure. A possible mechanism of the observed lipid accumulation in the aorta was discussed in connection with the effect of lipid peroxides in oxidatively modified-LDL on esterified cholesterol-metabolizing enzymes.
The effect of folic acid on lipoprotein lipase and various lipid fractions was studied in streptozotocin-induced diabetic rats. An enhanced plasma and hepatic lipoprotein lipase activity has been observed in folate supplemented diabetic animals. The proatherogenic triglycerides and very-low-density lipoprotein cholesterol+low-density lipoprotein cholesterol levels were found to be elevated in the diabetic groups, and folic acid supplementation lowered these levels. A significant increase in the antiatherogenic high-density lipoprotein cholesterol levels was observed in the diabetic rats on folate supplementation. The ratio of total cholesterol to high-density lipoprotein cholesterol of 3.93±1.56 observed in the diabetic groups was lowered to 2.04±0.25 on folate supplementation. These observations suggest a role for folic acid as an antiatherogenic agent in experimentally induced diabetes.
A rapid method was described earlier for estimation of total urinary pteridines, a method found suitable for monitoring cancer patients under therapy (Trehan and Noronha  J. Clin. Biochem. Nutr., 14, 195-2O3). This method was employed in the present study for monitoring development of Yoshida ascites tumor and regeneration of liver in partially hepatectomized rats. During tumor development the total urinary pteridines to creatinine ratio was found to increase progressively by more than five fold. The progressive increase in urinary pteridine levels correlated well with the tumor development. However, when partially hepatectomized rats with rapidly regenerating normal liver cells were monitored over a 13-day post-hepatectomy period, almost normal excretory levels of pteridines were found throughout this regeneration period. This clearly brings out that though both the systems investigated involved proliferating cells, the increased urinary pteridine excretion was associated solely with malignant cell growth and not with proliferating normal tissue.
Tissue and cellular distribution of NK341 (recombinant Cu, Zn-SOD) after intravenous administration in rats was examined by autoradiography and an immunohistochemical technique. Upon observation of the autoradiograms, NK341 was found to be distributed diffusely in well-perfused tissues (liver, heart, kidney, and lung) at 5min, and subsequently to be concentrated in the kidney cortex. Elimination of NK341 from other tissues was observed at 30min after administration. These results indicate that NK341 became localized solely in the cortex of the kidney. Radioactivity in the kidney decreased with time, but was still detected even in a small amount at 144h after administration. In order to examine NK341 distribution in more detail, we performed immunoperoxidase and acid phosphatase staining studies. In the kidney, NK341 was observed in lysosomes of proximal tubule cells, but not detected in glomeruli and other sections. Since the immunoperoxidase method, which should solely detect the antigenic NK341 protein, failed to yield positive staining at 144h after administration, the remained radioactivity in the kidney at this interval might be attributed to be the existence of metabolites. In the liver and heart, NK341 was detected in Kupffer cells and macrophages, respectively, but not in the hepatocytes or myocytes.
An extract of autologous Lactobacillus casei cell lysate (LEx) is known to lower the blood pressure of spontaneously hypertensive rats (SHR). To determine the effects of LEx in humans, we enrolled twenty-eight patients with an average age of seventy-one years and with an average systolic blood pressure/diastolic blood pressure of 164/96mmHg in a 2-month, double-blind, placebo-controlled study. Four hundred milligrams of LEx or placebo powder enclosed in white capsules was given twice a day for 2 months. Decreases in systolic blood pressure (p<0.01), diastolic blood pressure (p<0.05), and heart rate (p<0.05) were observed in the LEx-treated group when compared with the baseline. As to the blood plasma component, both total cholesterol and fasting plasma glucose were reduced (p<0.05) in the LEx-treated group. These findings support the role of LEx in the treatment of hypertension with beneficial effects on glucose and lipid metabolism.