Flavonoids are potent inhibitors of the oxidative modification of low-density lipoprotein (LDL), and foods containing these compounds have been shown to be negatively associated with coronary heart disease (CHD). Flavonoids reduce the formation of free radicals and protect or regenerate other antioxidants; or alternatively, they chelate divalent metal ions. Isoflavones may act in a manner similar to estrogen in that they lower LDL and in this way confer protection against CHD. Less is known about other minor dietary constituents, such as boron, which is widespread in fruits and vegetables. Boron may have an impact on CHD by inducing small increases in the concentration of plasma estrogen.
In order to develop a simple and reliable assay method for lipid hydroperoxides in serum or plasma, we sought to determine the suitable conditions for direct application of the previously reported colorimetric method using a methylene blue derivative, 10-(N-methylcarbamoyl)-3, 7-(dimethylamino)-phenothiazine, for the measurement of lipid hydroperoxides in a sample without extraction of them with organic solvents. For such purpose, dissociation of lipid hydroperoxides from proteins by lipoprotein lipase was found to be necessary. Also, we found that holotransferrin, which oxidizes the methylene blue derivative, should be eliminated by its chelation with trimethylenetetraminehexaacetic acid. Pretreatment of the sample with ascorbate oxidase was also necessary to eliminate interference by ascorbic acid in a sample. Thus the recommended method is to mix the sample with lipoprotein lipase, trimethylenetetraminehexaacetic acid, ascorbate oxidase, and the detergent Triton X-100, then to incubate the mixture with the methylene blue derivative dissolved in the detergent in the presence of hemoglobin, and to measure the oxidized product, methylene blue. The amount of lipid hydroperoxides is calculated by use of an external standard, either linoleic acid hydroperoxide or cumene hydroperoxide.
As the nutritional status of an individual is important in the regulation of xenobiotic metabolism brought about by the activation and detoxification enzymes of mixed function oxidase systems, the balance of these reactions ultimately determines the fate of xenobiotic agents and thereby modulates their toxic, mutagenic, and carcinogenic effects. Among the dietary factors vitamin C has attracted special attention because of its non-toxic nature and tumor prophylactic effects on a number of experimentally induced tumors. In this study we evaluated the effect of N-nitrosodiethylamine (NDEA), a potent environmental carcinogen, on the status of the Ah-receptor (involved in the induction of arylhydrocarbon hydroxylase) in guinea pigs fed excessive doses of ascorbic acid. The Ah-receptor was estimated by two methods, hydroxylapatite assay and Sephacryl S-300 column chromatography. We found that in both the assays the level of Ah-receptors was significantly decreased in excessive ascorbic acid-fed guinea pigs treated with NDEA. The hydroxylapatite method, which was more convenient, fast and economical is to be preferred for the assay of the Ah-receptor.
Cisplatin, an antitumor chemotherapeutic agent with doselimiting nephrotoxic side effects, was administered i.p, to male albino rats at a concentration of 6mg/kg body wt. The antioxidant vitamin E (400mg/kg body wt., orally) and the diuretic acetazolamide (ACZ) (20mg/kg body wt., i.p.) were co-administered as modulators. The effect of cisplatin on lipid peroxidation and antioxidant enzyme levels was then examined. The agent increased the level of lipid peroxidation and significantly decreased the activities of antioxidant enzymes. These effects may have been due to the formation of free radicals and were considered to be one of the reasons for cisplatin-induced nephrotoxicity. Interestingly, these changes were found to be very much counteracted by vitamin E and acetazolamide when they were co-administered along with the cisplatin. Hence, we suggest that co-administration of vitamin E and acetazolamide along with cisplatin will be clinically advantageous in attenuating cisplatin-induced nephrotoxicity during chemotherapy.
Tincture of Crataegus (TCR) is an antiatherogenic drug consisting of flavonoids, some saponins, and cardioactive amines. It is an alcoholic extract of the berries of the tree Crataegus oxyacantha, commonly called the hawthorn. TCR at a dosage of 0.5ml/100g body weight/day for 6 weeks could prevent the increase in lipid peroxidation observed in rats with experimentally induced atherosclerosis. TCR also prevented the decrease in glutathione and α-tocopherol content of the liver, aorta, and heart. The decreased activities of some antioxidant enzymes in liver, aorta, and heart tissues were also maintained at normal levels by the drug. TCR also prevented the copper ion-induced oxidation of low-density and very-low-density lipoproteins in vitro. The antiatherogenic effect of TCR appears to be related to its antioxidant property. It is possible that the constituents of TCR act synergistically to ameliorate the oxidative stress during atherogenesis.
Decreased activities of Na+, K+-ATPase in liver and kidney, Mg2+-ATPase in kidney, and Ca2+-ATPase in liver were observed in alcoholic rats (3.0g of ethanol/kg body weight, 30% [v/v]) given twice daily for 30 days compared with those of the controls. Increased activities of Ca2+-ATPase in kidney and Mg2+-ATPase in liver were also observed in the alcoholic rats. All the above metabolic alterations induced by alcohol were effectively avoided by L-cysteine (20mg/100g body weight) given twice daily for 30 days.
Immunoblot analysis for urinary fibronectin (FN) of normal and passive Heymann nephritis (PHN) rats was performed. When 2-5% skim milk or 2-10% bovine serum albumin solution was used as a blocking buffer for the immunoblot analysis, remarkable nonspecific interactions were observed between many urinary proteins and immunoglobulins used as a primary as well as a secondary antibody. Blocking of the transblot membrane with a 2% γ-globulin solution prevented such nonspecific interactions. As a result, two FN fragments, not intact FN, with molecular masses of 55- and 65-kDa were detected in all the normal rat urine samples. In PHN rat urine, intact FN and several FN fragments of 100-200-kDa were evident instead of the 55- and 65-kDa FN fragments. These results indicate that metabolism of FN and excretion of the FN metabolites into urine may be changed during the development of the renal disease.