The antioxidative and/or pro-oxidative potential of three trace metal ions, namely aluminum (Al), manganese (Mn), and selenium (Se), has been studied. The effect of Al and Mn was found to be anion independent. The pro-oxidative potential of Al was more prominent than its antioxidative potential. This may be due to its redox inert nature. The increase in lipid peroxidation rates in placental syncytiotroblast membranes may contribute to the etiology of aluminum toxicity. Selenium had an antioxidative potential only in the whole-cell homogenate. This appears to be mediated by glutathione peroxidase of which Se is a cofactor. Manganese proved to be the trace metal ion of choice. It decreased the production of thiobarbituric acid reactive substances (TBARS). This may be due to its capacity to quench the superoxide anion and hydroxyl radicals and also due to its chain-breaking capacity. During the present course, ferrous-ascorbate mediated lipid peroxidation has been studied using various combinations of FeSO4 and ascorbic acid. Extrapolating the combined ratio of the individual combination as substrate concentration ([S]) and treating the observed amount of malondialdehyde (MDA) produced equivalent to initial velocity (vi), as in the case of enzymatic studies, the data were treated according to Michaelis-Menten kinetics and the values of kc and Cmax have been calculated.
The effects of Gossypol acetic acid (10 mg/kg b. wt. daily for 15 days), an experimental male antifertility agent and its subsequent withdrawal for another 15 days, on the structure and functions of the rat small intestinal tract have been investigated. Gossypol feeding causes a reduction in body weight and intestinal weight, length, protein, and nucleic acid contents. A 27%-50% reduction in the uptake of glucose, alanine, leucine, and calcium is observed after Gossypol feeding which is found to be reversible after 15 days of withdrawal of the drug. Gossypol also causes a significant reduction in the activities of sucrase, lactase, maltase and alkaline phosphatase in the intestinal homogenates as well as in the purified brush border membrane of the microvillus. A decrease in the maximum of apparent enzyme velocity and no change in the substrate affinity constant in these digestive hydrolases are observed on Gossypol treatment. It also causes a shift in the transition temperature in these enzymes and predictably changes the energy of activation both below and above the temperature of transition, although the Arrhenius expression of the temperature dependence still shows proximity, non-linearity, and is parallel to the control group. These changes are reversed on withdrawal of the drug and during the subsequent recovery period. Recovery experiments also show near identical values in kinetic parameters (Kt and Jmax) of 14C-glucose uptake in jejunal segments both in the presence and absence of Na+ ions. Also, no difference is observed between the control and recovery groups with respect to body and intestinal weight, intestinal length, and DNA, RNA, protein, lactate dehydrogenase and glucose-6-phosphate phosphohydrolase values in the intestinal homogenates. Phospholipid, cholesterol and sialic acid levels in both the groups also show nearly identical values. Molecular mechanism of the effects of Gossypol on brush border membrane-bound enzyme/carrier molecules operation is discussed in view of the kinetic and thermodynamic data obtained.
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