Alternative pathway of glucose metabolism in developing human foetal heart.
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Biomedical subjects
Publications and source records attributed to K De.
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Exploratory studies on drug induced lipid peroxidation in goat whole blood and its inhibition with antioxidants were carried out using sodium ceftriaxone (CTS) as the representative drug and glutathione and probucol as the representative antioxidants. The studies showed that CTS could induce lipid peroxidation to a significant extent. Lipid peroxidation is a toxicity mediating process, this finding may be correlated with the toxic potential of the drug. It was further found that glutathione and probucol caused significant suppression of CTS induced lipid peroxidation. The results suggest that glutathione and probucol merit further assessment to explore their potential to reduce drug induced lipid peroxidation and thus to increase therapeutic index of the drug by way of reducing toxicity that may be mediated through free radical mechanism.
Considering importance of the lipophilicity of norethindrone (log P=2.97), a significant contributor to its mechanism of action, interaction of the drug with total lipids of goat whole blood have been investigated using phospholipid binding, fatty acid composition and peroxidation phenomena as the parameters under investigation. The objective was to derive an insight into the pharmacodynamic behavior of the drug by correlating biological activity with drug induced changes in lipid constituents. Significant loss in phospholipid along with changes in fatty acid cotmposition was observed after incubation of whole blood with norethindrone at 56 ng/ml (effective contraceptive concentration in blood) in varying periods of time. This may be ascribed to binding affinity of norethindrone with lipid constituents in blood. Lipid binding potential of the drug may have a role in its therapeutic effect. Lipid peroxidation induction potential of norethindrone was quantitatively measured in the context of its toxicity. The results reveal that northindrone caused significant extent of lipid peroxidation. Ascorbic acid, a promising antioxidant, at equivalent human dose levels of 250 mg and 500 mg could significantly reduce norethindrone induced lipid peroxidation.
Protective effects of three free radical scavengers, tocopherol (TOC), probucol (PR) and ascorbic acid (AA), on cardiotonic glycoside digoxin (DIG) induced lipid peroxidation in goat liver homogenate, have been studied by measuring malondialdehyde and glutathione contents as indicator parameters. The level of reduced glutathione decreased vis-a-vis malondialdehyde content increased in the drug treated samples in comparison with the controls. This suggests that DIG may have significant lipid peroxidation induction capacity. Considering lipid peroxidation as a toxicity mediating process, this may be related to the toxic potential of the drug. When the liver homogenate samples were incubated with antioxidant (TOC/PR/AA) in conjunction with the drug (DIG), lipid peroxidation was suppressed as indicated by increased level of reduced glutathione and decreased level of malondialdehyde in comparison with those of drug treated samples. This indicates that TOC, PR and AA may have considerable suppressive action on DIG induced lipid peroxidation. Thus, these antioxidants merit further extensive study to explore their potential in reducing DIG induced toxicity that may be mediated by free radical mediated process.
The activities of different testicular enzymes, as a marker of development, have been determined at various gestational ages. The enzyme sorbitol dehydrogenase shows peak activity between 25 and 28 weeks of gestation, whereas the peak of hyaluronidase was observed between 14 and 16 weeks of gestation. The activities of pentose phosphate enzymes, such as glucose-6-phosphate dehydrogenase and transketolase in developing human fetus reach the highest level between 25 and 28 weeks and 21 and 24 weeks of gestation, respectively, indicating the most actively synthesizing period of the fetus for providing NADPH and ribose-5-phosphate for steroidogenesis and nucleotide and nucleic acid synthesis.