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Biomedical subjects

J M Patel

Publications and source records attributed to J M Patel.

81 records · Page 5Linked to original sources
PubMedDate not supplied

Vitamin E distribution and modulation of the physical state and function of pulmonary endothelial cell membranes.

Vitamin E, a dietary antioxidant, is thought to incorporate into the lipid bilayer of biological membranes. We evaluated the lipid composition and distribution of [3H]-vitamin E in various membranes of pulmonary endothelial cells and determined whether vitamin E incorporation caused alterations in membrane structure and function in these cells. Following 6-, 12-, 18-, 24-, and 48-h incubation periods, vitamin E incorporation values were 3.0, 5.7, 6.9, 7.2, and 6.8 nmol/mg protein or 3.8, 7.3, 8.8, 9.2, and 8.7 nmol/mg phospholipid in mitochondrial membranes and 2.0, 4.4, 5.2, 5.3, and 5.0 nmol/mg protein or 3.5, 7.7, 9.1, 9.3, and 8.8 nmol/mg phospholipid in microsomal membranes, respectively. Vitamin E incorporation into the plasma membranes was greater than in mitochondrial and microsomal membranes after 12-, 24-, and 48-h incubations (18.9, 20.8, and 19.6 nmol/mg protein, respectively [P less than .001] versus mitochondria and microsomes or 12.2, 13.4, and 12.6 nmol/mg phospholipid, respectively [P less than .05] versus mitochondria and microsomes). The total phospholipid content, as well as the unsaturation index of the fatty acid content of these membranes, were in the same order, (i.e., plasma membrane greater than mitochondrial membranes and microsomal membranes). The physical state of the intact plasma membrane and the mitochondrial and microsomal membranes were measured by monitoring fluorescence anisotropies (rs) of the molecular probes, diphenylhexatriene (DPH) and trimethylamino-DPH (TMA-DPH). Vitamin E incorporation caused significant increases in rs for DPH (P less than .01) and TMA-DPH (P less than .01) in all three membranes compared to controls. Similar increases in rs values for DPH and TMA-DPH were observed in lipid vesicles prepared from these membranes. Following vitamin E incorporation, 5-hydroxytryptamine (5-HT) transport was measured as an index of plasma membrane function. Vitamin E incorporation resulted in an 18% reduction (P less than .05) in 5-HT uptake. These results indicate that vitamin E was distributed nonuniformly in endothelial cell membranes but resulted in comparable decreases in fluidity in all three membranes. In addition to its role as an antioxidant, vitamin E may alter the membrane physical state and modulate a variety of endothelial cell functions, including 5-HT transport.

Animals↗
PubMedDate not supplied

The biotransformation of p-xylene to a toxic aldehyde.

Rats given a single ip injection of p-xylene suffered 65% loss of pulmonary microsomal p-xylene hydroxylase activity. The activity was protected by pretreating the rats with phenobarbital, which increased hepatic p-xylene hydroxylase and cytosolic aldehyde dehydrogenase activities, but had no effect on alcohol dehydrogenase activity in hepatic cytosol. Pretreatment of rats with pyrazole caused a 60% inhibition of liver alcohol dehydrogenase but had no effect on liver aldehyde dehydrogenase activity. This treatment partially protected the pulmonary microsomal p-xylene hydroxylase from inactivation by p-xylene. Experiments in vitro showed that inactivation of cytochrome P-450 by p-xylene required the metabolic conversion of p-xylene to p-tolualdehyde. The reactive intermediate (p-tolualdehyde) required the presence of NADPH to carry out the inactivation. Inasmuch as lung tissues cannot form p-tolualdehyde (because of the low activity of p-methylbenzyl alcohol dehydrogenase), it is assumed that the inactivation of lung enzymes in vivo following exposure to p-xylene was due to the aldehyde intermediate which is formed in the liver and transported to the lung.

Aldehydes↗
PubMedDate not supplied

The biotransformation of allyl alcohol and acrolein in rat liver and lung preparations.

The biotransformation of allyl alcohol and acrolein by rat lung and liver preparations was investigated by measuring acrolein, acrylic acid, glycidol, and glycidaldehyde. Acrolein was detected by high-pressure liquid chromatography from incubation mixtures containing allyl alcohol, NAD+, and liver 9000g supernatant fraction or cytosol. Acrolein was not formed when lung fractions were treated similarly. Addition of pyrazole in the incubation mixture inhibited the reaction. The metabolism of acrolein to acrylic acid by liver 9000g supernatant fraction, cytosol, and microsomes has been demonstrated; acrylic acid formation was greater with NAD+ than with NADP+ in all three fractions. Acrylic acid was also formed from allyl alcohol. Disulfiram inhibited the NAD+- and NADP+-dependent reactions. Acrylic acid was not formed when lung preparations were used. Lung and liver microsomal epoxidation products of allyl alcohol and acrolein have been identified. Conversion of glycidol to glycerol and glycidaldehyde to glyceraldehyde by liver epoxide hydrase has been demonstrated. Epoxides, glycidol, and glycidaldehyde were also found to be substrates for lung and liver cytosolic glutathione S-transferase.

1-Propanol↗
PubMedDate not supplied

Selective inactivation of rat lung and liver microsomal NADPH-cytochrome c reductase by acrolein.

Addition of acrolein to rat lung or liver microsomal suspensions resulted in total inactivation of NADPH-cytochrome c reductase and partial conversion of cytochrome P-450 to P-420 in a concentration- and time-dependent fashion. Acrolein also caused total loss of nonprotein sulfhydryl content in both preparations, whereas protein sulfhydryl content was decreased by 40% and 28% in lung and liver preparations, respectively. Maxima of about 60% of the total lung cytochrome P-450 and 50% of the liver cytochrome P-450 in acrolein-treated microsomes did not support the N-demethylation of benzphetamine or ethylmorphine or hydroxylation of aniline because of the total loss of NADPH-cytochrome c reductase. Addition of purified NADPH-cytochrome c reductase to the acrolein-treated lung or liver microsomal suspension largely restored these monooxygenase activities. Addition of glutathione or dithiothreitol to the lung or liver microsomal suspension prior to the addition of acrolein significantly protected cytochrome P-450 from conversion to cytochrome P-420 as well as NADPH-cytochrome c reductase from inactivation. Thus, selective conjugation of acrolein with lung and liver NADPH-cytochrome c reductase but not cytochrome P-450 was responsible for total loss of these lung and liver monooxygenase activities.

Acrolein↗