Lung Retinoid Metabolism and Signaling in Chronic Obstructive Pulmonary Disease.

There are a number of sites that are required for the production and/or action of all-trans retinoic acid (ATRA). In particular, interruption of different components of the chain of trafficking and metabolism has been associated with cancers arising in numerous organs of the body. Preliminary work suggests that such interruptions may be a factor in lung disorders induced by the smoke exposure. The active metabolite of retinoid, ATRA offers a therapeutic strategy to protect against functional abnormality in the lung, including chronic obstructive pulmonary disease (COPD). This review deals with the lung retinoid metabolism and mediators of retinoid trafficking and signaling with special emphasis on their roles in health and disease.

Environmental contaminants in pathogenesis of breast cancer.

This review is an attempt to comprehend the diverse groups of environmental chemical contaminants with a potential for pathogenesis of breast cancer, their probable sources and the possible mechanisms by which these environmental contaminants act and interplay with other risk factors. Estrogens are closely related to the pathogenesis of breast cancer. Oxidative catabolism of estrogen, mediated by various cytochrome P450 enzymes, generates reactive free radicals that can cause oxidative damage. The same enzymes of estrogenic metabolic pathways catalyze biological activation of several environmental (xenobiotic) chemicals. Xenobiotic chemicals may exert their pathological effects through generation of reactive free radicals. Breast tissue can be a target of several xenobiotic agents. DNA-reactive metabolites of different xenobiotic compounds have been detected in breast tissue. Many phase I and II xenobiotic metabolizing enzymes are expressed in both normal and cancerous breast tissues. These enzymes play a significant role in the activation/detoxification of xenobiotic and endogenous compounds including estrogens. More than 30 carcinogenic chemicals are present in tobacco smoke; many of them are fat-soluble, resistant to metabolism and can be stored in breast adipose tissue. Similarly, pesticides are also known to cause oxidative stress; while some act as endocrine disruptor, some are shown to suppress apoptosis in estrogen sensitive cell lines. Reports have shown an association of smoking (both active and passive) and pesticides with breast cancer risk. However, the issues have remained controversial. Different mutagenic substances that are generated in the cooking process e.g., heterocyclic amines and polycyclic aromatic hydrocarbons (PAHs) can be a threat to breast tissue. PAHs and dioxins exert their adverse effects through the aryl hydrocarbon receptor (AhR), which activates several genes involved in the metabolisms of xenobiotic compounds and endogenous estrogens. These chemicals also induce AhR-dependent mitochondrial dysfunction. Many of the environmental pollutants suppress the immune system, which are implicated to risk. A better understanding about the biological effects of different environmental carcinogenic compounds and determination of their impact on rising incidence of breast cancer will be beneficial in improving preventive policy against breast cancer.

Alteration of lipid composition, Na+, Κ+-ATPase and Δ5-3ß-hydroxy steroid dehydrogenase activities in microsomal membranes of mature toad ovary in different seasons.

Microsomal membranes isolated by sucrose density gradient centrifugation from mature toad ovary has been found to vary significantly in lipid composition and various enzyme activities in different seasons. Na+, Κ+-ATPase activity is the highest in breeding season (rainy season). Significantly the optimum temperature for enzyme activity is 30°C. The other enzyme Δ5-3ß-hydroxysteroid dehydrogenase activity is also lower in hibernation period than other seasons. The total phospholipid, sterol and fatty acid contents differ significantly between seasons. The poly-unsaturated fatty acid, except arachidonic acid content in hibernation period is much lower than that during other seasons. The sterol content is also the lowest in this season. The present findings indicate that during hibernation period the membrane is more rigid and the metabolic activity of the animal is slow because of a lower level of various functionally important enzyme activities.

Hydrogen peroxide formation and lipid peroxidation in rat uterus— effect of hormones and vitamin Ε.

The effect of estradiol–17ß and progesterone given separately as well as in combination on the rate of hydrogen peroxide formation and lipid peroxidation in the uteri of ovariectomized rats was studied. Estradiol in 3 μg dose per day per animal elicited maximum stimulatory response and progesterone (100 μg), on the other hand, was without any such effect. However, progesterone given along with estradiol completely prevented the effect due to the latter. In the same way, vitamin E, a well known antioxidant was found to be extremelv effective in protecting the uterus from the highly peroxidative action of estradiol–17ß.

Prostaglandin-synthetase activity in developing toad ovary— I. Detection and properties.

Prostaglandin-synthetase activity has been measured in the microsomal fraction of developing toad (Bufo melanostictus) ovary using arachidonic acid as the substrate. Indomethacin (0·74 μΜ) and aspirin (0·35 μΜ) inhibit this activity. The activity is maximum in immature ovary and its level gradually decreases with maturity of the organ till the breeding season arrives, when it rises again. Time course study shows that the activity in vitro becomes steady after 3 min of incubation in all the cases, except the immature ones in which it sharply declines. Soluble supernatant was found to contain some inhibitory factor(s), which is partially inactivated by heating at 100°C for 5 min (~ 43%). Intraperitoneal injection of equine luteinizing hormone stimulates this enzyme activity in the mature ovary during non-breeding season. This suggests that similar to mammalians prostaglandin-synthetase, the toad ovary enzyme is also regulated by luteinizing hormone.