Tapan Dey

Role of glutathione S transferase polymorphism in COPD with special reference to peoples living in the vicinity of the open cast coal mine of Assam.

Background COPD may develop due to variation in the functioning of antioxidants along with smoking and environmental factors in genetically susceptible individuals. Since there are different views about the antioxidants responsible for detoxifying xenobiotic compound in the human body whose functional variation may lead to obstructive disease, this associative study has been taken up between GST gene polymorphism and COPD in populations exposed to coal dusts. Methods Genotypes of the 70 COPD patients and 85 non COPD patients were determined by PCR based methods followed by multiplex PCR of GSTT1 and GSTM1 genes taking albumin gene as a control. Suspended particulate analyses were determined through the Respirable Dust sampler along with the FTIR analysis of the dust samples from the glass microfiber filters. Results Dust sampling analysis reveals higher level of respirable suspended particulate matter, non respirable particulate matter, SO2 and NO2 present in air of the study site. FTIR analysis also suggests a higher concentration of organic silicone and aliphatic C-F compounds present in air of the study site and when spirometry was done, low lung function was observed among most of the subjects. GSTM1 null type was significantly associated with low lung function in smoker groups and the presence of at least one active allele (either GSTM1/GSTT1) seemed to have a protective role in the development of COPD. Conclusions GSTM1 (null genotype) appeared to be a risk factor for lower lung function in smokers living in the vicinity of coal mines. Apart from polluted environment and genetic susceptibility, mixed coal dust exposure rich in organic silicone and aliphatic C-F compounds also appears to be a factor for the low lung function.

Antioxidant Potential of Vespa affinis L., a Traditional Edible Insect Species of North East India

Introduction Elevated oxidative stress plays an important role in the pathogenesis of health disorders, like arthritis. Traditionally, Vespa affinis L., a common edible insect among many tribes in North-East India, is believed to have a beneficial role in extenuating health disorders, such as arthritis. The present study investigated the molecular mechanism underlying medicinal benefit of the Aqueous Extract of Vespa affinis L. (AEVA) against oxidative stress pathophysiology. Methods The free radical scavenging activities of AEVA were examined against DPPH, hydroxyl, and superoxide radicals and the effect on the activities of antioxidant enzyme (GST and CAT) was determined using both recombinant proteins and human plasma. The antioxidant potential of AEVA was again investigated using THP-1 monocytes. Results AEVA possesses a significant free radical scavenging activity as evident from the DPPH, superoxide, and hydroxyl radical scavenging assay. Incubation of AEVA (2.5, 5, 7.5, and 10 μg/μL) with the recombinant antioxidant enzymes, rGST and rCAT significantly increased the enzyme activities compared to those observed in corresponding enzyme alone or AEVA itself. AEVA supplementation (5, 7.5, and 10 μg/μL) also stimulates the activities of GST and CAT when incubated with human plasma. A cell culture study also confirmed the beneficial role of AEVA (0.8 and 1.2 μg/μL) which enhances the activities of GST and CAT, and also reduces the intercellular ROS production in monocytes treated with or without H2O2 and the effects are at par with what is observed in N-acetyl cysteine-treated cells. Conclusion The antioxidant potential of the aqueous extract of Vespa affinis L. may mediate its therapeutic activities in oxidative stress-associated health disorders.

Circulatory heavy metals (cadmium, lead, mercury, and chromium) inversely correlate with plasma GST activity and GSH level in COPD patients and impair NOX4/Nrf2/GCLC/GST signaling pathway in cultured monocytes

This study aims to examine the hypothesis that circulatory heavy metals may be associated with lung function decline and lower plasma GST activity and GSH level in COPD patients via activating monocytes mediated by impairing the NOX4/Nrf2/GCLC/GST signaling pathway. Results showed that the blood levels of heavy metals (cadmium, lead, mercury, and chromium) were significantly higher in COPD patients of coal mine site compared to the healthy controls. The levels of heavy metals in COPD patients were significantly and negatively correlated with lung function, GST activity, and GSH level. Using flowcytometry, fluorescence spectroscopy, and immunoblotting studies we have further demonstrated that treatment with individual heavy metals dose-dependently increased the NOX4 protein expression, intracellular ROS production, and decreased the Nrf2, GCLC, and GST protein expression, GST activity, and GSH level in THP-1 monocytes. None of the treatment caused any change in cell viability compared to control. In conclusion, this study suggests that circulatory heavy metals in COPD patients of coal mine site weakened the lung function, decreased the plasma GST activity and GSH level via impairing the NOX4/Nrf2/GCLC/GST signaling pathway in monocytes, which may cause monocyte activation and initiate the COPD pathophysiology.

Therapeutic potentials of Houttuynia cordata Thunb. against inflammation and oxidative stress: A Review

Abstract Ethnopharmacological relevance Houttuynia cordata Thunb. (Family: Saururaceae) is an herbaceous perennial plant that grows in moist and shady places. The plant is well known among the people of diverse cultures across Japan, Korea, China and North-East India for its medicinal properties. Traditionally the plant is used for its various beneficial properties against inflammation, pneumonia, severe acute respiratory syndrome, muscular sprain, stomach ulcer etc. Oxidative stress and inflammation were found to be linked with most of the diseases in recent times. Many ancient texts from Chinese Traditional Medicine, Ayurveda and Siddha, and Japanese Traditional medicine have documented the efficacy of H. cordata against oxidative stress and inflammation. Aim of the study This review aims to provide up-to-date and comprehensive information on the efficacy of H. cordata extracts as well as its bioactive compounds both in vitro and in vivo, against oxidative stress and inflammation Materials and methods Relevant information on H. cordata against oxidative stress and inflammation were collected from the established scientific databases such as NCBI, Web of Science, ScienceDirect, Elsevier, and Springer. Additionally, a few books and magazines were also consulted to get the important information. Results Herbal medicines or plant products were traditionally being used for treating the oxidative stress and inflammation related diseases in diverse communities across the world. Scientifically, H. cordata has shown to target several signaling pathways and found to effectively reduce the oxidative stress and inflammation. Phyto-constituents such as afzelin, hyperoside and quercitrin have shown to reduce inflammation both in vitro and in vivo models. These molecules were also shown to have strong antioxidant properties both in vivo and in vitro models. Conclusions H. cordata extracts and its bioactive molecules were shown to have both anti-inflammatory and anti-oxidative properties. As both in vitro and in vivo studies were shown that H. cordata did not have any toxicity on the various model systems used, future clinical studies will hopefully make an impact on the future direction of treating inflammation-related diseases.

Proteases and Their Inhibitors in Chronic Obstructive Pulmonary Disease

In the context of respiratory disease, chronic obstructive pulmonary disease (COPD) is the leading cause of mortality worldwide. Despite much development in the area of drug development, currently there are no effective medicines available for the treatment of this disease. An imbalance in the protease: Antiprotease ratio in the COPD lung remains an important aspect of COPD pathophysiology and several studies have shown the efficacy of antiprotease therapy in both in vitro and in vivo COPD models. However more in-depth studies will be required to validate the efficacy of lead drug molecules targeting these proteases. This review discusses the current status of protease-directed drugs used for treating COPD and explores the future prospects of utilizing the potential of antiprotease-based therapeutics as a treatment for this disease.

Anti-Proliferative Activities of Vasicinone on Lung Carcinoma Cells Mediated via Activation of Both Mitochondria-Dependent and Independent Pathways

Vasicinone, a quinazoline alkaloid from Adhatoda vasica Nees. is well known for its bronchodilator activity. However its antiproliferative activities is yet to be elucidated. Here-in we investigated the anti-proliferative effect of vasicinone and its underlying mechanism against A549 lung carcinoma cells. The A549 cells upon treatment with various doses of vasicinone (10, 30, 50, 70 µM) for 72 h showed significant decrease in cell viability. Vasicinone treatment also showed DNA fragmentation, LDH leakage, and disruption of mitochondrial potential, and lower wound healing ability in A549 cells. The Annexin V/PI staining showed disrupted plasma membrane integrity and permeability of PI in treated cells. Moreover vasicinone treatment also lead to down regulation of Bcl-2, Fas death receptor and up regulation of PARP, BAD and cytochrome c, suggesting the anti-proliferative nature of vasicinone which mediated apoptosis through both Fas death receptors as well as Bcl-2 regulated signaling. Furthermore, our preliminary studies with vasicinone treatment also showed to lower the ROS levels in A549 cells and have potential free radical scavenging (DPPH, Hydroxyl) activity and ferric reducing power in cell free systems. Thus combining all, vasicinone may be used to develop a new therapeutic agent against oxidative stress induced lung cancer.

Antioxidant and glucose metabolizing potential of edible insect, Brachytrupes orientalis via modulating Nrf2/AMPK/GLUT4 signaling pathway

Brachytrupes orientalis (Gryllidae) is a common edible insect species eaten by the different tribes of North East India. This study investigated the potentiality of Brachytrupes orientalis extracts in different solvent hydro-alcoholic (AEBO), hexane (HEBO) and ethyl acetate (EEBO) on glucose utilization and cell viability in high glucose (HG) treated myotubes. It has been observed that AEBO supplementation significantly increased the glucose utilization against HG exposure; however, treatment HEBO and EEBO have no significant effect. AEBO also increased the intercellular glucose-6-phosphate level and the protein expression of both phospho-AMPK and GLUT4 in HG treated myotubes in a dose dependent manner. Furthermore, supplementation with AEBO decreased the intercellular ROS production, lipid peroxidation, and up-regulated the protein expression of Nrf2 and GST. Chromatography and Spectroscopic analyses of AEBO also suggest that Ursolic acid may be one of the bioactive principles with rich potassium, sodium, calcium and magnesium content.

Role of Environmental Pollutants in Liver Physiology: Special References to Peoples Living in the Oil Drilling Sites of Assam

The populations residing near polluted sites are more prone to various types of diseases. The important causes of air pollution are the suspended particulate matter, respirable suspended particulate matter, sulfur dioxide and nitrogen dioxide. As limited information is available enumerating the effect of these pollutants on liver physiology of the population living near the polluted sites; in the present study, we tried to investigate their effect on liver of the population residing near the oil drilling sites since birth. In this study, a randomly selected 105 subjects (46 subjects from oil drilling site and 61 subjects from control site) aged above 30 years were taken under consideration. The particulate matter as well as the gaseous pollutants, sulfur dioxide and nitrogen dioxide, were analyzed through a respirable dust sampler. The level of alkaline phosphatase, alanine transaminase and aspartate transaminase enzymes in serum were measured by spectrophotometer. The generalized regression model studies suggests a higher concentration of respirable suspended particulate matter, suspended particulate matter and nitrogen dioxide lowers the alkaline phosphatase level (p<0.0001) by 3.5 times (95% CI 3.1-3.9), 1.5 times (95% CI 1.4 - 1.6) and 12 times (95% CI 10.74 -13.804), respectively in the exposed group. The higher concentration of respirable suspended particulate matter and nitrogen dioxide in air was associated with increase in alanine transaminase level (p<0.0001) by 0.8 times (95% CI 0.589-1.049) and by 2.8 times (95% CI 2.067-3.681) respectively in the exposed group. The increase in nitrogen dioxide level was also associated with increase in aspartate transaminase level (p<0.0001) by 2.5 times (95% CI 1.862 – 3.313) in the exposed group as compared to control group. Thus, the study reveals that long-term exposure to the environmental pollutants may lead to liver abnormality or injury of populations living in polluted sites.