Debashis Bandyopadhyay

Oxidative stress-induced ischemic heart disease: protection by antioxidants.

Heart disease is one of the major health problems of advanced as well as developing countries of the world. Extensive research through the last decade has shown beyond doubt that free radicals, particularly, reactive oxygen species play a cardinal role in the pathogenesis of oxidative myocardial damage with consequential cardiac malfunction. This review presents a comprehensive account of the present day knowledge regarding the oxygen free radicals involved in the genesis of ischemic heart disease, the mechanism(s) of oxidative myocardial damage and the endogenous as well as exogenous antioxidant defense systems. Furthermore, the role of ischemic pre-conditioning, some antioxidants and the ability of some cardioprotective drugs in providing protection against the ischemic myocardial damage are also discussed. The text of the article comes to an end with a commentary on the future research perspective in the concerned area, which throws a light on the development of combinatorial therapeutics in the treatment of ischemic myocardial disease.

Gastric toxicity and mucosal ulceration induced by oxygen-derived reactive species: protection by melatonin.

Uncontrolled hydrochloric acid secretion and ulceration of the stomach mucosa due to various factors are serious global problems. Although the mechanism of acid secretion from the parietal cell is now well understood, the processes involved in gastric ulceration are still not clear. Among various causes of gastric ulceration, lesions caused by stress, alcohol consumption, Helicobacter pylori infection and due to use of nonsteroidal antiinflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species, especially the hydroxyl radical. A number of excellent drugs have proven useful in controlling hyperacidity and ulceration but their long-term use is associated with disturbing side-effects. Hence, the search is still on to find a compound possessing antisecretory, antiulcer and antioxidant properties which will serve as a therapeutic agent to reduce gastric hyperacidity and ulcers. This article describes the role of reactive oxygen species in gastric ulceration, drugs controlling them with their merits and demerits and, the role of melatonin, a pineal secretory product, in protecting against gastric lesions. In experimental studies, melatonin has been shown to be effective in reducing mucosal breakdown and ulcer formation in a wide variety of situations. Additionally, the low toxicity of melatonin supports further investigation of this molecule as a gastroprotective agent. Finally, we include a commentary on how melatonin research with respect to gastric pathophysiology can move forward with a view of eventually using this indole as a therapeutic agent to control gastric ulceration in humans.

Melatonin protects against oxidative damage and restores expression of GLUT4 gene in the hyperthyroid rat heart

Abstract:u2002 To understand the mechanism of cardiovascular dysfunction in the hyperthyroid condition, the role of oxidative stress was examined in rats treated with 3,5,3′‐triiodo‐l‐thyronine (T3). Treatment of rats daily with T3 (8u2003μg/100u2003g BW) for 15u2003days resulted in an increase in heart weight to body weight ratio, which was ameliorated by antioxidants, melatonin (2u2003mg/100u2003g BW) or vitamin E (4u2003mg/100u2003g BW). Both melatonin and vitamin E also inhibited rises of lipid peroxidation and hydroxyl radical generation and prevented the inhibition of Cu,Zn‐superoxide dismutase in the hypertrophic heart. The expression of the glucose transporter, GLUT4, was reduced in response to T3, which was completely restored by melatonin and partially by vitamin E. However, neither antioxidant prevented down regulation of peroxisome proliferator‐activated receptor‐α in the hyperthyroid heart. Furthermore, the reduced level of myocyte enhancer factor‐2, a regulator of GLUT4 transcription was restored completely by melatonin and partially by vitamin E treatment. Glucose uptake in hypertrophic left ventricular cells was also restored by these antioxidants. The expression of B‐type natriuretic peptide, a marker of heart failure, was significantly increased by T3 and ameliorated by melatonin or vitamin E treatments. In general, the beneficial effects of melatonin given as a co‐treatment with T3 were better than those induced by vitamin E. These data show that melatonin ameliorates hypertrophic growth of the myocardium induced by hyperthyroidism and provide an insight into the mechanism of reactive oxygen species‐mediated down regulation of metabolically important genes such as GLUT4 in the heart.

Melatonin protects against piroxicam-induced gastric ulceration

Abstract:u2002 The antiulcer effect of melatonin on gastric lesions caused by piroxicam was studied with the intent of determining the mechanism of action of this agent. Melatonin dose‐dependently lowered piroxicam and indomethacin‐induced gastric damage with more than 90% inhibition at a dose of 60u2003mg/kg BW. Increased lipid peroxidation, augmented protein oxidation and decreased glutathione content of the gastric tissue following piroxicam treatment indicated a possible involvement of oxidative stress in this nonsteroidal anti‐inflammatory drug (NSAID)‐induced gastropathy. Pretreatment of rats with melatonin prevented these changes. Oral administration of piroxicam to rats caused a threefold increase in the tissue levels of hydroxyl radical generation, a change significantly attenuated by melatonin. Furthermore, a decrease in the activity of gastric peroxidase and an increase in the activity of gastric superoxide dismutase(s) (SOD) because of piroxicam treatment was attenuated by melatonin pretreatment indicating that the indole possibly exerts its gastroprotective effects through its direct as well as indirect antioxidant activities. The results of the present studies also reveal that melatonin may influence the expression of Cu‐Zn SOD, catalase, cyclooxygenase as well as alpha‐actinin whose levels were found to be altered, following piroxicam treatment. The current studies, therefore, document melatonins gastroprotective ability against piroxicam‐induced gastric damage and the findings raise the possibility of melatonin being considered as a co‐therapy with piroxicam or other NSAIDs in reducing the gastropathy when long‐term use of these nonsteroidal agents are unavoidable.

Reactive Oxygen Species-Induced Gastric Ulceration: Protection By Melatonin

Gastric hyperacidity and ulceration of the stomach mucosa due to various factors are serious health problems of global concern. Although the mechanism of acid secretion from the parietal cells is now well understood, the processes involved in gastric ulceration are still not clear. Among the various causes of gastric ulceration, lesions caused by stress, alcohol consumption, Helicobacter pylori and due to use of non-steroidal anti-inflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species, especially the hydroxyl radical. A number of excellent drugs, developed over the decades, have proven useful in controlling hyperacidity and ulceration although their long-term use is reported to be associated with various side effects. Hence the investigations continue with an objective to find a compound possessing anti-secretory, anti-ulcer and antioxidant properties which will serve as a therapeutic agent to reduce gastric hyperacidity and ulcers. This article describes the role of reactive oxygen species in gastric ulceration, briefly presents a note on the currently available drugs controlling them, and focuses on the role of melatonin, a pineal secretory product, in protecting against gastric lesions. In experimental studies, melatonin has been shown to be effective in reducing mucosal breakdown and ulcer formation in a wide variety of situations. Additionally, the low toxicity of melatonin supports further investigation of this molecule as a promising gastro-protective agent. Finally, we include a commentary on how melatonin research with respect to gastric pathophysiology can move forward with a view to eventually using this indole as a therapeutic agent alone or in combination with the existing drugs to control gastric ulceration in humans in order to increase their efficacy and/or to reduce their side effects.

A Practical Green Synthesis and Biological Evaluation of Benzimidazoles Against Two Neglected Tropical Diseases: Chagas and Leishmaniasis

Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Two very common neglected tropical diseases are Chagas disease and leishmaniasis. Chagas disease is a severe health problem, mainly in Latin America, causing approximately 50000 deaths a year and millions of people are infected. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. On the other hand, Leishmaniasis represents complex diseases with an important clinical and epidemiological diversity. It is endemic in 88 countries 72 of which are developing countries and it has been estimated that are 12 million people infected and 350 million are in areas with infection risk. On this basis, research on organic compounds that can be used against these two diseases is an important target. A very simple, green, and efficient protocol is developed in which bismuth nitrate pentahydrate is employed as a Lewis acid catalyst in aqueous media under microwave irradiation for the synthesis of various 2-aryl substituted benzimidazoles from aldehydes and o-phenylenediamine. Other salient features of this protocol include milder conditions, atom-economy, easy extraction, and no wastes. Nine 1H-benzimidazole derivatives (1-9) with substituents at positions 2 and 5 were synthesized and the structure of the compounds was elucidated by spectroscopic methods. The compounds were screened to identify whether they posses pharmacological activity against Chagas disease and leishmaniasis. Compound 8 showed better activity than the control Nifurtimox against INC-5 Trypanosoma cruzi strain whereas compounds 3 and 9 have demonstrated potent leshmanicidal activity. A systematic green synthetic procedure and in vitro biological evaluation of nine 1H-benzimidazoles are described.

Emergence of IPR Regimes and Governance Frameworks

This chapter provides an introductory discussion about the evolution of IPR regimes; the emergence of IPR protection of life forms; an overview of the various governance frameworks for such protection; major issues associated with it; and the need for balancing protection and access in the modern world. The chapter envisages to set a context for the subsequent discussion on major conflicts in implementation of IPR regimes between developed and developing countries.

Genetically Modified Crops, Agriculture and Biosafety

The increasing cultivation of GM crops has raised a wide range of concerns with respect to food safety, environmental effects and socio-economic issues. The chief issue is the threat of introgression of the transgene into natural gene pool. Proponents of GM technology argue on the lines that the technology ensures that farmers get access to higher quality seeds; farm yield is enhanced; varieties with special traits can be created and food security is accomplished. The present chapter discusses the global concerns to GM technology and the governance frameworks namely the Cartagena Protocol on Biosafety and the Nagoya–Kuala Lumpur Supplementary Protocol on Liability and Redress. The status of implementation in various South Asian countries are looked into.

Cross Country Comparisons

The countries that make up the BIMSTEC exhibit several similarities, e.g. rate of economic growth, population, natural resources and so on. In the present chapter, we take a comparative overview of the various IPR treaties and national frameworks concerning natural resources in these seven countries. We specifically cover plant variety protection, traditional knowledge, geographical indications, genetically modified crops and access and benefit sharing.

TRIPS, CBD and Developing Countries: Implications on Food Security and Conservation

The TRIPS and the CBD with their mutually complementary and often conflicting approaches are increasingly shaping the intellectual property rights regimes of the member countries with respect to biological resources. Inclusion of agriculture into the ambit of IPRs has far-reaching consequences for developing countries with respect to food security and natural diversity of plant species. Similarly, implications of IPR in relation to biodiversity, traditional knowledge and indigenous cultural practices are also a matter of great importance. The present chapter discusses the issues related to food security, biodiversity and conservation along with options available under the TRIPS and the CBD with special focus on the concerns of developing countries.