Pallu Reddanna

Bio: Pallu Reddanna is an academic researcher from University of Hyderabad. The author has contributed to research in topics: Arachidonic acid & Lipoxygenase. The author has an hindex of 43, co-authored 190 publications receiving 5909 citations. Previous affiliations of Pallu Reddanna include Sri Venkateswara University & Yahoo!.

Eicosanoids in inflammation and cancer: the role of COX-2

Abstract: Eicosanoids, a family of oxygenated metabolites of eicosapolyenoic fatty acids, such as arachidonic acid, formed via the lipoxygenase, cyclooxygenase (COX) and epoxygenase pathways, play an important role in the regulation of various pathophysiological processes, including inflammation and cancer. COX-2, the inducible isoform of COX, has emerged as the key enzyme regulating inflammation, and promises to play a considerable role in cancer. Although NSAIDs have been in use for centuries, the COX-2 selective inhibitors - coxibs - have emerged as potent anti-inflammatory drugs with fewer gastric side effects. As COX-2 plays a major role in neoplastic transformation and cancer growth, by downregulating apoptosis and promoting angiogenesis, invasion and metastasis, coxibs have a potential role in the prevention and treatment of cancer. Recent studies indicate their possible application in overcoming drug resistance by downregulating the expression of MDR-1. However, the cardiac side effects of some of the coxibs have limited their application in treating various inflammatory disorders and warrant the development of COX-2 inhibitors without side effects. This review will focus on the role of COX-2 in inflammation and cancer, with an emphasis on novel approaches to the development of COX-2 inhibitors without side effects.

Fulminant Hepatic Failure in Rats Induces Oxidative Stress Differentially in Cerebral Cortex, Cerebellum and Pons Medulla

Abstract: Hepatic Encephalopathy (HE) is one of the most common complications of acute liver diseases and is known to have profound influence on the brain. Most of the studies, available from the literature are pertaining to whole brain homogenates or mitochondria. Since brain is highly heterogeneous with functions localized in specific areas, the present study was aimed to assess the oxidative stress in different regions of brain-cerebral cortex, cerebellum and pons medulla during acute HE. Acute liver failure was induced in 3-month old adult male Wistar rats by intraperitoneal injection of thioacetamide (300 mg/kg body weight for two days), a well known hepatotoxin. Oxidative stress conditions were assessed by free radical production, lipid peroxidation, nitric oxide levels, GSH/GSSG ratio and antioxidant enzyme machinery in three distinct structures of rat brain-cerebral cortex, cerebellum and pons medulla. Results of the present study indicate a significant increase in malondialdehyde (MDA) levels, reactive oxygen species (ROS), total nitric oxide levels [(NO) estimated by measuring (nitrites + nitrates)] and a decrease in GSH/GSSG ratio in all the regions of brain. There was also a marked decrease in the activity of the antioxidant enzymes-glutathione peroxidase, glutathione reductase and catalase while the super oxide dismutase activity (SOD) increased. However, the present study also revealed that pons medulla and cerebral cortex were more susceptible to oxidative stress than cerebellum. The increased vulnerability to oxidative stress in pons medulla could be due to the increased NO levels and increased activity of SOD and decreased glutathione peroxidase and glutathione reductase activities. In summary, the present study revealed that oxidative stress prevails in different cerebral regions analyzed during thioacetamide-induced acute liver failure with more pronounced effects on pons medulla and cerebral cortex.

The role of vitamin E and selenium on arachidonic acid oxidation by way of the 5-lipoxygenase pathway.

Abstract: Arachidonic acid, the most abundant Go polyunsaturated fatty acid found in the phospholipids of mammalian tissues, is a biosynthetic precursor of several families of compounds that exert diverse biological effects. Once the action of phospholipases releases arachidonic acid from phospholipids, it is metabolized by one of the two pathways shown in FIGURE 1. The cyclooxygenase pathway produces prostaglandins (PG), thromboxanes (TX), and prostacyclins (PGI), whereas the lipoxygenase pathway leads to the formation of leukotrienes (LT) and lipoxins. The enzymic oxidation of arachidonic acid by way of the cyclooxygenase and lipoxygenase pathways to produce a spectrum of biologically active compounds is collectively referred to as the arachidonic acid cascade. Recent attention has focused on those factors that can regulate the concentration of these biologically active eicosanoids, especially in relation to their possible role in several pathological conditions including arteriosclerosis, arthritis, asthma, and anaphylactic reactions.'-3 One area of particular interest has been the effect of fatty acid hydroperoxides (FAHP) on lipoxygenase and cyclooxygenase activities. For example, both cyclooxygenase and lipoxygenase exhibit an obligatory requirement for FAHP ( < 1 pM) as an activator; however, these enzymes are inhibited by higher concentrations (> 10 pM) of FAHP.\"' The interest in FAHP, as modulators of the arachidonic acid cascade, probably reflects the implication of lipid peroxidation, one of the possible sources of FAHP formation, in many pathological and nonpathological in vivo processes.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

Abstract: Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.

The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.

Abstract: The glutathione S-transferases (GST) represent a major group of detoxification enzymes. All eukaryotic species possess multiple cytosolic and membrane-bound GST isoenzymes, each of which displays distinct catalytic as well as noncatalytic binding properties: the cytosolic enzymes are encoded by at least five distantly related gene families (designated class alpha, mu, pi, sigma, and theta GST), whereas the membrane-bound enzymes, microsomal GST and leukotriene C, synthetase, are encoded by single genes and both have arisen separately from the soluble GST. Evidence suggests that the level of expression of GST is a crucial factor in determining the sensitivity of cells to a broad spectrum of toxic chemicals. In this article the biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress.A description of the mechanisms of transcriptional and posttranscriptional regulat...