Pragasam Viswanathan

Renoprotective effect of aged garlic extract in streptozotocin- induced diabetic rats

Objective: Aged garlic extract (AGE) has been proven to exhibit antioxidant, hypolipidemic, hypoglycemic and antidiabetic properties. However, its effect on diabetic nephropathy was unexplored. Therefore, the present study was designed to investigate the renoprotective effect of AGE in streptozotocin-induced diabetic rats. Materials and Methods: Albino Wistar rats were induced with diabetes by a single intraperitoneal injection of 45 mg/kg b.w. of streptozotocin. Commercially available AGE was supplemented orally at a dose of 500 mg/kg body weight/day. Aminoguanidine, which has been proven to be an anti-glycation agent was used as positive control and was supplemented at a dose of 1 g/L in drinking water. The serum and urinary biochemical parameters were analyzed in all the groups and at the end of 12 weeks follow up, the renal histological examination were performed using H & E and PAS staining. Results: The diabetic rats showed a significant change in the urine (P < 0.001) and serum (P < 0.01) constituents such as albumin, creatinine, urea nitrogen and glycated hemoglobin. In addition, the serum lipid profile of the diabetic rats were altered significantly (P < 0.05) compared to that of the control rats. However, the diabetic rats supplemented with aged garlic extract restored all these biochemical changes. The efficacy of the extract was substantiated by the histopathological changes in the kidney. Conclusion: From our results, we conclude that aged garlic extract has the ability to ameliorate kidney damage in diabetic rats and the renoprotective effect of AGE may be attributed to its anti-glycation and hypolipidemic activities.

Soluble CD36 in plasma and urine: A plausible prognostic marker for diabetic nephropathy

AIMS This study was designed to analyze the level of soluble CD36 (sCD36) in both plasma and urine of type 2 diabetic patients with and without microalbuminuria/macroalbuminuria. METHODS Study subjects (n=20 each) comprised of those with normal glucose tolerance, type 2 diabetes (T2DM) with normoalbuminiria, T2DM with microalbuminuria and T2DM with macroalbuminuria. The biochemical parameters were analyzed using auto-analyzer, and the level of sCD36 was estimated using an in-house Sandwich ELISA. RESULTS The presence of sCD36 has been identified for the first time in the urine sample. Significant increase in the level of sCD36 was observed in both plasma and urine of diabetic patients with microalbuminuria (P<0.01) and macroalbuminuria (P<0.001). Positive correlation of sCD36 with the kidney markers such as urea, creatinine and eGFR confirmed the association of sCD36 with kidney damage in diabetic patients. Microalbuminuria, which is clinically used as a biomarker for nephropathy showed a strong positive correlation with urine sCD36 (r=0.642; P<0.001) and plasma sCD36 (r=0.498; P<0.001) in Pearson correlation analysis, which was further substantiated in stepwise multiple regression analysis. CONCLUSIONS Our study implies a plausible prognostic/adjuvant biomarker role of soluble CD36 for diabetic nephropathy.

Eugenol exhibits anti-virulence properties by competitively binding to quorum sensing receptors

Abstract The primary objective of this study was to ascertain the anti-biofilm and anti-virulence properties of sub-minimum inhibitory concentration (MIC) levels of eugenol against the standard strain PAO1 and two multi-drug resistant P. aeruginosa clinical isolates utilizing quorum sensing inhibition (QSI). Eugenol at 400 μM significantly reduced biofilm formation on urinary catheters and the virulence factors (VF) including extracellular polysaccharides, rhamnolipid, elastase, protease, pyocyanin, and pyoverdine (p < 0.001). Further, eugenol exhibited a marked effect on the production of QS signals (AIs) (p < 0.001) without affecting their chemical integrity. In silico docking studies demonstrated a stable molecular binding between eugenol and QS receptor(s) in comparison with respective AIs. Investigation on reporter strains confirmed the competitive binding of eugenol to a QS receptor (LasR) as the possible QSI mechanism leading to significant repression of QS associated genes besides the VF genes (p < 0.001). This study provides insights, for the first time, into the mechanism of the anti-virulence properties of eugenol.

Diabetic Cardiomyopathy: A New Perspective of Mechanistic Approach

Diabetic cardiomyopathy (DCM), one among the macrovascular complications of diabetes is the leading cause of mortality around the globe. The emergence of DCM irrespective of other cardiovascular diseases (CVD) necessitates a deeper insight into its occurrence and mechanism of development. This review summarizes the different stages in DCM progression based on molecular, cellular and functional level. The early stage in DCM involves oxidative stress and endoplasmic reticulum stress concomitant with O-linked glycosylation of receptors, and extracellular matrix (ECM) proteins, and formation of advanced glycation end products (AGE). This further influences myocyte apoptosis and steatosis, which is followed by fibrosis and remodeling, thus altering the physiological functioning of heart. It has been postulated that, microbuminuria (MA) which is an indicator of renal failure is also an early predictor of DCM. Currently, focus on epigenetic modifications, as observed in diabetics with renal failure is of critical importance to unveil the mystery behind the association of DCM and MA. Albeit, we examine DCM in a mechanistic approach, the major reason that remains unnoticed is glycemic excursion (GE). ACCORD, DCCT and EDIC studies have reported that the persistent effect in CVD is due to transient hyperglycemia . Hence it is predicted that, treatment strategies focusing on genetic level, along with maintaining persistent blood glucose would be more effectual. Besides, designing treatment regimen for patients with renal failure would be a preventive strategy for diabetic cardiomyopathy when their state towards DCM incidence is also considered and monitored precisely.

Plant Quorum Sensing Inhibitors: Food, Medicinal Plants, and Others

Plants living in an environment with high bacterial density were long suspected to have protective mechanisms against infections. Due to this reason, natural products were explored initially because of their broad therapeutic values in traditional medical practice. Since these plants can be consumed by humans, the active compounds that are having therapeutic activities should be safe toward human cells. However, as science progressed, toxicological studies were performed on these active compounds to avoid their toxicity. The interest to identify and understand the biological functions and the mode of action responsible for their therapeutic roles has been escalated. To date, biologically active constituents of natural products, especially plant-derived ones, have led to the discovery of new drugs used for the treatment of numerous diseases. However, the absence of an immune system in plants, unlike humans and animals against the invaders, demanded researchers to speculate other defense mechanisms to defeat the pathogens (Koh et al. 2013), and manipulation of quorum sensing (QS) systems is considered to be a mode of defense by the plants against pathogens.

Methylation-Demethylation Dynamics: Implications of Changes in Acute Kidney Injury

Over the years, the epigenetic landscape has grown increasingly complex. Until recently, methylation of DNA and histones was considered one of the most important epigenetic modifications. However, with the discovery of enzymes involved in the demethylation process, several exciting prospects have emerged that focus on the dynamic regulation of methylation and its crucial role in development and disease. An interplay of the methylation-demethylation machinery controls the process of gene expression. Since acute kidney injury (AKI), a major risk factor for chronic kidney disease and death, is characterised by aberrant expression of genes, understanding the dynamics of methylation and demethylation will provide new insights into the intricacies of the disease. Research on epigenetics in AKI has only made its mark in the recent years but has provided compelling evidence that implicates the involvement of methylation and demethylation changes in its pathophysiology. In this review, we explore the role of methylation and demethylation machinery in cellular epigenetic control and further discuss the contribution of methylomic changes and histone modifications to the pathophysiology of AKI.

Challenges in oral drug delivery: a nano-based strategy to overcome

Oral drug delivery (ODD) is the most preferred and convenient route of drug administration due to high patient compliance, cost-effectiveness, least sterility constraints, flexibility in the design of dosage form and ease of production. However, the challenges faced in oral drug delivery include poor bioavailability of drug, which is determined by three vital factors, namely, dissolution, permeability, and solubility. In order to achieve effective drug absorption in vivo, various mathematical models have been designed to predict the dissolution and solubility rate of drug. Likewise, permeability is determined by cellular and noncellular models. In addition, behavior of the drug in gastrointestinal tract (GIT) is dependent on intrinsic factors of drug and physiological aspects, namely, pH, microbial colonization, and enzymes. Several pharmaceutical techniques have been contrived to stabilize and solubilize the active compounds in GIT, but it failed to attain a controlled and targeted release of the oral drug. This chapter overviews the strategy to override such drawbacks by ushering in various nanotechnology platforms like polymer based nanocarriers, lipid based nanocarriers, metal, and inorganic-based nanoparticles.

Quorum Sensing in Pathogenesis and Virulence

The bacterial species have co-evolved with the human race and account for more than 3,000 distinct species of which most are beneficial to the humans. They are a few micrometres in length and outnumber the eukaryotic cells by a ratio of 10,000:1. They have evolved their own strategies for countering the defences of the human host. Pathogenicity of microorganisms is through the expression of the virulence factors, which could be attributed to their genetic or biochemical or structural features, which are responsible for the organism to cause an infection in the host (Oelschlaeger et al. 2002). The dynamic relationship between the host and pathogen is an outcome of the virulence of the pathogen and the resistance or susceptibility of the host to the invading pathogen (Casadevall and Pirofski 2000).