Vijay Chauthaiwale

Chronic overnutrition and consequential visceral obesity is associated with a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. Moreover, individuals who have a triad of hypertension, dysglycemia, and elevated triglycerides along with reduced high-density lipoprotein cholesterol have a greater residual cardiovascular risk even after factoring for the traditional risk factors such as age, smoking, diabetes, and elevated low-density lipoprotein cholesterol. In our… Show more

Chronic overnutrition and consequential visceral obesity is associated with a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. Moreover, individuals who have a triad of hypertension, dysglycemia, and elevated triglycerides along with reduced high-density lipoprotein cholesterol have a greater residual cardiovascular risk even after factoring for the traditional risk factors such as age, smoking, diabetes, and elevated low-density lipoprotein cholesterol. In our previous study we demonstrated that TRC150094, when administered to rats receiving a high-fat diet, stimulated mitochondrial fatty acid oxidation (FAO) and reduced visceral adiposity, opening an interesting perspective for a possible clinical application. In the present study, oral administration of TRC150094 to obese Zucker spontaneously hypertensive fatty rats (obese ZSF1) improved glucose tolerance and glycemic profile as well as attenuated a rise in blood pressure. Obese ZSF1 rats treated with TRC150094 also showed reduced hepatic steatosis, reduced progression of nephropathy, and improved skeletal muscle function. At the cellular level, TRC150094 induced a significant increase in mitochondrial respiration as well as an increased FAO in liver and skeletal muscle, ultimately resulting in reduced hepatic as well as total body fat accumulation, as evaluated by magnetic resonance spectroscopy and magnetic resonance imaging, respectively. If reproduced in humans, these results could confirm that TRC150094 may represent an attractive therapeutic agent to counteract multiple residual cardiovascular risk components.
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Induction of HSPs is a natural response of stressed cells that protects against many insults including acute ischemia. TRC051384, a novel compound belonging to substituted 2-propen-1-one class is a potent inducer of heat shock protein 70 (HSP70). The aim of this study was to investigate the ability of TRC051384 in reducing neuronal injury and disability upon delayed treatments (4 and 8hours post ischemia onset) in a rat model of transient cerebral ischemia. Focal cerebral ischemia was produced… Show more

Induction of HSPs is a natural response of stressed cells that protects against many insults including acute ischemia. TRC051384, a novel compound belonging to substituted 2-propen-1-one class is a potent inducer of heat shock protein 70 (HSP70). The aim of this study was to investigate the ability of TRC051384 in reducing neuronal injury and disability upon delayed treatments (4 and 8hours post ischemia onset) in a rat model of transient cerebral ischemia. Focal cerebral ischemia was produced in rats by occluding the MCA using the intra luminal suture technique. Rats subjected to 2hours focal cerebral ischemia were administered by intra-peritoneal route, TRC051384 or vehicle every 2hours for 48hours, from 4th hour or 8th hour after onset of ischemia. Progression of infarct and edema was assessed up to 48hours post ischemic insult using magnetic resonance imaging and the neurological disability and survival studied till 7 days. Here we show for the first time that treatment with TRC051384 significantly reduces stroke associated neuronal injury (87% reduction in area of penumbra recruited to infarct, and 25% reduction in brain edema) and disability in a rat model of transient ischemic stroke even when administered 8hours post onset of ischemia. Significant improvement in survival (50% by day2 and 67.3% by day 7) was observed with TRC051384 treatment initiated at 4hours after ischemia onset. Induction of HSP70 by TRC051384 involves HSF1 activation and results in elevated chaperone and anti-inflammatory activity. These results show that TRC051384 has the potential to be developed as a novel pharmacological agent for the treatment of ischemic stroke Show less