Advanced Glycation End Products and Diabetic Complications

Singh, Varun Parkash,Bali, Anjana,Singh, Nirmal,Jaggi, Amteshwar Singh The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.1

During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed.

A Review on Renal Toxicity Profile of Common Abusive Drugs

Singh, Varun Parkash,Singh, Nirmal,Jaggi, Amteshwar Singh The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

Drug abuse has become a major social problem of the modern world and majority of these abusive drugs or their metabolites are excreted through the kidneys and, thus, the renal complications of these drugs are very common. Morphine, heroin, cocaine, nicotine and alcohol are the most commonly abused drugs, and their use is associated with various types of renal toxicity. The renal complications include a wide range of glomerular, interstitial and vascular diseases leading to acute or chronic renal failure. The present review discusses the renal toxicity profile and possible mechanisms of commonly abused drugs including morphine, heroin, cocaine, nicotine, caffeine and alcohol.

Mechanisms involved in adenosine pharmacological preconditioning-induced cardioprotection

Singh, Lovedeep,Kulshrestha, Ritu,Singh, Nirmal,Jaggi, Amteshwar Singh The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.3

Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury. These mechanisms include activation of $K_{ATP}$ channels, an increase in the levels of antioxidant enzymes, functional interaction with opioid receptors; increase in nitric oxide production; decrease in inflammation; activation of transient receptor potential vanilloid (TRPV) channels; activation of kinases such as protein kinase B (Akt), protein kinase C, tyrosine kinase, mitogen activated protein (MAP) kinases such as ERK 1/2, p38 MAP kinases and MAP kinase kinase (MEK 1) MMP. The present review discusses the role and mechanisms involved in adenosine preconditioning-induced cardioprotection.

Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms

Amritpal Singh Aulakh,Puneet Kaur Randhawa,Nirmal Singh,Amteshwar Singh Jaggi 대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.2

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioninginduced cardioprotection.

Mechanisms involved in adenosine pharmacological preconditioning-induced cardioprotection

Lovedeep Singh,Ritu Kulshrestha,Nirmal Singh,Amteshwar Singh Jaggi 대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.3

Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury. These mechanisms include activation of KATP channels, an increase in the levels of antioxidant enzymes, functional interaction with opioid receptors; increase in nitric oxide production; decrease in inflammation; activation of transient receptor potential vanilloid (TRPV) channels; activation of kinases such as protein kinase B (Akt), protein kinase C, tyrosine kinase, mitogen activated protein (MAP) kinases such as ERK 1/2, p38 MAP kinases and MAP kinase kinase (MEK 1) MMP. The present review discusses the role and mechanisms involved in adenosine preconditioning-induced cardioprotection.

Advanced Glycation End Products and Diabetic Complications

Varun Parkash Singh,Anjana Bali,Nirmal Singh,Amteshwar Singh Jaggi 대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.1

During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts withthe plasma proteins through a non-enzymatic process known as glycation. Protein glycation andformation of advanced glycation end products (AGEs) play an important role in the pathogenesis ofdiabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with someother diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interfereswith their normal functions by disrupting molecular conformation, altering enzymatic activity, andinterfering with receptor functioning. AGEs form intra- and extracellular cross linking not only withproteins, but with some other endogenous key molecules including lipids and nucleic acids to contributein the development of diabetic complications. Recent studies suggest that AGEs interact with plasmamembrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, releaseof pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasmaproteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore,the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract,neuropathy, nephropathy and cardiomyopathy is also discussed.

A Review on Renal Toxicity Profile of Common Abusive Drugs

Varun Parkash Singh,Nirmal Singh,Amteshwar Singh Jaggi 대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

Drug abuse has become a major social problem of the modern world and majority of these abusive drugs or their metabolites are excreted through the kidneys and, thus, the renal complications of these drugs are very common. Morphine, heroin, cocaine, nicotine and alcohol are the most commonly abused drugs, and their use is associated with various types of renal toxicity. The renal complications include a wide range of glomerular, interstitial and vascular diseases leading to acute or chronic renal failure. The present review discusses the renal toxicity profile and possible mechanisms of commonly abused drugs including morphine, heroin, cocaine, nicotine, caffeine and alcohol.

Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms

Aulakh, Amritpal Singh,Randhawa, Puneet Kaur,Singh, Nirmal,Jaggi, Amteshwar Singh The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.2

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (non-cardiac) increases the tolerance of the myocardium to sustained ischemia-reperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

A Review on Chemical-Induced Inflammatory Bowel Disease Models in Rodents

Randhawa, Puneet Kaur,Singh, Kavinder,Singh, Nirmal,Jaggi, Amteshwar Singh The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.4

Ulcerative colitis and Crohn's disease are a set of chronic, idiopathic, immunological and relapsing inflammatory disorders of the gastrointestinal tract referred to as inflammatory bowel disorder (IBD). Although the etiological factors involved in the perpetuation of IBD remain uncertain, development of various animal models provides new insights to unveil the onset and the progression of IBD. Various chemical-induced colitis models are widely used on laboratory scale. Furthermore, these models closely mimic morphological, histopathological and symptomatical features of human IBD. Among the chemical-induced colitis models, trinitrobenzene sulfonic acid (TNBS)-induced colitis, oxazolone induced-colitis and dextran sulphate sodium (DSS)-induced colitis models are most widely used. TNBS elicits Th-1 driven immune response, whereas oxazolone predominantly exhibits immune response of Th-2 phenotype. DSS-induced colitis model also induces changes in Th-1/Th-2 cytokine profile. The present review discusses the methodology and rationale of using various chemical-induced colitis models for evaluating the pathogenesis of IBD.

Effects of Erythropoietin on Memory Deficits and Brain Oxidative Stress in the Mouse Models of Dementia

Rohit Kumar,Nirmal Singh,Amteshwar Singh Jaggi 대한약리학회 2010 The Korean Journal of Physiology & Pharmacology Vol.14 No.5

The present study was undertaken to explore the potential of erythropoietin in memory deficits of mice. Memory impairment was produced by scopolamine (0.5 mg/kg, i.p.) and intracerebroventricular streptozotocin (i.c.v STZ, 3 mg/kg, 10 μl, 1st and 3rd day) in separate groups of animals. Morris watermaze test was employed to assess learning and memory. The levels of brain thio-barbituric acid reactive species (TBARS) and reduced glutathione (GSH) were estimated to assess degree of oxidative stress. Brain acetylcholinesterase enzyme (AChE) activity was also measured. Scopolamine/streptozotocin administration induced significant impairment of learning and memory in mice as indicated by marked decrease in Morris water-maze performance. Scopolamine/streptozotocin administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (an increase in TBARS and a decrease in GSH) levels. Treatment of erythropoietin (500 and 1,000 IU/Kg i.p.) significantly reversed scopolamine- as well as streptozotocin-induced learning and memory deficits along with attenuation of those-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that erythropoietin exerts a beneficial effect in memory deficits of mice possibly through its multiple actions including potential anti-oxidative effect.