1.Acute and sub-acute oral toxicity profile of Acorus calamus (Sweet flag) in rodents
Arunachalam MUTHURAMAN ; Nirmal SINGH
Asian Pacific Journal of Tropical Biomedicine 2012;(z2):1017-1023
Objective: To determine the acute and sub-acute oral toxicity profile of the hydroalcoholic extract of Acorus calamus (HAE-AC) in mice and rats respectively. Methods: In acute toxicity study, mice were assessed to any alteration of general behavior and mortality rate within 24 h. Further, in sub-acute toxicity study, rats were used for assessment of mortality, body weight, hematological, biochemical and histopathological changes. Results: Single oral administrations of the HAE-AC 2500-10000 mg/kg induced increase in general behavioral abnormalities in mice. The mortality rate also increased with increasing dosage (median lethal dose; LD50 = 5 070.59 mg/kg). Daily single oral doses of HAE-AC 200, 500 and 1 000 mg/kg were observed to be well tolerated behaviorally after 28 days of dosing and induced no significant changes in body and organs weights of rats. Further, a mild rise in the levels of alanine transaminase (ALT), aspartate transaminase (AST) and histopatholological changes in liver tissue was noted at 1000 mg/kg dose of HAE-AC. Conclusions: Overall, the findings of this study indicate that, HAE-AC is non-toxic and has at high dose, a mild but acceptable toxicity potential.
2.Plant profile, phytochemistry and pharmacology of Avartani (Helicteres isora Linn.):A review
Kumar Nirmal ; Singh Kumar Anil
Asian Pacific Journal of Tropical Biomedicine 2014;(z1):22-26
Plants are used as medicine since ancient time, in organized (Ayurveda, Unani & Siddha) and unorganized (folk, native & tribal) form. In these systems, drugs are described either in Sanskrit or vernacular languages. Avartani (Helicteres isora Linn.) is a medicinal plant which is used in several diseases. It is commonly known as Marodphali, Marorphali, Enthani etc. due to screw like appearance of its fruit. Avartani is used as a folk medicine to treat snake bite, diarrhoea and constipation of new born baby. In the research, antioxidant, hypolipidaemic, antibacterial and antiplasmid activities, cardiac antioxidant, antiperoxidative potency, brain-antioxidation potency, anticancer activity, antinociceptive activity, hepatoprotective activity, anti-diarrheal activity and wormicidal activity in this plant were reviewed.
3.A Review on Renal Toxicity Profile of Common Abusive Drugs.
Varun Parkash SINGH ; Nirmal SINGH ; Amteshwar Singh JAGGI
The Korean Journal of Physiology and Pharmacology 2013;17(4):347-357
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.
Caffeine
;
Cocaine
;
Heroin
;
Kidney
;
Kidney Failure, Chronic
;
Morphine
;
Nicotine
;
Renal Insufficiency
;
Social Problems
;
Substance-Related Disorders
;
Vascular Diseases
4.Effect of Neurosteroid Modulation on Global Ischaemia-Reperfusion-Induced Cerebral Injury in Mice.
Amarjot Kaur GREWAL ; Amteshwar Singh JAGGI ; Avtar Chand RANA ; Nirmal SINGH
The Korean Journal of Physiology and Pharmacology 2013;17(6):485-491
The present study was designed to investigate the putative effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion followed by reperfusion, produced a significant rise in cerebral infarct size along with impairment of grip strength and motor coordination in Swiss albino mice. Administration of carbamazepine (16 mg/kg, i.p.) before global cerebral ischaemia significantly attenuated cerebral infarct size and improved the motor performance. However, administration of indomethacin (100 mg/kg, i.p.) attenuated the neuroprotective effect of carbamazepine. Mexiletine (50 mg/kg, i.p.) did not produce significant neuroprotective effect. It may be concluded that the neuroprotective effect of carbamazepine may be due to increase in synthesis of neurosteroids perhaps by activating enzyme (3alpha HSD) as indomethacin attenuated the neuroprotective effect of carbamazepine. The sodium channel blocking effect of carbamazepine may not be involved in neuroprotection as mexiletine, a sodium channel blocker, did not produce significant neuroprotective effect.
Animals
;
Carbamazepine
;
Carotid Arteries
;
Hand Strength
;
Indomethacin
;
Mexiletine
;
Mice*
;
Neuroprotective Agents
;
Neurotransmitter Agents
;
Reperfusion
;
Sodium Channels
5.A Review on Chemical-Induced Inflammatory Bowel Disease Models in Rodents.
Puneet Kaur RANDHAWA ; Kavinder SINGH ; Nirmal SINGH ; Amteshwar Singh JAGGI
The Korean Journal of Physiology and Pharmacology 2014;18(4):279-288
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.
Acetic Acid
;
Colitis
;
Colitis, Ulcerative
;
Crohn Disease
;
Dextrans
;
Gastrointestinal Tract
;
Humans
;
Inflammatory Bowel Diseases*
;
Models, Animal
;
Oxazolone
;
Phenotype
;
Rodentia*
;
Sodium
6.Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms.
Amritpal Singh AULAKH ; Puneet Kaur RANDHAWA ; Nirmal SINGH ; Amteshwar Singh JAGGI
The Korean Journal of Physiology and Pharmacology 2017;21(2):145-152
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 preconditioning-induced cardioprotection.
Brain
;
Femoral Nerve
;
Hexamethonium
;
Ischemic Preconditioning*
;
Myocardium
;
Negotiating
;
Nerve Endings
;
Neurons
;
Sciatic Nerve
;
Sensory Receptor Cells
;
Trimethaphan
;
Vagus Nerve
7.Mechanisms involved in adenosine pharmacological preconditioning-induced cardioprotection.
Lovedeep SINGH ; Ritu KULSHRESTHA ; Nirmal SINGH ; Amteshwar Singh JAGGI
The Korean Journal of Physiology and Pharmacology 2018;22(3):225-234
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.
Adenosine Triphosphate
;
Adenosine*
;
Heart
;
Inflammation
;
Mitogen-Activated Protein Kinase Kinases
;
Nitric Oxide
;
Phosphotransferases
;
Protein Kinase C
;
Protein-Tyrosine Kinases
;
Proto-Oncogene Proteins c-akt
;
Receptors, Opioid
;
Receptors, Purinergic P1
;
Reperfusion Injury
8.Advanced Glycation End Products and Diabetic Complications.
Varun Parkash SINGH ; Anjana BALI ; Nirmal SINGH ; Amteshwar Singh JAGGI
The Korean Journal of Physiology and Pharmacology 2014;18(1):1-14
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.
Aging
;
Arthritis, Rheumatoid
;
Blood Proteins
;
Cardiomyopathies
;
Cataract
;
Cell Membrane
;
Collagen
;
Diabetes Complications*
;
Diabetes Mellitus
;
Fibrinogen
;
Free Radicals
;
Gene Expression
;
Globulins
;
Glucose
;
Glycosylation End Products, Advanced*
;
Inflammation
;
Molecular Conformation
;
Nucleic Acids
;
Osteoporosis
;
Oxidative Stress
9.Animals models of spinal cord contusion injury
Renuka VERMA ; Jasleen Kaur VIRDI ; Nirmal SINGH ; Amteshwar Singh JAGGI
The Korean Journal of Pain 2019;32(1):12-21
Spinal cord contusion injury is one of the most serious nervous system disorders, characterized by high morbidity and disability. To mimic spinal cord contusion in humans, various animal models of spinal contusion injury have been developed. These models have been developed in rats, mice, and monkeys. However, most of these models are developed using rats. Two types of animal models, i.e. bilateral contusion injury and unilateral contusion injury models, are developed using either a weight drop method or impactor method. In the weight drop method, a specific weight or a rod, having a specific weight and diameter, is dropped from a specific height on to the exposed spinal cord. Low intensity injury is produced by dropping a 5 g weight from a height of 8 cm, moderate injury by dropping 10 g weight from a height of 12.5–25 mm, and high intensity injury by dropping a 25 g weight from a height of 50 mm. In the impactor method, injury is produced through an impactor by delivering a specific force to the exposed spinal cord area. Mild injury is produced by delivering 100 ± 5 kdyn of force, moderate injury by delivering 200 ± 10 kdyn of force, and severe injury by delivering 300 ± 10 kdyn of force. The contusion injury produces a significant development of locomotor dysfunction, which is generally evident from the 0–14(th) day of surgery and is at its peak after the 28–56th day. The present review discusses different animal models of spinal contusion injury.
Animals
;
Body Weight
;
Cervical Vertebrae
;
Contusions
;
Female
;
Haplorhini
;
Humans
;
Locomotion
;
Methods
;
Mice
;
Models, Animal
;
Nervous System Diseases
;
Rats
;
Spinal Cord Injuries
;
Spinal Cord
10.An integrated review on new targets in the treatment of neuropathic pain.
Ravneet Kaur KHANGURA ; Jasmine SHARMA ; Anjana BALI ; Nirmal SINGH ; Amteshwar Singh JAGGI
The Korean Journal of Physiology and Pharmacology 2019;23(1):1-20
Neuropathic pain is a complex chronic pain state caused by the dysfunction of somatosensory nervous system, and it affects the millions of people worldwide. At present, there are very few medical treatments available for neuropathic pain management and the intolerable side effects of medications may further worsen the symptoms. Despite the presence of profound knowledge that delineates the pathophysiology and mechanisms leading to neuropathic pain, the unmet clinical needs demand more research in this field that would ultimately assist to ameliorate the pain conditions. Efforts are being made globally to explore and understand the basic molecular mechanisms responsible for somatosensory dysfunction in preclinical pain models. The present review highlights some of the novel molecular targets like D-amino acid oxidase, endoplasmic reticulum stress receptors, sigma receptors, hyperpolarization-activated cyclic nucleotide-gated cation channels, histone deacetylase, Wnt/β-catenin and Wnt/Ryk, ephrins and Eph receptor tyrosine kinase, Cdh-1 and mitochondrial ATPase that are implicated in the induction of neuropathic pain. Studies conducted on the different animal models and observed results have been summarized with an aim to facilitate the efforts made in the drug discovery. The diligent analysis and exploitation of these targets may help in the identification of some promising therapies that can better manage neuropathic pain and improve the health of patients.
Adenosine Triphosphatases
;
Chronic Pain
;
Cyclic Nucleotide-Gated Cation Channels
;
Drug Discovery
;
Endoplasmic Reticulum Stress
;
Ephrins
;
Histone Deacetylases
;
Humans
;
Models, Animal
;
Nervous System
;
Neuralgia*
;
Oxidoreductases
;
Receptors, Eph Family
;
Receptors, sigma