Time filter

Source Type

PubMed | University of KwaZulu - Natal and Akal Toxicology Research Center
Type: | Journal: Neuroscience letters | Year: 2016

Clinically, ischemic environment during gynecological surgery at lithotomy position is most common causative factor for the development of vasculitic femoral neuropathy (VFN). The present study was designed to induce the clinically relevant rat model of VFN by ischemic-reperfusion (I/R) injury of unilateral external iliac artery (uEIA). The VFN was induced by 3, 4 and 5h occlusion of uEIA followed by reperfusion. The I/R of uEIA induced VFN was evaluated by (i) behavioral parameters i.e., hind limb temperature; weight bearing capacity; (ii) kinematic analysis i.e., paw posture, splay angle, static sciatic index (SSI), and ankle-angle tests; (iii) evaluation of pain perception i.e., plantar and pin prick; (iv) serum biochemical estimation i.e., nitrate, lipid peroxidation, TNF- and calcium level; (v) evaluation of motor and sensory nerve conduction velocity; and (vi) measurement of nerve fiber density. The 4 and 5h occlusion of uEIA has produced the potential changes in behavioral, functional, electrophysiological, biochemical and histopathological assessment. The 5h occlusion of uEIA has shown to produce the mortality. Whereas, 3h occlusion does not produce the significant changes in the development of VFN. The 4h ischemic occlusion of uEIA has shown potential rat model of VFN due to its close mimicking capacity of VFN in human. Therefore, it can be useful to explore the newer anti-neuralgic medicine and with their pharmacodynamic action in the field of various neurovascular disorders.


Muthuraman A.,Akal Toxicology Research Center | Kaur P.,Akal Toxicology Research Center
Current Drug Targets | Year: 2016

Renin-Angiotensin-Aldosterone System (RAAS) is well established in renovascular and cardiovascular functions. The modulators of this system are significantly used for regulating elevated blood pressure in human and animals. Recently, it has also been documented to produce neurological actions. The abnormalities of this system raise renin, angiotensin (AT), angiotensin converting enzyme (ACE) activity, and aldosterone in circulation and nerve tissues. In the nervous system, abundant rise of these components cause neuronal damage and neurodegeneration. ACE contributes to degradation of β-amyloid in the brain, that is responsible for Alzheimer disease (AD). But, angiotensin converting enzyme-2 (ACE-2) mediated release of angiotensin1-7 (AT1-7) peptide in nerve tissue has potential neuroprotective actions. This review focuses on the current perspectives of the RAAS in neurodegeneration along with possible cellular and molecular mechanisms. Also, we have discussed the current evidence of RAAS modulators in the management of neuropathic pain in human and animals. Thus, we believe that, in the future, RAAS modulators may play a great role in the management of neuropathic pain and other neurodegenerative disorders such as AD, Parkinson disease (PD) and amyotrophic lateral sclerosis. But, more extensive clinical research is required for utilizing RAAS modulators in neurode-generative disorders. © 2016 Bentham Science Publishers.


Muthuraman A.,Akal Toxicology Research Center | Kaur P.,Akal Toxicology Research Center | Singh H.,Akal Toxicology Research Center | Boparai P.S.,Akal Toxicology Research Center
Life Sciences | Year: 2015

Aims The present study has been designed to investigate the ameliorative potential of vitamin P, and digoxin in ischemic-reperfusion (I/R)-induced renal injury in isolated rat kidney preparations by using the Langendorff apparatus. Main methods Vitamin P (50 and 100 mg/kg; p.o.) was administered to rats for 5 consecutive days. On the 6th day, isolated kidneys were subjected to 30 min of ischemia followed by 120 min of reperfusion by constant flow (8 ml/min). The total renal effluent was collected at various time intervals (i.e., basal, 0, 15, 30, 45 and 60 min). In addition, urea, creatinine, and creatine kinase (CK) activity were evaluated in the renal effluent, and TBARS, GSH, and Na+-K+-ATPase activity were evaluated in tissue. Key findings I/R of renal tissue produced a rise in the activity of CK and the levels of urea and creatinine in the renal effluent, as well as in the activity of Na+-K+-ATPase and levels of TBARS in the tissue. Additionally, it decreased GSH levels when compared with the sham control group. Digoxin served as positive control in the present work. Treatment with vitamin P (100 mg/kg), and digoxin (500 μg/kg) produced a significant (P < 0.05) ameliorative effect against the I/R induced changes in biomarkers. Significance The renoprotective effect of vitamin P is caused by its inhibition of Na+-K+-ATPase activity, which subsequently results in free radical scavenging and anti-infarct properties. Therefore, this vitamin can be useful in the management of renovascular disorders. © 2015 Elsevier Inc. All rights reserved.


PubMed | Akal Toxicology Research Center
Type: Journal Article | Journal: Current drug targets | Year: 2016

Renin-Angiotensin-Aldosterone System (RAAS) is well established in renovascular and cardiovascular functions. The modulators of this system are significantly used for regulating elevated blood pressure in human and animals. Recently, it has also been documented to produce neurological actions. The abnormalities of this system raise renin, angiotensin (AT), angiotensin converting enzyme (ACE) activity, and aldosterone in circulation and nerve tissues. In the nervous system, abundant rise of these components cause neuronal damage and neurodegeneration. ACE contributes to degradation of -amyloid in the brain, that is responsible for Alzheimer disease (AD). But, angiotensin converting enzyme-2 (ACE-2) mediated release of angiotensin1-7 (AT1-7) peptide in nerve tissue has potential neuroprotective actions. This review focuses on the current perspectives of the RAAS in neurodegeneration along with possible cellular and molecular mechanisms. Also, we have discussed the current evidence of RAAS modulators in the management of neuropathic pain in human and animals. Thus, we believe that, in the future, RAAS modulators may play a great role in the management of neuropathic pain and other neurodegenerative disorders such as AD, Parkinson disease (PD) and amyotrophic lateral sclerosis. But, more extensive clinical research is required for utilizing RAAS modulators in neurodegenerative disorders.


PubMed | Akal Toxicology Research Center
Type: Journal Article | Journal: Naunyn-Schmiedeberg's archives of pharmacology | Year: 2015

Ischemic-reperfusion (I/R) is a major event in the pathogenesis of ischemic heart disease that leads to higher rate of mortality. The study has been designed to investigate the therapeutic potential and molecular mechanism of vitamin P and digoxin in I/R-induced myocardial infarction in isolated rat heart preparation by using Langendorff apparatus. The animals were treated with vitamin P (50 and 100mg/kg; p.o.) and digoxin (500g/kg) for 5 consecutive days. Digoxin served as a positive control in the present study. On the sixth day, the heart was harvested and induced to 30min of global ischemia followed by 120min of reperfusion using Langendorff apparatus. The coronary effluent was collected at different time intervals (i.e. basal, 1, 15, 30, 45, 60 and 120min.) for the assessment of myocardial contractility function. In addition, creatine kinase-M and B subunits (CK-MB), lactate dehydrogenase (LDH1) and Na(+)-K(+)-ATPase activity along with oxidative tissue biomarkers (i.e. thio-barbituric acid reactive substances (TBARS) and reduced glutathione (GSH)) changes were estimated. The I/R of myocardium produced decrease in coronary flow rate; increase in CK-MB, LDH1 and Na(+)-K(+)-ATPase activity along with increase in TBARS and decrease in GSH levels as compared to normal group. The treatment with vitamin P (100mg/kg) and digoxin (500g/kg) have produced a significant (p<0.05) ameliorative effect against I/R induced above functional, metabolic and tissue biomarkers changes. Vitamin P has an ameliorative potential against I/R induced myocardial functional changes. It may be due to its free radical scavenging and anti-infarct property via inhibition of Na(+)-K(+)-ATPase activity. Therefore, it can be used as a potential therapeutic medicine for the management of cardiovascular disorders.

Loading Akal Toxicology Research Center collaborators
Loading Akal Toxicology Research Center collaborators