Preventive Action of Beta-Carotene against the Indoxyl Sulfate-Induced Renal Dysfunction in Male Adult Zebrafish via Regulations of Mitochondrial Inflammatory and ß-Carotene Oxygenase-2 Actions.

Indoxyl sulfate (IS) is a metabolic byproduct of indole metabolism. IS readily interacts with the mitochondrial redox metabolism, leading to altered renal function. The ß-carotene oxygenase-2 (BCO2) enzyme converts carotenoids to intermediate products. However, the role of ß-carotene (BC) in IS-induced renal dysfunction in zebrafish and their modulatory action on BCO2 and mitochondrial inflammations have not been explored yet. Hence, the present study is designed to investigate the role of BC in the attenuation of IS-induced renal dysfunction via regulations of mitochondrial redox balance by BCO2 actions. Renal dysfunction was induced by exposure to IS (10 mg/L/hour/day) for 4 weeks. BC (50 and 100 mg/L/hour/day) and coenzyme Q10 (CoQ10; 20 mg/L/hour/day) were added before IS exposure. BC attenuated the IS-induced increase in blood urea nitrogen (BUN) and creatinine concentrations, adenosine triphosphate (ATP), and complex I activity levels, and the reduction of renal mitochondrial biomarkers, i.e., BCO2, superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (GPX1), reduced and oxidized glutathione (GSH/GSSG) ratio, and carbonylated proteins. Moreover, renal histopathological changes were analyzed by the eosin and hematoxylin staining method. As a result, the administration of BC attenuated the IS-induced renal damage via the regulation of mitochondrial function.

Therapeutic Investigation of Palm Oil Mill Effluent-Derived Beta-Carotene in Streptozotocin-Induced Diabetic Retinopathy via the Regulation of Blood-Retina Barrier Functions.

Diabetic retinopathy (DR) primarily progresses into retinal degeneration caused by microvascular dysfunction. The pathophysiology of DR progression is still uncertain. This study investigates the function of beta-carotene (PBC) originating from palm oil mill effluent in the treatment of diabetes in mice. An intraperitoneal injection of streptozotocin (35 mg/kg) was used to induce diabetes, which was then accelerated by an intravitreal (i.vit.) injection of STZ (20 µL on day 7). PBC (50 and 100 mg/kg) and dexamethasone (DEX: 10 mg/kg) were also administered orally (p.o.) for 21 days. At various time intervals, the optomotor response (OMR) and visual-cue function test (VCFT) responses were evaluated. Biomarkers, such as reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARSs), and catalase activity were determined in retinal tissue samples. DR significantly lowers the spatial frequency threshold (SFT) and time spent in the target quadrant (TSTQ), increases the reaching time in the visual-cue platform (RVCP), lowers retinal GSH and catalase activity levels, and elevates TBARS levels. The treatments of PBC and DEX also ameliorate STZ-induced DR alterations. The potential ameliorative activity of PBC in DR is attributed to its anti-diabetic, anti-oxidative, and control of blood-retinal barrier layer properties.

Palm Oil Derived Tocotrienol-Rich Fraction Attenuates Vascular Dementia in Type 2 Diabetic Rats.

Vascular dementia (VaD) is a serious global health issue and type 2 diabetes mellitus (T2DM) patients are at higher risk. Palm oil tocotrienol-rich fraction (TRF) exhibits neuroprotective properties; however, its effect on VaD is not reported. Hence, we evaluated TRF effectiveness in T2DM-induced VaD rats. Rats were given a single dose of streptozotocin (STZ) and nicotinamide (NA) to develop T2DM. Seven days later, diabetic rats were given TRF doses of 30, 60, and 120 mg/kg orally for 21 days. The Morris water maze (MWM) test was performed for memory assessment. Biochemical parameters such as blood glucose, plasma homocysteine (HCY) level, acetylcholinesterase (AChE) activity, reduced glutathione (GSH), superoxide dismutase (SOD) level, and histopathological changes in brain hippocampus and immunohistochemistry for platelet-derived growth factor-C (PDGF-C) expression were evaluated. VaD rats had significantly reduced memory, higher plasma HCY, increased AChE activity, and decreased GSH and SOD levels. However, treatment with TRF significantly attenuated the biochemical parameters and prevented memory loss. Moreover, histopathological changes were attenuated and there was increased PDGF-C expression in the hippocampus of VaD rats treated with TRF, indicating neuroprotective action. In conclusion, this research paves the way for future studies and benefits in understanding the potential effects of TRF in VaD rats.

Epidermal Growth Factor Receptor Kinase Inhibitor Ameliorates ß-Amyloid Oligomer-Induced Alzheimer Disease in Swiss Albino Mice.

Alzheimer's disease (AD) is one of the major neurodegenerative disorders, and its incidence increases globally every year. Currently, available AD drugs symptomatically treat AD with multiple adverse effects. Gefitinib (GE) is an epidermal growth factor receptor (EGFR) kinase inhibitor. EGFR is the preferred target for the treatment of AD, whereas the effect of GE in AD conditions is limited. The present study was designed to explore the ameliorative potential of GE in Aß1-42 oligomer-induced neurotoxicity in AD mice. AD was induced by intracerebroventricular (i.c.v.) injection of Aß1-42 oligomer (4 µg/4 µL) into the lateral ventricles of the mouse brain. The test compound, i.e., GE (2 and 4 mg/kg of body weight), was administered orally on days 10, 13, 16, 19, 22, 25, and 28, and the reference drug, i.e., donepezil (DP, 2 mg/kg), was administered orally from the 10th to 28th days. The behavioral changes were screened by the Morris water maze (MWM) test. Furthermore, biomarkers i.e., brain acetylcholinesterase (AChE), thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) levels were estimated from brain samples. The AD-associated histopathological changes were analyzed by hematoxylin and eosin staining. The administration of GE significantly ameliorated the AD-associated behavioral, biochemical, and histopathological changes. The ameliorative effect of GE against the Aß1-42 oligomer-associated neurotoxicity was due to its potent inhibition of EGFR kinase activation, as well as its antioxidant and antilipid peroxidative effect.

The Attenuating Effect of Beta-Carotene on Streptozotocin Induced Diabetic Vascular Dementia Symptoms in Rats.

This study investigated the ameliorative effects of beta-carotene (BC) on diabetes-associated vascular dementia and its action against biomolecule oxidation. The diabetic vascular dementia (VaD) was induced by administration of nicotinamide (NA; 50 mg/kg; i.p.) and streptozotocin (STZ; 50 mg/kg; i.p.). The test compound, BC (50 and 100 mg/kg; p.o.), and the reference compound, donepezil (DP) (1 mg/kg; p.o.), were administered for 15 consecutive days. Changes in learning and memory were assessed by escape latency time (ELT) and times spent in target quadrant (TSTQ) in the Morris water maze (MWM) test. The changes in neurotransmitter, i.e., acetylcholinesterase (AChE) and oxidative stress markers, i.e., thiobarbituric acid reactive substance (TBARS) and reduced glutathione (GSH), were estimated in hippocampal tissue of the rat brain. The administration of STZ caused significant deterioration of cognitive function (decreased ELT and raised the TSTQ) as compared to the normal group. Treatment with BC and DP diminished the increased AChE activity, TBARS level and decreased GSH level caused by STZ. Thus, BC ameliorates the diabetic vascular complications in VaD due to its potential anticholinergic, antioxidative and free radical scavenging actions.

Physiological and Pathophysiological Role of Cysteine Metabolism in Human Metabolic Syndrome.

Cysteine is one of the major intermediate products of cellular amino-acid metabolism. It is a semi-essential amino acid for protein synthesis. Besides, it is also employed in the regulation of major endogenous anti-oxidant molecule i.e., reduced glutathione (GSH). Further, it is a precursor of multiple sulfur-containing molecules like hydrogen sulfide, lanthionine, taurine, coenzyme A and biotin. It is also one of the key molecules for post-translational modifications of various cellular proteins. In physiological conditions, it is employed in the sulfhydration process and plays a key role in the physiology modification of the inflammatory process in various organs, including the neurological system. The catabolism of cysteine is regulated by cysteine dioxygenase enzyme activity. The dysregulated conditions of cysteine and cysteine-associated hydrogen sulfide metabolism are widely employed in the acceleration of the neurodegenerative process. Moreover, the upregulation of cysteine and hydrogen sulfide synthesis occurs via the reverse trans-sulfuration process. This process helps to manage the worsening of a pathological condition of a cellular system. Moreover, it is also employed in the accumulation of homocysteine contents. Further, both cysteine and homocysteine molecules are widely accepted as biomarkers for various types of diseases. Therefore, the targets involved in the regulation of cysteine have been considered as valid targets to treat various disorders like cardiac disease, ischemic stroke, diabetes, cancer, and renal dysfunction.

Pharmacological evaluation of vanillic acid in rotenone-induced Parkinson's disease rat model.

In the present study, we investigated the anti-Parkinson's effect of vanillic acid (VA) (12 mg/kg, 25 mg/kg, 50 mg/kg p.o.) against rotenone (2 mg/kg s.c.) induced Parkinson's disease (PD) in rats. The continuous administration of rotenone for 35 days resulted in rigidity in muscles, catalepsy, and decrease in locomotor activity, body weight, and rearing behaviour along with the generation of oxidative stress in the brain (rise in the TBARS, and SAG level and reduced CAT, and GSH levels). Co-treatment of VA and levodopa-carbidopa (100 mg/kg + 25 mg/kg p.o.) lead to a significant (P < 0.001) reduction in the muscle rigidity and catalepsy along with a significant (P < 0.001) increase in body weight, rearing behaviour, locomotion and muscle activity as compared to the rotenone-treated group in the dose dependent manner, showing maximum effect at the 50 mg/kg. It also showed reversal of levels of oxidative stress parameters thus, reducing the neuronal oxidative stress. The level of DA was also estimated which showed an increase in the level of DA in the VA plus standard drug treated animals as compared to rotenone treated group. Histopathological evaluation showed a high number of eosinophilic lesions in the rotenone group which were found to be very less in the VA co-treated group. The study thus proved that co-treatment of VA and levodopa-carbidopa, significantly protected the brain from neuronal damage due to oxidative stress and attenuated the motor defects indicating the possible therapeutic potential of VA as a neuroprotective in PD.

Role of ambrisentan (selective endothelin-A receptor antagonist) on cigarette smoke exposure induced cognitive impairment in Danio rerio.

BACKGROUND: Cigarette smoke is exogenous modifiable factors to changes the neurovascular complication. The chronic exposure of cigarette smoke enhances neurocognitive dysfunction. AIMS: The present study is focused on evaluating the role of ambrisentan (selective endothelin-A receptor antagonist) on cigarette smoke-induced cognitive impairment in Danio rerio. MAIN METHODS: The cognitive dysfunction was developed by cigarette smoke exposure (CSE; 10 min in 25 ml of CSE per day) for five days. The selective endothelin-A receptor antagonist i.e., ambrisentan (2.5 to 5 mg/kg; i.p. for five consecutive days) was used for testing of CSE induced cognitive dysfunction. In addition, treatment of reference drug i.e., donepezil (10 mg/kg; i.p. for five consecutive days) was used for this cognitive function study. The cognitive functions were assessed by light and dark chamber; color recognition; partition preference; horizontal compartment; and T-Maze tests. Further, the CSE induced biomarkers changes of the zebrafish brain samples were estimated. KEY FINDINGS: The treatment of ambrisentan showed a potential ameliorative effect against the CSE induced cognitive functions along with attenuation of biochemical changes. The results are comparable to donepezil-treated groups. SIGNIFICANCE: Therefore, ambrisentan can be considered for the attenuation of CSE induced impairment neurocognitive functions due to its reduction of free radical scavenging and neuroinflammatory actions as well as regulation of cholinergic neurotransmitter functions.

Curcumin prevents cigarette smoke extract induced cognitive impairment.

Curcumin is a major phytochemical constituent in Curcuma longa, an herbaceous perennial plant of Zingiberaceae family, which exhibits anti-oxidant, anti-inflammatory and immunomodulatory properties. Here, we studied the therapeutic action of curcumin against CSE induced cognitive impairment in zebrafish. Montelukast (20 mg/kg), a cysteinyl-leukotriene receptor blocker was used as a reference drug. CSE exposure induced biochemical changes revealed that raise the brain acetylcholinesterase activity and lipid peroxidative products; and decrease the reduced glutathione levels in brain samples. Curcumin also protected against CSE induced neurocognitive impairment. These data suggest that curcumin can serve as a phytochemical constituent against CSE induced neurocognitive impairment.

Ischemic-reperfusion of unilateral external iliac artery in rat: A new model for vasculitic femoral neuropathy.

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-α 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.

Therapeutic evaluation of rutin in two-kidney one-clip model of renovascular hypertension in rat.

AIM: The current investigation, designed to investigate the role of rutin in two-kidney one-clip (2K1C) induced renovascular dysfunction associated with hypertension in rat. MAIN METHODS: The renovascular hypertension was developed by the application of vascular clip on left renal artery in rats; the right kidney was kept as such throughout the experimental protocol. The rutin (200 and 300 mg/kg; p.o.) and aliskiren (50mg/kg; p.o.) were administered for 9 consecutive days. The battery of pathophysiological tests i.e., systolic pressure, diastolic pressure and heart rate were performed to assess the anti-hypertensive effect of rutin. In addition, changes of kidney weight/body weight (KW/BW) ratio along with plasma renin content and renal tissue biomarkers i.e., thiobarbituric acid reactive substance (TBAR) and reduced glutathione (GSH) levels were estimated. KEY FINDINGS: The administration of rutin significantly (P<0.05) attenuated the 2K1C of left kidney induced elevated systolic and diastolic pressure in a dose dependent manner. In addition, it also reduces the ratio of KW/BW along with a decrease in plasma renin content, tissue TBARS and increase the GSH levels. There were no significant changes observed in heart rate. Similar results were observed in aliskiren treated group. SIGNIFICANCE: The anti-hypertensive effect of rutin may be a useful herbal medicine for the management of hypertension due to its potential free radical scavenging, inhibition of lipid peroxidation and plasma renin inhibitory action.

Ameliorative potential of vitamin P and digoxin in ischemic-reperfusion induced renal injury using the Langendorff apparatus.

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.

Ameliorative potential of angiotensin-converting enzyme inhibitor (ramipril) on chronic constriction injury of sciatic nerve induced neuropathic pain in mice.

INTRODUCTION: The present study was designed to investigate the effect of ramipril (angiotensin-converting enzyme inhibitor) on the chronic constriction injury of sciatic nerve induced neuropathic pain in mice. METHODS: The neuropathic pain was induced by four loose ligations of the right sciatic nerve in mice. The battery of behavioral tests, i.e. plantar, pin prick, tail flick, tail pinch, rota rod tests, were performed to assess the degree of thermal and mechanical hyperalgesia in ipsilateral paw and tail, and motor in-coordination activity respectively. In addition, the biochemical tests, i.e. total protein, thiobarbituric acid reactive substances and reduced glutathione, were also performed in sciatic nerve tissue samples. RESULTS: The administration of ramipril (2 and 4 mg/kg, p.o.) significantly attenuated chronic constriction injury-induced rise in peripheral as well as central pain sensitivity (thermal and mechanical) along with impairment of motor in-coordination activity. Further, it also produces ameliorative effects on chronic constriction injury-induced rise in thiobarbituric acid reactive substances and decrease in glutathione levels when compared with a normal control group. CONCLUSION: It may be concluded that angiotensin-converting enzyme inhibitor may be a potential new target for the management of neuropathic pain.

Pharmacological evaluation of methanolic leaf extract of Swietenia mahagoni on acrylamide-induced neuropathic pain in rats.

The present study was designed to investigate the antinociceptive effects of methanolic leaf extract of Swietenia mahagoni (MESM) on acrylamide-induced painful neuropathy in rats. The intraperitoneal administration of acrylamide (30 mg/kg; for 24 consecutive days) has been employed for the induction of painful neuropathy. Acrylamide induced nociceptive pain sensitive changes, which have been assessed by hot plate, Von Frey Hair, and tail immersion tests at different time intervals, that is, 0, 6, 12, 18, and 24th day. Furthermore, the biochemical changes, that is, thiobarbituric acid-reactive substances, reduced glutathione, and total calcium levels have been estimated in sciatic nerve tissue on 24th day and histopathological changes have been observed in sciatic nerve tissue sample. MESM and pregabalin have been administered for 14 consecutive days before 1 h of the each acrylamide injection. Administration of acrylamide resulted in significant changes in behavioral and biochemical parameters. Pretreatment of MESM ameliorated acrylamide-induced behavioral, biochemical, and histopathological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. These findings suggested that the neuroprotective effect of S. mahagoni may be due to its potential of antioxidative, calcium channel modulatory, and neuroprotective action.

Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats.

The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

In-vitro evaluation of bioactive compounds, anti-oxidant, lipid peroxidation and lipoxygenase inhibitory potential of Citrus karna L. peel extract.

Many medicinal plants have been studied for their antioxidant and their pharmacological activity. Citrus species were well documented as potential antioxidant based therapy for cancer, inflammation, heart disease. Citrus seeds and peels have been shown to possess high antioxidant activity. Therefore, the present study to explore the antioxidant and lipid peroxidation & lipoxygenase inhibitory action of Citrus karna peel extracts were undertaken. Extraction was performed with different solvents of increasing polarity and yield was calculated. Peel extracts were also analyzed for the presence of phenols, flavonoids, vitamin C, and carotenoids. Then the Citrus karna peel extracts were evaluated for the antioxidant and lipid peroxidation & lipoxygenase inhibitory action In-Vitro. In further, the quantification of hesperidin and naringin was carried out by HPLC-DAD method. The results indicated the presence of phenols, flavonoids, vitamin C, carotenoids, hesperidin and naringin in Citrus karna peel extracts with maximum yield of (3.91% w/w). Citrus karna peel extracts were also found to have potential antioxidant and lipid peroxidation & lipoxygenase inhibitory action. Therefore, Citrus karna peel extracts could be used for the future therapeutic medicine due to presence of potential bioactive compounds.

Drug therapy of neuropathic pain: current developments and future perspectives.

Understanding mechanism of neuropathic pain is too complex and involves both peripheral and central pathophysiological phenomenon. Accordingly the treatment of neuropathic pain is also very complex and is unsatisfactory. The present review attempts to discuss the currently employed pharmacological agents for the management of neuropathic pain including anti-depressants, anti-convulsants, NMDA receptor antagonists, topical & local anesthetics, and upload analgesics. However, the existing pharmacotherapy has marginal efficacy and significant side effects. The review also gives an insight into various pharmacological agents with potential neuropathic pain attenuating properties in experimental models that include NSAIDs, corticosteroids, ion channel blockers (Ca(2+), Na(+), K(+), and TRP channel); ion exchange modulators (NCE and NHE); ion/molecule transport modulators (NKCC-1 and glycine); receptor modulators (kinin, histamine, 5-HT1A, dopamine, alpha & beta adrenergic, purinergic, excitatory amino acid, sigma, ORL1, endothelin, melanocortin, ephrin and PAR); enzyme inhibitors (cytosolic kinase, metalloproteinase, protease, vasopeptidase, D-amino acid oxidase, fatty acid amide hydrolase, aldose reductase and sorbitol dehydrogenase); other ligands (AGE, RAGEs, neuropeptides, neurotrophic factor, complement cascade, cytokine, glial cell & gap junction, nitrous oxide, growth factor, cell adhesion molecule and neuronal sprouting molecule). Moreover, some advanced therapeutic approaches such as neuronal cell transplantation, stem cell therapy, anti-sense oligonucleotide and recombinant therapy have also been dicussed.

Ameliorative effect of Vernonia cinerea in vincristine-induced painful neuropathy in rats.

The present study was designed to investigate the antinociceptive potential of Vernonia cinerea (VC) on vincristine-induced painful neuropathy in rats. A chemotherapeutic agent, vincristine (50 µg/kg intraperitoneally for 10 consecutive days), was administered for the induction of neuropathic pain in rats. The painful behavioral changes were assessed using hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests to assess the degree of hyperalgesic and allodynic pain sensation in paw and tail. Tissue biomarker changes including thiobarbituric acid reactive substances (TBARSs), reduced glutathione (GSH) and total calcium levels were estimated in sciatic nerve tissue samples to assess the degree of oxidative stress. Histopathological changes were also observed in transverse sections of rat sciatic nerve tissue. Ethanolic extract of VC leaves and pregabalin were administered for 14 consecutive days from day 0 (day of surgery). Pregabalin served as a positive control in the present study. Vincristine administration resulted in a significant reduction in painful behavioral changes along with a rise in the levels of TBARS, total calcium and decrease in GSH levels when compared with the normal control group. Furthermore, significant histopathological changes were also observed. Pretreatment with VC significantly attenuated vincristine-induced development of painful behavioral, biochemical and histological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. The attenuating effect of VC in vincristine-induced nociceptive painful sensation may be due to its potential of antioxidative, neuroprotective and calcium channel inhibitory action.

Antinociceptive effect of Butea monosperma on vincristine-induced neuropathic pain model in rats.

Neuropathic pain is a chronic neurodegenerative disease. It is well characterized by spontaneous pain, hyperalgesia, hypothesia, dysesthesia and allodynia. The present study was designed to investigate the antinociceptive potential of Butea monosperma on vincristine-induced painful neuropathy in rats. Vincristine was administered for induction of neuropathic pain in experimental animals. Hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal hyperalgesia, cold chemical allodynia, mechanical hyperalgesia and allodynia in the hind paw and tail thermal hyperalgesia, respectively, as an index of peripheral and central pain sensation. Tissue thiobarbituric acid reactive substances (TBARSs), reduced glutathione (GSH) and total calcium levels were estimated to assess the biochemical changes in the sciatic nerve tissue. Microscopically, histopathological changes were also observed in the sciatic nerve tissue. Ethanolic extract of B. monosperma leaves and pregabalin were administered for 14 consecutive days. Vincristine administration resulted in significant reduction in behavioural (i.e. hyperalgesia and allodynic pain sensation) changes along with a rise in the levels of TBARS, total calcium and decrease in GSH levels when compared with the normal control group. Moreover, significant histological changes were also observed. Pretreatment with B. monosperma significantly attenuated vincristine-induced development of painful behavioural, biochemical and histological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. B. monosperma ameliorated vincristine-induced painful neuropathy. It may be due to its potential of antioxidative, neuroprotective and calcium channel inactivation.

Neuroprotective effect of gadolinium: a stretch-activated calcium channel blocker in mouse model of ischemia-reperfusion injury.

The present study was designed to investigate the potential of gadolinium, a stretch-activated calcium channel blocker in ischemic reperfusion (I/R)-induced brain injury in mice. Bilateral carotid artery occlusion of 12 min followed by reperfusion for 24 h was given to induce cerebral injury in male Swiss mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using Morris water maze test and motor incoordination was evaluated using rota-rod, lateral push, and inclined beam walking tests. In addition, total calcium, thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), and acetylcholinesterase (AChE) activity were also estimated in brain tissue. I/R injury produced a significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Furthermore, I/R injury also produced a significant increase in levels of TBARS, total calcium, AChE activity, and a decrease in GSH levels. Pretreatment of gadolinium significantly attenuated I/R-induced infarct size, behavioral and biochemical changes. On the basis of the present findings, we can suggest that opening of stretch-activated calcium channel may play a critical role in ischemic reperfusion-induced brain injury and that gadolinium has neuroprotective potential in I/R-induced injury.