PubMed Health⌕ Search

Biomedical subjects

P S Naidu

Publications and source records attributed to P S Naidu.

At least 19 recordsLinked to original sources
PubMed2006

Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats.

Alzheimer's disease is a complex and multifactorial neurodegenerative disease. Central administration of colchicine, a microtubule-disrupting agent, causes loss of cholinergic neurons and cognitive dysfunction that is associated with excessive free radical generation. The present study was aimed at evaluating the effects of trans-resveratrol in the prevention of colchicine-induced cognitive impairment and oxidative stress in rats. Intracerebroventricular administration of colchicine (15 microg/5 microl) induced impaired cognitive functions in both the Morris water maze task and the elevated plus-maze task. Chronic treatment with resveratrol (10 and 20 mg/kg, p.o.) for a period of 25 days, beginning 4 days prior to colchicine injection, significantly improved the colchicine-induced cognitive impairment. Intracerebroventricular colchicine injection resulted in free radical generation characterized by alterations in oxidative stress markers with a significant increase in malondialdehyde (MDA) and nitrite levels and depletion of reduced glutathione (GSH) activity in the rat brains. It also showed a significant decrease in acetylcholinesterase activity. Besides improving cognitive dysfunction, chronic administration of resveratrol significantly reduced the elevated MDA and nitrite levels and restored the depleted GSH and acetylcholinesterase activity. Results of the present study indicated that trans-resveratrol has a neuroprotective role against colchicine-induced cognitive impairment and associated oxidative stress.

Acetylcholinesterase↗
PubMed2006

Involvement of peripheral prostaglandins in formalin-induced nociceptive behaviours in the orofacial area of rats.

Prostaglandins (PGs) are known to be involved in the pathogenesis of inflammation and pain. However, their role in orofacial pain is not clearly understood. The present study was undertaken to determine the effect of systemic and locally administered nonsteroidal anti-inflammatory drugs (NSAIDs) on the role of PGs in orofacial pain induced by formalin in rats. The subcutaneous injection of formalin into the rat upper lip generated behavioural responses that lasted for several minutes. The orofacial responses due to formalin were seen in two distinct phases, the early response (0-3 min) and the continuous prolonged response (9-45 min). Systemic administration of ketorolac or diclofenac (10 and 30 mg/kg, i.p.) significantly attenuated formalin-induced nociceptive behaviour in the phase-2, but not in the phase-1 of the formalin test. Similarly, subcutaneous (local) administration of ketorolac or diclofenac in the orofacial area (100 and 300 microg/lip) markedly decreased the phase-2 nociceptive response due to formalin. However, both the drugs had no effect on the phase-1 response of the formalin test. These results suggest that PGs, particularly peripheral PGs are involved in nociceptive behaviour following formalin injection in the orofacial area.

Animals↗
PubMed2005

Protective effect of quercetin on alcohol abstinence-induced anxiety and convulsions.

Chronic administration of ethanol (2 g/kg, p.o.) on days 1-6 and its withdrawal produced an anxiogenic reaction in mice as assessed in the mirrored-chamber test. Daily administration of quercetin (25 or 50 mg/kg, p.o.) prior to ethanol for 6 days prevented withdrawal-induced anxiety in mice. However, acute administration of a single dose of quercetin (50 mg/kg) to animals withdrawn from ethanol, i.e., on day 7, did not prevent withdrawal-induced anxiety. Ethanol withdrawal also induced a significant increase in the locomotor activity of mice indicating an anxiogenic response. Daily administration of quercetin (25 or 50 mg/kg, p.o.) prior to ethanol for 6 days prevented withdrawal-induced increased locomotor activity. Ethanol withdrawal also sensitized the convulsogenic reaction to pentylenetetrazole (PTZ). A non-convulsive dose (40-60 mg/kg) of PTZ produced full-blown convulsions and increased mortality in ethanol-withdrawn mice. Both acute and chronic administration of quercetin (25 or 50 mg/kg, p.o.) produced a significant protection against ethanol withdrawal-induced reduction in PTZ threshold in mice. The result suggests the protective effect of this safe drug, quercetin, in the management of ethanol withdrawal reactions.

Alcohol Withdrawal Seizures↗
PubMed2004

Quercetin, a bioflavonoid, reverses haloperidol-induced catalepsy.

Neuroleptics are extensively used in the treatment of schizophrenia and other affective disorders. Unfortunately their use is often associated with distressing side effects involving the extrapyramidal tract, such as Parkinsonism and tardive dyskinesia. Neuroleptic-induced catalepsy has long been used as a model for extrapyramidal side effects such as Parkinsonian-like bradykinesia associated with antipsychotic use in humans. In the present study, haloperidol (2 mg/kg i.p.) was administered to mice to induce catalepsy and cataleptic response was measured for the next 4 h at 1 h intervals. Haloperidol treatment in mice induced a strong cataleptic state within 1 h of injection, reaching a maximal plateau after 2 h and lasting for 4 h. Vehicle-treated animals did not display catalepsy as they remained less than 5 sec on the bar at each time point. Pretreatment with quercetin dose-dependently (25-100 mg/kg p.o.) reduced the catalepsy score in haloperidol-treated animals. A dose response study of quercetin showed a characteristic U-shaped response curve, with maximum suppression observed at a dose of 100 mg/kg. On increasing the dose of quercetin to 300 mg/kg, no statistically significant difference in catalepsy score was observed compared with the haloperidol-treated group. In conclusion, the findings of the present study strongly suggest that quercetin can be screened as a potential drug candidate or as an adjuvant for the treatment of neuroleptic-induced extrapyramidal side effects.

Animals↗
PubMed2004

Protective effect of bupropion on morphine tolerance and dependence in mice.

Possible reversal of morphine-induced tolerance and dependence by bupropion was studied in mice. A 10-day repeated injection regimen was followed to induce morphine tolerance and dependence. Bupropion (2 and 5 mg/kg) per se, when chronically administered for 9 days, failed to produce any significant change in tail-flick latency compared with the control mice. Chronic administration of bupropion (2 or 5 mg/kg) during the induction phase (days 1-9) delayed the development of tolerance to the antinociceptive action of morphine and also reversed naloxone- (2 mg/kg) precipitated withdrawal jumps. On the other hand, acute administration of bupropion (2 or 5 mg/kg) on day 10, i.e., during the expression phase of morphine dependence, reduced the incidence of naloxone-precipitated withdrawal jumps without affecting tolerance to the analgesic effect. In conclusion, results of the present study suggest the potential use of bupropion in tolerance and dependence.

Analgesics, Opioid↗
PubMed2001

Possible involvement of prostaglandins in haloperidol-induced orofacial dyskinesia in rats.

Dopaminergic abnormality is one of the pathological mechanisms involved in the pathophysiology of tardive dyskinesia, a late complication of neuroleptic treatment. Prostaglandins modulate the dopamine release in the striatum, the principle area involved in the pathophysiology of tardive dyskinesia. Rats were chronically treated with haloperidol (HPD) (1.5 mg/kg) for a period of 21 days, to induce orofacial dyskinesia. Behavioural assessment of orofacial dyskinesia was done 24 h after the last dose of haloperidol. Catalepsy was induced in rats by acute treatment with haloperidol (1 mg/kg), and catalepsy was scored for the next 4 h. Chronic haloperidol treatment induced profound vacuous chewing movements in rats. Indomethacin, a nonselective cyclooxygenase inhibitor dose-dependently (5-20 mg/kg) suppressed the vacuous chewing movements count in haloperidol-treated animals. In conclusion, the results of the present study infer that prostaglandins might play a significant role in the haloperidol-induced vacuous chewing movements, and prostaglandin synthesis inhibitors can serve as novel drug candidates for the treatment of tardive dyskinesia.

Animals↗
PubMed2001

Effect of 5-HT1A and 5-HT2A/2C receptor modulation on neuroleptic-induced vacuous chewing movements.

Tardive dyskinesia is a serious motor side effect of chronic neuroleptic therapy. Chronic treatment or rats with neuroleptics leads to the development of abnormal oral movements called vacuous chewing movements. Vacuous chewing movements in rats are widely accepted as an animal model of tardive dyskinesia. Atypical antipsychotics such as clozapine and rispiridone are associated with a lower incidence of extrapyramidal side effects and tardive dyskinesia. The present study was aimed to explore the role of 5-HT1A, 5-HT2A/2C receptors in the expression of neuroleptic-induced orofacial dyskinesia. In the present study rats were chronically (for 21 days) treated with haloperidol (1.5 mg/kg, i.p.) to elicit vacuous chewing movements. The neuroleptic-induced vacuous chewing movements, viz., vertical jaw movements, tongue protrusions and bursts of jaw tremors, were counted during a 5-min observation period. Acute treatment with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, dose-dependently (0.05, 0.1 and 0.2 mg/kg, i.p.) reduced the haloperidol-induced vacuous chewing movements and headshakes. Both acute and chronic administration of seganserin, ketanserin and ritanserin, 5-HT2A/2C receptor antagonists, also reduced haloperidol-induced vacuous chewing movements in a dose-dependent (0.05, 0.1 and 0.2 mg/kg, i.p.) manner. In acute studies a higher dose of ritanserin (1 mg/kg) but not ketanserin (1 mg/kg) increased vacuous chewing movements, whereas a higher dose of seganserin (1 mg/kg) did not have any effect on vacuous chewing movements. All the drugs reduced haloperidol-induced headshakes in a dose-dependent fashion. These findings indicate that the serotonergic system, and particularly 5-HT1A and 5-HT2A/2C receptors, may be involved in haloperidol-induced orofacial dyskinesia, and that 5-HT receptors may provide novel targets for the development of drugs that can be used to reverse or prevent the extrapyramidal side effects associated with long-term antipsychotic treatment.

Animals↗
PubMed2001

Reversal of reserpine-induced vacuous chewing movements in rats by melatonin: involvement of peripheral benzodiazepine receptors.

Several reports have indicated that melatonin modulates striatal dopaminergic functions via its interaction with central and peripheral benzodiazepine (BZ) receptors. Clinical reports and animal studies speculated on the possible involvement of melatonin in the pathophysiology of tardive dyskinesia (TD). In view of this, the present experiment was performed to study the possible effect of melatonin in modulation of reserpine-induced dyskinesia. Melatonin (1-10 mg/kg) dose dependently suppressed the severity of vacuous chewing movements (VCMs) in rats. Prior administration of the putative melatonin receptor antagonists luzindole (2.5 and 5 mg/kg) or prazosin (2.5 and 5 mg/kg) failed to antagonize melatonin (2.5 mg/kg) reversal of reserpine-induced VCMs. However, the peripheral BZ receptor antagonist PK11195 (0.5 and 1 mg/kg) but not flumazenil (1 and 2 mg/kg), dose dependently antagonized melatonin's reversal of reserpine-induced VCMs. Taken together the present results demonstrate that melatonin reverses reserpine-induced VCMs and that this could be due to enhancement of GABAergic activity via peripheral BZ receptors.

Adrenergic Uptake Inhibitors↗
PubMed2001

Reversal of neuroleptic-induced orofacial dyskinesia by 5-HT3 receptor antagonists.

Tardive dyskinesia, a syndrome of abnormal, involuntary hyperkinetic movements that occurs during long-term neuroleptic therapy is a major limitation of chronic neuroleptic therapy. The pathophysiology of tardive dyskinesia is still an enigma. The objective of the present study was to elucidate the role of 5-HT3 receptor involvement in neuroleptic-induced vacuous chewing movements in rats. Rats chronically (for 21 days) treated with haloperidol (1.5 mg/kg, i.p.) significantly developed vacuous chewing movements, as compared to vehicle-treated controls. Both ondansetron and tropisetron dose-dependently (0.25, 0.5 and 1.0 mg/kg, i.p.) reversed the haloperidol-induced vacuous chewing movements. Serotonin acting through 5-HT3 receptors might play a significant role in the pathophysiology of tardive dyskinesia, and 5-HT3 receptor ligands can be exploited as novel therapeutic agents for the treatment of tardive dyskinesia.

Animals↗
PubMed2001

Excitatory mechanisms in neuroleptic-induced vacuous chewing movements (VCMs): possible involvement of calcium and nitric oxide.

Tardive dyskinesia (TD) is a serious motor side-effect of chronic neuroleptic therapy. Chronic treatment with neuroleptics leads to the development of oral abnormal movements in rats known as vacuous chewing movements (VCMs). Vacuous chewing movements in rats have been widely accepted as an animal model of tardive dyskinesia. Chronic blockade of D2 inhibitory dopamine (DA) receptors localized on glutamatergic terminals in the striatum leads to the persistent enhanced release of glutamate that kills the striatal output neurons. The object of the present study was to explore the role of glutamatergic modulation on the neuroleptic-induced VCMs. Rats were chronically (for 21 days) treated with haloperidol (1.5 mg/kg, i.p.) to produce VCMs. The neuroleptic-induced VCMs viz., vertical jaw movements, tongue protrusions and bursts of jaw tremors, were counted during a 5 min observation period. Dizocilpine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, dose dependently (0.02 and 0.05 mg/kg) reduced haloperidol-induced VCMs. Felodipine (5 and 10 mg/kg), an L-type calcium-channel blocker, also significantly reduced the VCM count. N-omega-nitro-L-arginine methyl ester (L-NAME) (25 and 50 mg/kg), a nitric oxide synthase inhibitor, also reduced the VCM count in an L-arginine-sensitive manner. In conclusion, the findings of the present study indicated NMDA receptor involvement in haloperidol-induced VCMs, and also suggested the possible involvement of calcium and nitric oxide in haloperidol-induced VCMs.

Animals↗
PubMed2001

Animal models of tardive dyskinesia--a review.

Tardive dyskinesia is a serious motor side effect of long term neuroleptic therapy, with an unknown pathophysiological basis. The leading hypothesis of the pathophysiology of tardive dyskinesia includes dopamine receptor supersensitivity, GABAergic hypofunction, excitotoxicity and oxidative stress. Many preclinical models have been developed to identify the underlying pathological processes of tardive dyskinesia, but none has yet produced a parsimonious results. A wide range of animal models, viz. Homologous, analogous and correlational models have been developed to explore the pathophysiology of tardive dyskinesia. Vacuous chewing movements in rodents induced by chronic neuroleptic treatment is the most frequently employed model. As the existing models suffer from several phenomenological and methodological problems, development of new models, highly predictive of pathological basis of tardive dyskinesia can accelerate tardive dyskinesia research for the better understanding of the pathophysiological processes underlying the syndrome and for the discovery of new therapeutic targets for the treatment of tardive dyskinesia.

Animals↗
PubMed2000

Differential role of dopamine D1 and D2 receptors in isoniazid-induced vacuous chewing movements.

Tardive dyskinesia (TD) is a syndrome of potentially irreversible and involuntary hyperkinetic disorders that occurs during chronic neuroleptic therapy and is a major limitation of such therapy. Vacuous chewing movements (VCMs) in rats have been widely accepted as an animal model of tardive dyskinesia. In the present study isoniazid (1, 2 and 5 microM i.c.v.) dose-dependently produced VCMs in rats. The response produced by a 10-microM dose was lower than that of earlier doses but was statistically significant when compared to a saline-treated group. Diazepam (1 and 4 mg/kg i.p.) and progabide (50 and 100 mg/kg i.p.) dose-dependently reversed the isoniazid-induced VCMs. Haloperidol (0.5 and 1 mg/kg i.p.) and SCH-23390 (0.25 and 0.5 mg/kg i.p.) reversed the isoniazid-induced VCMs in a dose-dependent manner. Sulpiride (25 and 50 mg/kg i.p.), a dopamine D2 receptor antagonist, had no effect on isoniazid-induced VCMs. SKF-38393 (10 and 15 mg/kg i.p.) dose-dependently augmented the isoniazid-induced VCMs. Quinpirole 0.02 mg/kg i.p. had no effect on isoniazid-induced VCMs but a higher quinpirole dose (0.05 mg/kg) significantly reduced isoniazid-induced VCMs. Isoniazid (2 microM i.c.v.) produced stereotypy (grooming and rearing) in rats. Haloperidol (0.5 and 1 mg/kg i.p.), SCH-23390 (0.25 and 0.5 mg/kg i.p.) and sulpiride (25 and 50 mg/kg i.p.) decreased the severity of isoniazid-induced stereotypy. SKF-38393 (10 and 15 mg/kg i.p.) dose-dependently augmented the isoniazid-induced grooming behavior more prominently as compared to quinpirole (0.02 and 0.05 mg/kg i.p.); on the other hand quinpirole potentiated isoniazid-induced rearing behavior. In conclusion, the results of the present study demonstrated the differential involvement of dopamine D1 and D2 receptors in isoniazid-induced VCMs.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

Calcium-calmodulin mediates bradykinin-induced MAPK phosphorylation and c-fos induction in vascular cells.

The vasoactive peptide bradykinin (BK) has been implicated in the pathophysiology of a number of vascular wall abnormalities, but the cellular mechanisms by which BK generates second messengers that alter vascular function are as yet undefined. Exposure of vascular smooth muscle cells (VSMC) to BK (10(-7) M) produced a rapid and transient rise in intracellular calcium, which preceded an increase in tyrosine phosphorylation of mitogen-activated protein kinase (MAPK). MAPK activation by BK was observed as early as 1 min, peaked at 5 min, and returned to baseline by 20 min. Treatment of cells with the intracellular calcium chelator EGTA-acetoxymethyl ester inhibited BK-stimulated MAPK activation, suggesting that intracellular calcium mobilization contributes to the activation of MAPK. The calmodulin inhibitor W-7 also markedly inhibited BK-induced MAPK phosphorylation in the cytoplasm as well as in the nucleus. Moreover, the BK-induced increase in c-fos mRNA levels was significantly inhibited by the calmodulin inhibitor, indicating that calmodulin is required for BK signaling leading to c-fos induction. These results implicate the calcium-calmodulin pathway in the mechanisms for regulating MAPK activity and the resultant c-fos expression induced by BK in VSMC.

Animals↗
PubMed1997

Bradykinin induces tubulin phosphorylation and nuclear translocation of MAP kinase in mesangial cells.

Glomerular hypertension and glomerular hypertrophy act early and synergistically to promote glomerular injury in diabetes. We have previously shown that increased renal kinin production contributes to the glomerular hemodynamic abnormalities associated with diabetes. Glomerulosclerosis, characterized by mesangial cell proliferation and matrix expansion, is the final pathway leading to renal failure. The signal(s) initiating mesangial cell proliferation is ill defined. In the present study, we utilized immunofluorescence, immunoprecipitation, and immunoblotting techniques to identify substrates that are tyrosine phosphorylated in response to bradykinin action in mesangial cells. Immunofluorescence microscopy of mesangial cells stained with anti-phosphotyrosine (anti-PY) antibodies following bradykinin treatment (10(-9)-10(-6) M) revealed a dose-dependent increase in the labeling of cytoplasmic and nuclear proteins. Immunoprecipitation with anti-PY, followed by immunoblot revealed bradykinin-induced tyrosyl phosphorylation of tubulin and mitogen-activated protein kinase (MAPK). Confocal microscopy of mesangial cells stained for MAPK indicated that bradykinin stimulation resulted in translocation of MAPK from the cytoplasm to the nucleus by 2 h. These data demonstrate that bradykinin action results in the tyrosine phosphorylation of cellular proteins in mesangial cells and suggest a role for tubulin and MAPK in the signaling cascade of bradykinin leading to altered mesangial function.

Animals↗
PubMed1995

Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.

The basic helix-loop-helix muscle regulatory factor (MRF) gene family encodes four distinct muscle-specific transcription factors known as MyoD, myogenin, Myf-5, and MRF4. These proteins represent key regulatory factors that control many aspects of skeletal myogenesis. Although the MRFs often exhibit overlapping functional activities, their distinct expression patterns during embryogenesis suggest that each protein plays a unique role in controlling aspects of muscle development. As a first step in determining how MRF4 gene expression is developmentally regulated, we examined the ability of the MRF4 gene to be expressed in a muscle-specific fashion in vitro. Our studies show that the proximal MRF4 promoter contains sufficient information to direct muscle-specific expression. Located within the proximal promoter are a single MEF2 site and E box that are required for maximum MRF4 expression. Mutation of the MEF2 site or E box severely impairs the ability of this promoter to produce a muscle-specific response. In addition, the MEF2 site and E box function in concert to synergistically activate the MRF4 gene in nonmuscle cells coexpressing MEF2 and myogenin proteins. Thus, the MRF4 promoter is regulated by the MEF2 and basic helix-loop-helix MRF protein family through a cross-regulatory circuitry. Surprisingly, the MRF4 promoter itself is not transactivated by MRF4, suggesting that this MRF gene is not subject to an autoregulatory pathway as previously implied by other studies. Understanding the molecular mechanisms regulating expression of each MRF gene is central to fully understanding how these factors control developmental events.

Animals↗
PubMed1993

Temporal expression of the major lignin peroxidase genes of Phanerochaete chrysosporium.

DNA probes specific for the genes encoding major lignin peroxidase (LIP) isozymes H2, H8, and H10 of Phanerochaete chrysosporium were constructed. These probes were used to study the temporal expression of the three lip genes in defined low-nitrogen medium. H2 gene transcripts were produced at high levels on days 4, 5, and 7 and at low levels on day 6, while the H8 gene transcripts peaked on day 4 and were produced in substantially lower amounts thereafter. H10 transcripts, on the other hand, peaked on day 4, dropped precipitously on day 5, and were barely detectable on days 6 and 7. There was no precise correlation between lip transcript and isozyme levels.

Base Sequence↗
PubMed1990

Characterization of a new lignin peroxidase gene (GLG6) from Phanerochaete chrysosporium.

Sequence analysis of a new lignin peroxidase (LIP) gene, GLG6, from P. chrysosporium showed that it encodes a mature LIP protein with a predicted Mr of 36,454. A 28 aa signal peptide precedes the mature protein. The coding region of GLG6 is interrupted by nine introns ranging in size from 50-57 bp. GLG6 encoded-LIP has 72%, 88% and 82% homology, respectively, to the LIP isozymes H2, H3, and H10. Comparison of the N-terminal sequence of GLG6-encoded LIP to that of the LIP proteins H2, H8, H10 also showed that the former is relatively less related to the H2 protein than it is to the H8 and H10 proteins. Expression of GLG6, similar to the other LIP genes, occurs only during secondary metabolism.

Amino Acid Sequence↗