Antioxidant activity of active tannoid principles of Emblica officinalis (amla).

The antioxidant activity of tannoid active principles of E. officinalis consisting of emblicanin A (37%), emblicanin B (33%), punigluconin (12%) and pedunculagin (14%), was investigated on the basis of their effects on rat brain frontal cortical and striatal concentrations of the oxidative free radical scavenging enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), and lipid peroxidation, in terms of thiobarbituric acid-reactive products. The results were compared with effects induced by deprenyl, a selective monoamine oxidase (MAO) B inhibitor with well documented antioxidant activity. The active tannoids of E. officinalis (EOT), administered in the doses of 5 and 10 mg/kg, i.p., and deprenyl (2 mg/kg, i.p.), induced an increase in both frontal cortical and striatal SOD, CAT and GPX activity, with concomitant decrease in lipid peroxidation in these brain areas when administered once daily for 7 days. Acute single administration of EOT and deprenyl had insignificant effects. The results also indicate that the antioxidant activity of E. officinalis may reside in the tannoids of the fruits of the plant, which have vitamin C-like properties, rather than vitamin C itself.     

Effect of bioactive tannoid principles of Emblica officinalis on iron-induced hepatic toxicity in rats.

The tannoid principles of the fruits of the plant Emblica officinalis Gaertn comprising of emblicanin A. emblicanin B, punigluconin and pedunculagin, have been reported to exhibit antioxidant activity in vitro and in vivo. In the present study, an emblicanin A (37%) and B (33%) enriched fraction of fresh juice of Emblica fruits (EOT), administered prophylactically (10, 20 and 50 mg/kg, p.o.) for 10 consecutive day, was found to inhibit acute iron overload (30 mg/kg, i.p.) hepatic lipid peroxidation and the increase of serum levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, used as markers of the induced hepatic dysfunction. A similar effect was produced by silymarin (20 mg/kg, p.o.), an antioxidant hepatoprotective agent. The results support the use of Emblica fruits for hepatoprotection in Ayurveda.     

Effect of Withania somnifera glycowithanolides on a rat model of tardive dyskinesia.

Withania somnifera glycowithanolides (WSG) were investigated for their preventive effect on the animal model of tardive dyskinesia (TD), induced by once daily administration of the neuroleptic, haloperidol (1.5 mg/kg, i.p.), for 28 days. Involuntary orofacial movements (chewing movements, tongue protusion and buccal tremors) were assessed as TD parameters. WSG (100 and 200 mg, p.o.), administered concomitantly with haloperidol for 28 days, inhibited the induction of the neuroleptic TD. Haloperidol-induced TD was also attenuated by the antioxidant, vitamin E (400 and 800 mg/kg, p.o.), but remained unaffected by the GABA-mimetic antiepileptic agent, sodium valproate (200 and 400 mg/kg, p.o.), both agents being administered for 28 days like WSG. The results indicate that the reported antioxidant effect of WSG, rather than its GABA-mimetic action, may be responsible for the prevention of haloperidol-induced TD.     

Effect of bioactive tannoid principles of Emblica officinalis on ischemia-reperfusion-induced oxidative stress in rat heart.

The tannoid principles of the fruits of Emblica officinalis have been reported to exhibit antioxidant activity in vitro and in vivo. In the present study, an emblicanin-A (37%) and -B (33%) enriched fraction of fresh juice of Emblica fruits (EOT) was investigated for antioxidant activity against ischemia-reperfusion (IRI)-induced oxidative stress in rat heart. Vitamin E (VE) was used as the standard antioxidant agent. IRI was induced in isolated rat heart by perfusing it with modified Kreb-Hensleitt's solution for 5 min, followed by a period of ischemia (stoppage of perfusion) for 10 min and then restoring the perfusion (reperfusion) for 15 min. IRI induced a significant decrease in the activities of cardiac superoxide dismutase, catalase and glutathione peroxidase, with a concomitant increase in lipid peroxidation. These IRI-induced effects were prevented by the administration of EOT (50 and 100 mg/kg body wt.) and VE (200 mg/kg body wt.) given orally twice daily for 14 days prior to the sacrifice of the animals and initiation of the perfusion experiments. The study confirms the antioxidant effect of E. officinalis and indicates that the fruits of the plant may have a cardioprotective effect.     

Antioxidant activity of tannoid principles of Emblica officinalis (amla) in chronic stress induced changes in rat brain

Effect of tannoid principles emblicanin A, emblicanin B, punigluconin, and pedunculagin of E. officinalis was assessed on chronic unpredictable footshock-induced stress-induced perturbations in oxidative free radical scavanging enzymes in rat brain frontal cortex and striatum. Chronic stress, administered over a period of 21 days, induced significant increase in rat brain frontal cortical and striatal superoxide dismutase (SOD) activity, concomitant with significant reduction in catalase (CAT) and glutathione peroxidase (GPX) activity. The changes in the enzyme activities was accompanied by an increase in lipid peroxidation, in terms of augmented thiobarbituric acid-reactive products. Administration of Emblica tannoids (10 and 20 mg, po) for 21 days, concomitant with the stress procedure, induced a dose-related alteration in the stress effects. Thus, a tendency towards normalization of the activities of SOD, CAT and GPX was noted in both the brain areas, together, with reduction in lipid peroxidation. The results indicate that the reported antistress rasayana activity of E. officinalis may be, at least partly due to its tendency to normalize stress-induced perturbations in oxidative free radical scavenging activity, in view of the postulate that several stress-induced diseases, including the process of aging, may be related to accumulation of oxidative free radicals in different tissues.     

Antioxidant effects of Emblica officinalis and Zingiber officinalis on arsenic and lead induced toxicity on Albino rats

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/ kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats. Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.     

Garlic and vitamin E provides antioxidant defence in tissues of female rats treated with nicotine

Nicotine is known to induce oxidative stress in rat tissues and the antioxidant properties of garlic have been reported. This study was designed to determine if the peroxidative damage caused by nicotine administration can be effectively prevented with garlic juice, and vitamin E, a known antioxidant.Four groups of six rats each were divided into: Group I: (control) received 0.2ml of 0.9% normal saline, group II (received nicotine 0.6mg/kg b.w subcutaneously), group III (received nicotine 0.6mg/kg b.w + garlic juice 100mg/kg b.w orally), and group IV (received nicotine 0.6mg/kg b.w + Vitamin E 100mg/kg b.w orally). All animals were treated for 21 days. The pituitary gland, ovary, uterus, heart, liver and kidney of the animals were harvested, weighed and homogenized. Malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were then measured.Concentration of MDA was significantly increased in tissues of nicotine treated rats when compared with the control. In group III and IV, MDA levels were significantly reduced when compared with nicotine group. The activities of SOD and GSH significantly decreased in group II (nicotine only) rat tissues, while it was significantly increased in group III and IV rat tissues. The study showed that garlic juice extract (100mg/kg b.w) and vitamin E (100mg/kg b.w) administration prevented oxidative damage in rat tissues treated with nicotine. The study also showed that vitamin E has a more potent antioxidant activity than garlic juice in preventing nicotine induced oxidative damage in rat. Keywords: Nicotine, Vitamin E, Garlic, antioxidant.     

Protective Effect of L-type Calcium Channel Blockers Against Haloperidol-induced Orofacial Dyskinesia: A Behavioural, Biochemical and Neurochemical Study

Haloperidol is a classical neuroleptic drug that is still in use and can lead to abnormal motor activity such as tardive dyskinesia (TD) following repeated administration. TD has no effective therapy yet. There is involvement of calcium in triggering the oxidative damage and excitotoxicity, both of which play central role in haloperidol-induced orofacial dyskinesia and associated alterations. The present study was carried out to investigate the protective effect of calcium channel blockers [verapamil (10 and 20 mg/kg), diltiazem (10 and 20 mg/kg), nifedipine (10 and 20 mg/kg) and nimodipine (10 and 20 mg/kg)] against haloperidol induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical alterations in rats. Chronic administration of haloperidol (1 mg/kg i.p., 21 days) resulted in a significant increase in orofacial dyskinetic movements and significant decrease in % retention, coupled with the marked increase in lipid peroxidation and superoxide anion generation where as significant decrease in non protein thiols and endogenous antioxidant enzyme (SOD and catalase) levels in rat brain striatum homogenates. All these deleterious effects of haloperidol were significantly attenuated by co-administration of different calcium channel blockers. Neurochemically, chronic administration of haloperidol resulted in significant decrease in levels of catecholamines (dopamine, serotonin) and their metabolites (HVA and HIAA) but increased turnover of dopamine and serotonin. Co-administration of most effective doses of verapamil, diltiazem, nifedipine and nimodipine significantly attenuated these neurochemical changes. Results of the present study indicate that haloperidol-induced calcium ion influx is involved in the pathogenesis of tardive dyskinesia and calcium channel blockers should be tested in clinical trials with nifedipine as the most promising one.     

Antioxidants and antioxidant enzymes protect against pulmonary oxygen toxicity in the rabbit

Two major lines of defense exist against oxidant lung injury: tissue antioxidants and antioxidant enzymes. We studied pretreatment with the antioxidants, vitamin E and butylated hydroxyanisole (BHA), and the antioxidant enzymes, superoxide dismutase (SOD) and catalase, in rabbits exposed to 100% O2 for 48 h. BHA (200 mg/kg ip) or vitamin E (50-100 mg/kg po) were given for 2 or 3 days, respectively, before O2 exposure. Combined therapy with polyethylene glycol- (PEG) conjugated SOD (12 mg/kg) and catalase (200,000 U/kg) was given intraperitoneally 1 h before and 24 h after beginning 100% O2. Hyperoxia significantly increased the pulmonary content of malondialdehyde, indicating enhanced lipid peroxidation. One hundred percent O2 also increased lung weight gain and alveolar-capillary permeability to aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA, 500 mol wt) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt). Pretreatment with vitamin E, BHA, or the combination of PEG-SOD and PEG-catalase prevented the increase in malondialdehyde, lung weight gain, and alveolar-capillary permeability caused by hyperoxia. These results indicate that augmenting either tissue antioxidants or antioxidant enzymes can prevent the pulmonary injury caused by 48 h of 100% O2 in rabbits.     

Molecular and biochemical investigations on the effect of quercetin on oxidative stress induced by cisplatin in rat kidney

The present study was aimed to investigate the ability of quercetin (QE) to ameliorate adverse effects of cisplatin (Cis.) on the renal tissue antioxidants by investigating the kidney antioxidant gene expression and the antioxidant enzymes activity. Forty rats divided into. Control rats. QE treated rats were orally administered 100 mg QE/kg for successive 30 days. Cis. injected rats were administered i.p. Cis. (12 mg/kg b.w.) for 5 mutual days. Cis. + QE rats were administered Cis. i.p. (12 mg/kg) and orally administered 100 mg QE/kg for consecutive 30 days. The obtained results indicated that Cis. induced oxidative stress in the renal tissue. That was through induction of free radical production, inhibition of the activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) as well their genes expression. At the same time, vitamin E, vitamin C and reduced glutathione (GSH) levels were decreased. QE had the ability to overcome cisplatin-induced oxidative stress through the reduction of free radical levels. The antioxidant genes expression and antioxidant enzymes activity were induced. Finally the vitamin E, vitamin C and GSH levels were increased. Our work, proved the renoprotective effects of QE against oxidative stress induced by cisplatin.     

The effects of erdosteine, N-acetylcysteine, and vitamin E on nicotine-induced apoptosis of hippocampal neural cells

This study investigated the frequency of apoptosis in rat hippocampal neural cells after intraperitoneal nicotine injection, examining the roles of the inflammatory markers myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-alpha) in nicotine-induced brain damage and the protective effects of three known antioxidant agents, N-acetylcysteine (NAC), erdosteine, and vitamin E. Female Wistar rats were divided into seven groups, each composed of nine rats: 2 negative control groups, 2 positive control groups, one erdosteine-treated group (500 mg/kg), one NAC-treated group (500 mg/kg), and one vitamin E-treated group (500 mg/kg). Nicotine was intraperitoneally injected at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Apoptosis level in hippocampal neural cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling) method. Staining of cytoplasmic TNF-alpha in hippocampal neural cells and hippocampus MPO activity were evaluated by immunohistochemistry. Nicotine administration had no effect on local TNF-alpha production, or hippocampal MPO activity. The treatments with erdosteine, NAC and vitamin E significantly reduced the rate of nicotine-induced hippocampal neural cell apoptosis. This findings suggest that erdosteine and NAC can be as effective as vitamin E in protecting against nicotine-induced hippocampal neural cell apoptosis.     

Alleviation of lindane induced toxicity in testis of Swiss mice (Mus musculus) by combined treatment with vitamin C, vitamin E and alpha-lipoic acid

Mitigation of lindane induced toxicity in testis of Swiss mice by combined treatment with vitamin C, vitamin E and alpha-lipoic acid has been evaluated. Male healthy mice (40), 8-10 weeks old were randomly selected and divided into 4 groups, control (C); lindane (L); antioxidant (A) and antioxidant plus lindane (A+L). Group C animals were administered only the vehicle (olive oil); in group L lindane was administered orally at a dose of 40 mg/kg body wt.; in group A combination of antioxidants at a dose of 125 mg/kg body wt.(vitamin C: 50 mg/kg body wt., vitamin E: 50 mg/kg body wt. and alpha-lipoic acid: 25 mg/kg body wt.) was administered orally; in group A+L both antioxidants (125 mg/kg body wt.) and lindane (40 mg/kg body wt.) were administered at their respective doses. In group A+L antioxidants were administered 1 h prior to lindane administration. All treatments were continuously given for 60 days. Histopathological changes due to lindane intoxication indicated shrunken and distorted seminiferous tubules, sparse Leydig cells and blood vessels and atrophy in the tissue. The testis weight also decreased significantly. Lindane treated group showed increased lipid peroxidation, whereas glutathione, glutathione peroxidase, superoxide dismutase, catalase and protein were significantly decreased compared to control. Lindane induced damage was minimized by administration of antioxidants. Results suggest that combined pretreatment with antioxidants can alleviate the damage caused to testis by lindane.     

Pro-Leu-glycinamide and its peptidomimetic,PAOPA, attenuate haloperidol induced vacuous chewing movements in rat: A model of human tardive dyskinesia

In the present experimental paradigm, we examine the effect of L-prolyl-L-leucyl-glycinamide (PLG) co-administration with haloperidol on vacuous chewing movements (VCM) in rats-a model of tardive dyskinesia (TD) in humans. We examined the dose dependent induction of VCM through both injected and orally administered PLG (MIF-1). Our results show significant levels of VCM attenuation (P<0.05) in rats treated with 10mg/kg of PLG. Doses of 1 and 100mg/kg were ineffective. Reductions were present in both orally treated and injected rats. We also examined the therapeutic effect of a peptidomimetic of PLG-PAOPA. PAOPA was able to produce similar behavioral effects to PLG at a dose, which was 100-fold lower than the effective dose of PLG. These results suggest that PLG may play a role in D2 receptor expression and function, as well as providing a therapy for neuroleptic induced TD.     

Effect of combined treatment of thioperamide with some antiepileptic drugs on methionine-sulfoximine induced convulsions in mice

Methionine-sulfoximine (MSO), a convulsant is known to increase the activity of histamine N-methyl transferase. The effect of a selective H3 receptor agonist R- (alpha) methylhistamine (RAMH) and antagonist (thioperamide, THP) and some antiepileptic drugs (gabapentin and sodium valproate) have been evaluated on MSO-induced convulsions in mice. The effect of THP was also evaluated in combination with these antiepileptic drugs. Sodium valproate (300 mg/kg, po) and gabapentin (400 mg/kg, po) offered protection against MSO-induced convulsions as evidenced by a significant prolongation of latency to abnormal dorsoflexion and complete protection against mortality within 6 h of administration. THP (15 mg/kg, ip) alone and in combination with sub-effective doses of gabapentin (75 mg/kg, po) and sodium valproate (75 mg/kg, po) revealed no significant differences from the control group or either drug alone. Hence, the convulsant action of MSO does not appear to be mediated via histaminergic mechanisms.     

Dose-dependent modulation of systemic lipid peroxidation and activity of anti-oxidant enzymes by vitamin E in the rat

The objective of this work was to examine the time-dependent pro-oxidant versus antioxidant effect of various doses of vitamin E used commonly in experimental studies. Erythrocyte activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and plasma lipid peroxidation levels were investigated following biweekly intramuscular administration of 100, 300 and 600 mg/kg of vitamin E at a baseline time point, and additionally at 2, 4 and 6 weeks after initiating treatment. Vitamin E had an antioxidant effect when administered at low doses over short time periods, and increased the activity of antioxidant enzymes. At higher doses and over longer time periods, it increased the level of lipid peroxidation, and attenuated the activity of antioxidant enzymes. These results suggest that time-dependent variations in vitamin E effects should be considered in design and interpretation of experimental antioxidant studies, as well as during clinical trials.     

Effect of treatment of cow’s urine “Gomutra” and antioxidants in alleviating the lindane-induced oxidative stress in kidney of Swiss mice (Mus musculus)

The study aimed to evaluate the effect of cow urine and combination of antioxidants against lindane induced oxidative stress in Swiss mice. Male healthy mice, 8–10 weeks old, weighing 30 ± 5 g were randomly selected and divided into eight groups, namely, control (C); lindane (L); antioxidant (A), antioxidant+lindane (A+L), cow urine (U), cow urine+lindane (U+L), cow urine+antioxidants (U+A) and cow urine+antioxidants+lindane (U+A+L). Group C animals were administered only the vehicle (olive oil); doses selected for other treatments were: lindane: 40 mg/kg b.w.; antioxidants: 125 mg/kg b.w. (vitamin C: 50 mg/kg b.w., vitamin E: 50 mg/kg b.w., α-lipoic acid: 25 mg/kg b.w.) and cow urine: 0.25 ml/kg b.w. In group A+L and U+L antioxidants and cow urine were administered 1 h prior to lindane administration and in group U+A and U+A+L cow urine was administered 10 min before antioxidants. All treatments were administered orally continuously for 60 days. Lindane treated group showed increased lipid peroxidation, whereas glutathione, glutathione peroxidase, superoxide dismutase, catalase, protein and endogenous levels of vitamin C and E were significantly decreased compared to control. Administration of cow urine and antioxidants alleviated the levels of these biochemical parameters.     

Dose-dependent modulation of systemic lipid peroxidation and activity of anti-oxidant enzymes by vitamin E in the rat

Abstract

The objective of this work was to examine the time-dependent pro-oxidant versus antioxidant effect of various doses of vitamin E used commonly in experimental studies. Erythrocyte activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and plasma lipid peroxidation levels were investigated following biweekly intramuscular administration of 100, 300 and 600 mg/kg of vitamin E at a baseline time point, and additionally at 2, 4 and 6 weeks after initiating treatment. Vitamin E had an antioxidant effect when administered at low doses over short time periods, and increased the activity of antioxidant enzymes. At higher doses and over longer time periods, it increased the level of lipid peroxidation, and attenuated the activity of antioxidant enzymes. These results suggest that time-dependent variations in vitamin E effects should be considered in design and interpretation of experimental antioxidant studies, as well as during clinical trials.     

Effect of BR-16A (Mentat), a polyherbal formulation on drug-induced catalepsy in mice

Parkinson's disease (PD) is a neurodegenerative disease characterized by the selective loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). The events, which trigger and/or mediate the loss of nigral DA neurons, however, remain unclear. Neuroleptic-induced catalepsy has long been used as an animal model for screening drugs for Parkinsonism. Administration of haloperidol (1 mg/kg, ip) or reserpine (2 mg/kg, ip) significantly induced catalepsy in mice. BR-16A (50 and 100 mg/kg, po), a polyherbal formulation or ashwagandha (50 and 100 mg/kg, po), significantly reversed the haloperidol or reserpine-induced catalepsy. The results indicate that BR-16A or ashwagandha has protective effect against haloperidol or reserpine-induced catalepsy and provide hope that BR-16A could be used in preventing the drug-induced extrapyramidal side effects and may offer a new therapeutic approach to the treatment of Parkinson's disease.