Protective effect of ethyl acetate fraction of Rhododendron arboreum flowers against carbon tetrachloride-induced hepatotoxicity in experimental models

Objective:

To evaluate the hepatoprotective potential of ethyl acetate fraction of Rhododendron arboreum (Family: Ericaceae) in Wistar rats against carbon tetrachloride (CCl₄)-induced liver damage in preventive and curative models.

Materials and Methods:

Fraction at a dose of 100, 200, and 400 mg/kg was administered orally once daily for 14 days in CCl₄-treated groups (II, III, IV, V and VI). The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (SALP), γ-glutamyltransferase (γ -GT), and bilirubin were estimated along with activities of glutathione S-transferase (GST), glutathione reductase, hepatic malondialdehyde formation, and glutathione content.

Result and Discussion:

The substantially elevated serum enzymatic activities of SGOT, SGPT, SALP, γ-GT, and bilirubin due to CCl₄ treatment were restored toward normal in a dose-dependent manner. Meanwhile, the decreased activities of GST and glutathione reductase were also restored toward normal. In addition, ethyl acetate fraction also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl₄-intoxicated rats in a dose-dependent manner. Silymarin used as standard reference also exhibited significant hepatoprotective activity on post-treatment against CCl₄-induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that ethyl acetate fraction has a potent hepatoprotective action against CCl₄-induced hepatic damage in rats.     

Sex and age-related differences in aminopyrine N-demethylase activity in DA- and Wistar-strain rat liver microsomes. Effect of ovariectomy

1. Liver microsomal mixed-function oxidase components were studied in Wistar and Dark Agouti (DA) rats (4-45 weeks) with regard to sex- and age-related differences. Total cytochrome P-450 ranged from 0.29 to 1 nmol/mg in Wistar rats and from 0.21 to 1.27 nmol/mg in DA rats, males had higher levels than females (P<0.0025). Cytochrome b₅ ranged between 0.42-1.37 nmol/mg and 0.42-1.56 nmol/mg in Wistar and DA strains, respectively, and NADPH-reductase activity ranged between 14-43 and 11-46 nmol/min per mg (Wistar and DA respectively).

2. Significant age-related differences were found in DA rats with four- to six-fold increase in N-demethylase activity from young to adult rats. Sex-related differences were found in both Wistar- and DA-strain rats, with males having higher (about twice) metabolic activity than females. In contrast, no significant sex- or age-related differences in cytochrome ₅ content, or NADPH-reductase activity, were found.

3. Ovariectomy of 10-13-week-old females did not affect N-demethylase activity, cytochrome P-450, cytochrome b₅ or NADPH-reductase activity in Wistar or DA rats.

4. Cytochrome P-450 content did not correlate (r = 0.35) with aminopyrine N-demethylase activity.

5. Results indicate that sex- and age-related differences are due to changes in the isozymic composition of cytochrome P-450, and that these changes are not subject to oestrogen regulation.     

Polyamines: Potential anti-inflammatory agents and their possible mechanism of action

Objective:

To evaluate the anti-inflammatory activity of exogenously administered polyamines on experimentally induced acute and chronic inflammation in wistar rats and to elucidate their possible mechanism of action.

Materials and Methods:

The in vivo anti-inflammatory activity of polyamines was studied using acute (carrageenin paw edema), sub-acute (cotton pellet granuloma) and chronic (Freund''s adjuvant induced arthritis) models of inflammation. The biochemical parameters like liver lipid peroxides, SGOT and SGPT were also measured.

Results:

Polyamines exhibited significant anti-inflammatory activity in acute, sub-acute and chronic models of inflammation. Polyamines treatment inhibited the increase in lipid peroxides in liver and the serum concentration of marker enzymes (glutamate oxaloacetate transferase and glutamate pyruvate transferase) during inflammation.

Conclusion:

Polyamines possess anti-inflammatory activity in acute and chronic inflammation which can be attributed to their anti-oxidant and /or lysosomal stabilization properties.     

Amelioration effects against N-nitrosodiethylamine and CCl(4)-induced hepatocarcinogenesis in Swiss albino rats by whole plant extract of Achyranthes aspera

Objective:

The prevalence of oxidative stress may be implicated in the etiology of many pathological conditions. Protective antioxidant action imparted by many plant extracts and plant products make them a promising therapeutic drug for free-radical-induced pathologies. In this study, we assessed the antioxidant potential and suppressive effects of Achyranthes aspera by evaluating the hepatic diagnostic markers on chemical-induced hepatocarcinogenesis.

Materials and Methods:

The in vivo model of hepatocarcinogenesis was studied in Swiss albino rats. Experimental rats were divided into five groups: control, positive control (NDEA and CCl₄), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks after the administration of NDEA and CCl₄, treated rats received A. aspera extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end of 24 weeks, the liver and relative liver weight and body weight were estimated. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were also assayed, and the histopathological studies were investigated in control, positive control, and experimental groups.

Results:

The extract did not show acute toxicity and the per se effect of the extract showed decrease in LPO, demonstrating antioxidant potential and furthermore no change in the hepatic diagnosis markers was observed. Administration of AAE suppressed hepatic diagnostic and oxidative stress markers as revealed by decrease in NDEA and CCl₄ -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO. There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and GSH as observed after AAE treatment. The liver and relative liver weight were decreased after treatment with AAE in comparison to positive control group. The architecture of hepatic tissue was normalized upon treatment with extract at different dose graded at 100, 200, and 400 mg/kg. b.w. in comparison to positive control group.

Conclusion:

These results suggest that A. aspera significantly alleviate hepatic diagnostic and oxidative stress markers which signify its protective effect against NDEA and CCl⁴-induced two-stage hepatocarcinogenesis.     

Altered activity of hepatic mixed-function mono-oxygenase enzymes in streptozotocin-induced diabetic rats.

1. In streptozotocin-induced diabetic male rats, hepatic microsomal aminopyrine N-demethylase activity was depressed, whereas aniline hydroxylase activity and cytochrome P-450 content were increased over control values. 2. In diabetic female rats, hepatic microsomal aminopyrine N-demethylase activity, aniline hydroxylase activity, biphenyl 4-hydroxylase activity, and cytochrome P-450 content were increased over control values. 3. Insulin treatment of diabetic male and female rats antagonized all physical and biochemical abnormalities of the diabetic state; 4. Methyl analogues of streptozotocin did not produce a diabetic state when injected into female rats, and resulted in no changes in aminopyrine N-demethylase activity, aniline hydroxylase activity, or cytochrome P-450 content. 5. Insulin treatment of non-diabetic female rats resulted in slight decreases in aminopyrine N-demethylase and aniline hydroxylase activities, but no changes in cytochrome P-450 content. These observations suggest that insulin primarily influences drug metabolism of diabetic animals through correction of the insulin-deficient diabetic state.     

Interaction of endosulfan and dietary vitamin A on rat hepatic drug metabolising enzymes

The effect of interaction of Endosulfan, a chlorinated insecticide of the cyclodiene group, with dietary vitamin A on the hepatic mixed function oxidase system in rats has been studied. Endosulfan administration (ten days) significantly increased microsomal protein content and cytochrome P-450 levels, NADPH cytochrome C-reductase aminopyrine N-demethylase and aniline hydroxylase activities, with respect to control rats. Administration of vitamin A (10,000 I.U./100 g body weight) daily for ten days reduced the activity of the above mentioned enzymes, when vitamin A and endosulfan were given together, vitamin A reduced the endosulfan induced increase of microsomal proteins and cytochrome P-450 levels, the activity of NADPH cytochrome C-reductase, aminopyrine N-demethylase and aniline-hydroxylase.     

Olanzapine-induced hepatopathy in albino rats: A newer model for screening putative hepatoprotective agents, namely silymarin

Backgrounds:

This study was conducted to establish olanzapine-induced hepatopathy in Wistar albino rats as a newer model to screen putative hepatoprotective agents namely silymarin.

Materials and Methods:

Albino rats were divided into three groups, namely vehicle control group (CG), olanzapine-treated group (OZ), and olanzapine plus silymarin (OZS) treated groups. Both the OZ and OZS groups were treated with the same dose of intraperitoneal olanzapine for 6 weeks and group OZS additionally received oral silymarin. Baseline and terminal hepatic enzymes (SGOT, SGPT, and ALP) were measured in all three groups.

Results:

Histopathological examination of livers of both OZ and OZS groups showed degenerative changes, whereas those of control group showed normal architecture. Liver enzyme levels showed statistically significant rise in comparison to the control group as well as the respective base line values in both the test groups, but the differences in the rise of liver enzymes between the two test groups were not statistically significant.

Conclusion:

Olanzapine-induced hepatopathy in rats can be used as a model for screening putative hepatoprotective agents and in our setting silymarin has failed to provide any hepatoprotection.     

Is cytochrome modulation the new frontier for decreasing the risk of cataract?

Aim:

The present study was designed to study the effect of cytochrome P450 (CYP) modulators on the occurrence of cataract using male Sprague-Dawley rats weighing 40:50 gm.

Materials and Methods:

Macroscopical examination of the lens isolated from rats pretreated with diltiazem (30 mg/kg; once daily; PO) showed delayed occurrence of cataract while pioglitazone (3.8 mg/kg; once daily; PO) pretreatment demonstrated an early cataract.

Results and Conclusion:

A delayed occurrence of cataract with diltiazem (CYP inhibitor) and an early onset of cataract with pioglitazone (CYP inducer) indicate that a cytochrome P450 mediated pathway may affect the initiation of cataract but not the maturation pattern.     

Antidiabetic and vasoprotective activity of lithium: Role of glycogen synthase kinase-3

Objectives:

Lithium is a drug of choice in maniac disorder. Lithium inhibits the glycogen synthase kinase-3 (GSK-3), an enzyme involved in the insulin signalling pathway. Elevated levels of GSK-3 were found in diabetic rats and humans. We aimed to determine the effect of lithium chloride in diabetes and associated vascular complications in diabetic rats.

Materials and Methods:

Type 2 diabetes was induced by high fat diet and low dose of streptozotocin. Diabetic rats were divided into diabetic control and lithium chloride treatment groups. Lithium chloride was used as a GSK-3 inhibitor. The treatment was given for 4 weeks. Various biochemical parameters were measured before initiation and the end of treatment. Systolic blood pressure was measured by the non-invasive tail-cuff method, while various biochemical and tissue parameters were estimated for efficacy. Vasoreactivity was performed by taking the contractile response of H₂O₂ (10^-6 M to 10^-3M) and angiotensin II (10^–11 to 10^–7 M) in rat thoracic aortas of different groups. Statistical comparisons between all groups were performed by using two tailed one-way ANOVA followed by the Dunnett test. P-values <0.05 were considered statistically significant.

Results:

Treatment with lithium chloride significantly reduced the augmented systolic blood pressure, various biochemical parameters, and antioxidant parameters in diabetic-treated rats. Treatment also showed the decrease in augmented responses of H₂O₂ and angiotensin II in rat thoracic aortas of treated rats.

Conclusions:

We can conclude that lithium chloride treatment reduces the diabetic state as well as diabetes-induced vascular dysfunction.     

Contrasting effects of ethylenethiourea on hepatic monooxygenases in rats and mice

The effects of ethylenethiourea (ETU) on the hepatic xenobiotic metabolizing system in rats and mice were investigated. Male rats and male mice were given oral doses of 50 and 75, or 50, 75, 100, 500, and 1,000 mg/kg for 3 days. The microsomal enzymes studied were aminopyrine N-demethylase, aniline hydroxylase, and cytochrome P-450. In rats, the activity of aminopyrine N-demethylase was reduced to values between 60 and 70% of controls 24 h after treatment. A decrease in aniline hydroxylase activity and cytochrome P-450 content was observed on the 3rd day after exposure. In mice, treatment with ETU resulted in an increase of cytochrome P-450 at all dose levels. The activity of aniline hydroxylase was significantly elevated in the groups receiving doses of 100 mg/kg and higher. Aminopyrine N-demethylase was unaffected by the treatment. The results suggest that there are qualitative differences between rats and mice after ETU exposure with respect to the response of the hepatic monooxygenases.     

Role of an Ethanolic Extract of Crotalaria juncea L. on High-Fat Diet-Induced Hypercholesterolemia

Objective

To evaluate the antihypercholesterolemic effects of 50 mg/kg BW and 100 mg/kg BW per day of an ethanolic extract of Crotalaria juncea Linn (whole plant) by performing in vivo studies.

Methods

The effects of oral administration of 50 mg/kg BW and 100 mg/kg BW per day of an ethanolic extract of Crotalaria juncea Linn (whole plant) in rats fed with a high-fat diet were investigated by evaluating parameters like food consumption, weight gain, fecal fat excretion, serum and liver lipids, and biochemical profiles as well as by histopathological studies. The results were compared to animals fed with the standard diet and animals fed with a high-fat diet and atorvastatin (10 mg/kg BW).

Results

The animal group administered with the ethanolic extract for 35 days showed decreased levels of TC, LDL, VLDL, TG, HDL+VLDL, VLDL+LDL, LDL/TC, AI, SGOT, SGPT, and elevated levels of HDL, HDL/TC, significantly (p<0.01 & p<0.05) in a dose-dependent manner. The evaluation of liver tissues of the animal groups treated with the herbal extract and standard had shown increased levels of SOD, GSH, and catalase, whereas levels of SGOT, SGPT, total glucose, HMG-CoA, lipase, amylase, and the percentage of malon-dialdehyde were decreased when compared with the high-fat diet-fed rats. Body weight and food intake in the treated groups were significantly lower than that in the model control.

Conclusion

The present study showed that an ethanolic extract of Crotalaria juncea L. influences several blood lipid and metabolic parameters in rats, suggesting a potential benefit as an antihypercholesterolemic agent.     

Association between progesterone binding and cytochrome P-450 content of hepatic microsomes in the rat treated with cobalt-haem

The effect of cobalt protoporphyrin IX (Co-haem) given to male rats in single subcutaneous doses (25-100 mumol/kg body wt.) was studied. Co-haem decreased cytochrome P-450 content and aminopyrine N-demethylase activity, but increased progesterone content and 3H-progesterone binding in a dose-related manner. The effect of a single dose of 50 mumol/kg body wt. was reversible; cytochrome P-450 and progesterone content, and progesterone binding, returned to the normal level 24-40 d after injection but aminopyrine N-demethylase activity was only partially restored. The converse actions of Co-haem on microsomal progesterone and cytochrome P-450 content showed high correlation.     

Cardioprotective effect of methanolic extract of Ixora coccinea Linn. leaves on doxorubicin-induced cardiac toxicity in rats

Objectives:

To investigate the effect of methanolic extract of Ixora coccinea Linn. (MEIC) leaves against doxorubicin-induced cardiac toxicity in rats.

Material and Methods:

Albino Wistar rats were pretreated with the methanolic extract of Ixora coccinea Linn. leaves (200 and 400 mg/kg, orally) for 1 week followed with the simultaneous treatment with doxorubicin (cumulative dose of 15 mg/kg in six divided doses for 2 weeks) along with the extracts for the next 14 days. On the 22^nd day hemodynamic parameters such as blood pressure and ECG were recorded. Biochemical study including biomarkers like creatine kinase – MB (CK – MB), lactate dehydrogenase (LDH), SGOT and SGPT, tissue antioxidant markers viz. catalase (CAT), superoxide dismutase (SOD) and extent of lipid peroxidation viz. malondialdehyde (MDA) was estimated. Histopathology of heart was also done to assess the cardioprotective effect.

Results:

Pretreatment with MEIC significantly reduced (P<0.01) the ST segment elevation and also maintained the BP (P<0.01) close to normal. The MEIC significantly reduced the elevated level of biomarkers like CK - MB, LDH, SGOT, SGPT (P<0.01) near to normal, the MEIC also increased the tissue antioxidant markers viz. CAT, SOD and decreased the level of MDA (P<0.01) in cardiac tissue by dose-dependant manner. The histopathology of heart also further confirmed the cardioprotection provided by the methanolic extract of Ixora coccinea Linn. leaves.

Conclusion:

The results suggest a cardioprotective effect of Ixora coccinea Linn. leaves due to its antioxidant properties.KEY WORDS: Antioxidant, blood pressure, cardiotoxicity, electrocardiography, Ixora coccinea Linn.     

Hepatic drug metabolism after phenobarbital and diphenylhydantoin administration in the rat--influence of vitamin D3 status.

Measurements of aniline hydroxylation, aminopyrine N-demethylation and cytochrome P-450 content after a 3-week treatment with phenobarbital (PB), diphenylhydantoin (DPH) or a combination of the two drugs were undertaken during normal vitamin D status (D +) and vitamin D deficiency (D ?) with or without vitamin D₃(D₃) supplementation. Serum calcium concentrations were reduced after D deprivation but responded by a significant increase toward normal values to a single pharmacological dose of D₃. Serum phosphorus concentrations were also slightly raised by the supplementation. Even in the presence of higher cytochrome P-450 content in D ? rats, aniline hydroxylase and aminopyrine N-demethylase activities were lower in D ? than in D + animals. These two enzymatic parameters, as well as cytochrome P-450 content, were increased by anticonvulsant (ACV) drug treatment regardless of the D nutritional status. The in vivo hexobarbital sleeping time was shortened by ACV drugs but the sleeping time tended to be longer in D ? than in D + rats. Supplementation with 1000 I.U. of D₃, lowered aniline hydroxylase activity both in D + and D? animals; the supplementation had no effect on aminopyrine N-demethylase activity in D + animals but had an inhibitory effect after PB and a stimulatory effect after DPH treatment in D? animals. Cholecalciferol supplementation lowered cytochrome P-450 content toward normal values in D? rats while it had no effect in D + animals. These observations suggest that (1) PB and DPH pretreatment do not alter the normal response of serum calcium and phosphorus to a single pharmacological dose of D₃; (2) in a state of vitamin D deficiency accompanied by hypocalcemia, the inducing capacity of PB and DPH on the liver mixed function oxidase system is not lost; (3) under certain circumstances, vitamin D₃, can influence the catalytic activity of the mono-oxygenase complex; (4) cytochrome P-450 is influenced by vitamin D deficiency and/or changes in extracellular calcium but the forms induced by PB and DPH may not necessarily be the ones specifically involved in vitamin D metabolism.     

Effect of sizofilan, an immunomodulator, on hepatic microsomal mixed-function oxidase activities in rats

Mixed-function oxidase activities of hepatic microsomal preparations from rats were examined after intraperitoneal administration of sizofilan (SPG), an immunomodulator. Repeated doses of SPG (3 mg/kg/12 hr, 4 times) depressed the hepatic cytochrome P-450 content and the activities of aminopyrine N-demethylase and aniline hydroxylase.     

Effects of pravastatin on the pharmacokinetic parameters of nimodipine after oral and intravenous administration in rats: Possible role of CYP3A4 inhibition by pravastatin

Objective:

The aim of this study was to investigate the effects of pravastatin on the pharmacokinetics of nimodipine in rats.

Materials and Methods:

The effect of pravastatin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Nimodipine was administered to rats intravenously (3 mg/kg) and orally (12 mg/kg) with pravastatin (0.3 and 1 mg/kg).

Results:

Pravastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with a 50% inhibition concentration (IC₅₀) of 14 µM. Compared with the oral control group, the area under the plasma concentration-time curve (AUC_0-∞) of nimodipine was increased significantly. Consequently, the absolute bioavailability (AB) of nimodipine with pravastatin (1 mg/kg) was 31.1%, which was significantly enhanced compared with the oral control group. Moreover, the relative bioavailability (RB) of nimodipine was 1.12- to 1.31-fold greater than that of the control group.

Conclusions:

The enhanced oral bioavailability of nimodipine might be mainly due to inhibition of the CYP3A-mediated metabolism of nimodipine in the small intestine and/or in the liver and due to reduction of the total body clearance rather than both to inhibition of the P-gp efflux transporter in the small intestine and reduction of renal elimination of nimodipine by pravastatin. The increase in the oral bioavailability of nimodipine with pravastatin should be taken into consideration of potential drug interactions between nimodipine and pravastatin.KEY WORDS: Bioavailability, CYP3A4, nimodipine, P-gp, pharmacokinetics, pravastatin     

Hepatoprotective activity of aqueous extract of Portulaca oleracea in combination with lycopene in rats

Objective:

To investigate the hepatoprotective activity of the aqueous extract of the aerial parts of Portulaca oleracea (P. oleracea) in combination with lycopene against carbon tetrachloride induced hepatotoxicity in rats.

Materials and Methods:

Hepatotoxicity was induced in male Wistar rats by intraperitoneal injection of carbon tetrachloride (0.1 ml/kg b.w for 14 days). The aqueous extract of P. oleracea in combination with lycopene (50 mg/kg b.w) was administered to the experimental animals at two selected doses for 14 days. The hepatoprotective activity of the combination was evaluated by the liver function marker enzymes in the serum [aspartate transaminases (AST), alanine transaminases (ALT), alkaline phosphatase (Alk.P), total bilirubin (TB), total protein (TP) and total cholesterol (TC)], pentobarbitone induced sleeping time (PST) and histopathological studies of liver.

Results:

Both the treatment groups showed hepatoprotective effect against carbon tetrachloride induced hepatotoxicity by significantly restoring the levels of serum enzymes to normal which was comparable to that of silymarin group. Besides, the results obtained from PST and histopathological results also support the study.

Conclusions:

The oral administration of P. oleracea in combination with lycopene significantly ameliorates CCl₄ hepatotoxicity in rats.     

Differential acute effects of phenobarbital and 3-methylcholanthrene pretreatment on CCl 4 -induced hepatotoxicity in rats

Phenobarbital (PB) pretreatment significantly enhanced the rise in SGOT and SGPT activity immediately after a 3 hr exposure of rats to CCl₄ by inhalation. However, these parameters of hepatotoxicity were significantly lower in rats pretreated with 3-methylcholanthrene (MC) when compared to rats pretreated with the vehicle and exposed to CCl₄ vapor. Hepatic microsomal NADPH cytochrome c reductase activity and the amount of CO-binding pigment were elevated by PB pretreatment, but MC had no effect on hepatic microsomal NADPH cytochrome c reductase activity. Although CCl₄ exposure reduced CO-binding pigment content by 61% in PB pretreated and by 39% in MC-pretreated rats, microsomal NADPH cytochrome c reductase activity was reduced by only 6% and 20%, respectively. At 21 hr after exposure to CCl₄, the difference in SGOT and SGPT values of the PB and MC pretreated rats was more divergent. Histologic evidence at this time revealed extensive damage in the PB pretreated animals and a sparing effect in the MC pretreated animals. The differential effects of MC and PB pretreatment on NADPH cytochrome c reductase activity and CO-binding pigment content may be responsible for the observed protective effect of MC in CCl₄ exposed rats.     

Increased endothelin-1 vasoconstriction in mesenteric resistance arteries after superior mesenteric ischaemia-reperfusion

BACKGROUND AND PURPOSE

Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone. We aimed to evaluate the influence of superior mesenteric artery (SMA) ischaemia-reperfusion (I/R) on mesenteric resistance artery vasomotor function and the mechanism involved in the changes in vascular responses to ET-1.

EXPERIMENTAL APPROACH

SMA from male Sprague-Dawley rats was occluded (90 min) and following reperfusion (24 h), mesenteric resistance arteries were dissected. Vascular reactivity was studied using wire myography. Protein and mRNA expression, superoxide anion (O₂^•−) production and ET-1 plasma concentration were evaluated by immunofluorescence, real-time quantitative PCR, ethidium fluorescence and elisa, respectively.

KEY RESULTS

I/R increased ET-1 plasma concentration, ET-1-mediated vasoconstriction and ET_B mRNA expression, and down-regulated ET_A mRNA expression. Immunofluorescence confirmed mRNA results and revealed an increase in ET_B receptors in the mesenteric resistance artery media layer after I/R. Therefore, the ET_B receptor agonist sarafotoxin-6 induced a contraction that was inhibited by the ET_B receptor antagonist BQ788 only in vessels, with and without endothelium, from I/R rats. Furthermore, BQ788 potentiated ET-1 vasoconstriction only in sham rats. Endothelium removal in rings from I/R rats unmasked the inhibition of ET-1 vasoconstriction by BQ788. Endothelium removal, N^ω-nitro-L-arginine methyl ester and superoxide dismutase abolished the differences in ET-1 vasoconstriction between sham and I/R rats. We also found that I/R down-regulates endothelial NOS mRNA expression and concomitantly enhanced O₂^•− production by increasing NADPH oxidase 1 (NOX-1) and p^47phox mRNA.

CONCLUSIONS AND IMPLICATIONS

Mesenteric I/R potentiated the ET-1-mediated vasoconstriction by a mechanism that involves up-regulation of muscular ET_B receptors and decrease in NO bioavailability.     

Anticataleptic and antiepileptic activity of ethanolic extract of leaves of Mucuna pruriens: A study on role of dopaminergic system in epilepsy in albino rats

Objective:

To assess the anticataleptic and antiepileptic activity of leaves of Mucuna pruriens in albino rats.

Materials and Methods:

Haloperidol-induced catalepsy (HIC), maximum electro-shock (MES) method, pilocarpine-induced Status epilepticus (PISE) and single-dose effect of M. pruriens were employed.

Results:

M. pruriens (100 mg/kg) had significant anticataleptic and antiepileptic activity in HIC, MES, and PISE.

Conclusions:

M. pruriens extract has the potential to be an anticataleptic and antiepileptic drug. Dopamine and 5-HT may have a role in such activity.