scholarly journals Cardioprotective Activity ofN′′,N′′′-Bis[5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]carbonohydrazide Derivative against Doxorubicin Induced Cardiotoxicity in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-7
Author(s):  
Salma Tabassum ◽  
Kiran Gangarapu ◽  
Gouthami Thumma ◽  
Sarangapani Manda ◽  
Rama Narsimha Reddy Anreddy

The present study was aimed at evaluating the cardioprotective effect of novel syntheticN′′,N′′′-bis[5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]carbonohydrazide derivative, by estimating the various biomarkers like creatine kinase-myoglobin (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and triglycerides (TG) in plasma and antioxidants like catalase, superoxide dismutase in heart tissue homogenate, and histopathological examination of heart tissues. The results showed the significant (P<0.05) dose dependent decrease in elevated cardiotoxic biomarkers CK-MB, LDH, AST, and TG levels. The histopathological studies of heart tissues showed mild degeneration of muscle bundles and less interstitial edematous changes. The results showed the significant (P<0.05) dose dependent increase in antioxidant enzymes catalase and superoxide dismutase in heart tissue homogenates. These observations enable us to conclude thatN′′,N′′′-bis[5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]carbonohydrazide has cardioprotective activity against doxorubicin induced cardiotoxicity.

Author(s):  
K. Amala ◽  
R. Ilavarasan ◽  
R. Arunadevi ◽  
S. Amerjothy

<p><strong>Objective: </strong>The plant of <strong><em>Epaltes</em></strong><strong> <em>divaricata </em>(L.) </strong>Cass.<strong> Traditionally used for jaundice. </strong>The present work aimed to investigate the hepatoprotective activity of alcohol and aqueous extract of the whole plant against paracetamol-induced hepatotoxicity in rats to substantiate its traditional use.</p><p><strong>Methods: </strong>The alcohol and aqueous (200 and 400 mg/kg) extract of <em>Epaltes divaricata</em> prepared by cold maceration were administered orally to the animals with hepatotoxicity induced by paracetamol (1000 mg/kg). Silymarine (40 mg/k) was given as reference standard. Hepatoprotective activity was assessed by estimating marker enzymes and by histopathological studies.</p><p><strong>Results: </strong>Both alcohol and aqueous (200 and 400 mg/kg) extract treatment significantly restored the paracetamol-induced elevations in levels of serum enzymes aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphate (ALP) and total bilirubin in a dose-dependent manner. Histopathological examination revealed that the treatment attenuated the paracetamol-induced damage to the liver. The hepatoprotective effect of both extracts was comparable to that of the standard hepatoprotective agent, silymarin.</p><p><strong>Conclusion: </strong>The alcohol and aqueous extract of <em>E. divaricata</em> exhibited hepatoprotective effect against paracetamol-induced liver damage in rats. This study also validated their traditional medicinal use in jaundice.</p>


1993 ◽  
Vol 265 (1) ◽  
pp. H47-H51 ◽  
Author(s):  
M. R. Glick ◽  
J. D. Gehman ◽  
J. A. Gascho

To determine whether nitric oxide, which is likely endothelium-derived relaxing factor (EDRF), modulates baseline venous tone, the effects of intravenous NG-monomethyl-L-arginine (L-NMMA) (3–25 mg/kg), an EDRF inhibitor, on mean circulatory filling pressure (MCFP) were determined in 10 awake instrumented rats. MCFP, the equilibrated systemic pressure occurring when the circulation is arrested by transient inflation of a balloon in the right atrium, is a measure of total venous capacitance. L-NMMA caused a dose-dependent increase in mean arterial pressure and a dose-dependent decrease in heart rate. MCFP rose from 6.6 +/- 0.2 to 7.6 +/- 0.2 mmHg at the highest L-NMMA dose. The effects of L-NMMA on MCFP were reversed with L-arginine. In an additional four rats, in which hexamethonium was administered to induce ganglionic blockade, L-NMMA (25 mg/kg) caused a similar increase in MCFP (4.1 +/- 0.6 to 5.0 +/- 0.7 mmHg, P = 0.22) during the ganglionic blocked state as during the control unblocked state. These findings suggest that nitric oxide, which is likely EDRF, reduces baseline venous tone.


2004 ◽  
Vol 23 (5) ◽  
pp. 251-256 ◽  
Author(s):  
Mehmet Emin Büyükokuroğlu ◽  
Seyithan Taysi ◽  
Mustafa Buyukavci ◽  
Ebubekir Bakan

Possible preventive effect of dantrolene against the peroxidative damage in rat heart which was induced by the administration of an acute dose of adriamycin (ADR, 20 mg/kg, i.p.) has been examined. Forty-eight hours after ADR administration, biochemical changes including the activities of serum creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) and the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in heart tissue were measured. Pretreatment of rats with dantrolene, given i.p. 30 min prior to ADR injection, substantially reduced the peroxidative damage in the myocardium, and markedly lowered the serum CKMB, LDH and AST. The protective effects obtained by dantrolene administration, however, were not complete and did not reach those of the control group. Dantrolene, at 5 mg/kg, was useful to obtain significant protective effects, while the protector effect of higher dantrolene dosing level (10 mg/kg) was weak or absent. These results suggest that, at least in part, due to antioxidative properties, dantrolene may provide a significant protective effect against acute ADR-induced cardiotoxicity.


Cephalalgia ◽  
1983 ◽  
Vol 3 (1_suppl) ◽  
pp. 139-142 ◽  
Author(s):  
Victor Rizza ◽  
Ennio Bousquet ◽  
Franco Guerrera ◽  
Massimo De Regis

Cerebral tryptophan metabolism was studied in rat brain slices. The results show that serotonin production was inhibited at high levels of tryptophan or 5-oxo-l-prolyltryptophan. In contrast, kynurenine formation showed a dose dependent increase at the various concentrations of tryptophan or 5-oxo-l-prolyltryptophan. Measurements of the activities of tryptophan hydroxylase (TH) and indoleamine 2,3-dioxygenase (IDOase) in crude brain homogenates showed that serotonin formation was linear in the presence of dithiothreitol, whereas kynurenine production was inhibited in the presence of diothiothreitol or superoxide dismutase. These results suggest an inverse relationship in the regulation of 5-hydroxyindole and kynurenine pathways. The former being inhibited in the presence of high tryptophan concentration while the latter is enhanced. Furthermore, a high intracellular thiol-disulphide ratio appears to favour serotonin formation, whereas a highly reducing environment decreases kynurenine production. Nous avons étudié le métabolisme du Trp au mayer de sections de tissu cérébral de rat. Nos résultats montrent que la production de 5-HT est inhibie à hautes concentrations de Trp ou de 5-oxo-l-prolyltryptophane. Au contraire, la production de Kynurenine augmente par rapport à ces concentrations. L'évaluation de l'activité de la TH et de la IDO ase démontre que la production de 5-HT augmente de façon linéaire en presence de di-thio-theréitole tandis que la production de Kinurénine ed inhibite en présence de di-thio-thréitole on super-oxide dismuntase. Ces résultats suggérent une relation inverse dous la régulation du métabolisme du 5-hydroxi-indole er de la Kynurénine: le premier est inhibie en presence de hautes concentrations de Trp tandis que la deuxiéme est stimulée. En ontre, un haut rapport intracellular thide-disulphide semble favoriser la production de 5-HT tandis que une ambiance fort réduisant abaisse la production de Kynurénine. Abbiamo studiato il metabolismo del Trp in sezioni di tessuto cerebrale di ratto. Dai risultati emerge che la produzione di 5-HT viene inibita da alte concentrazioni di Trp o di 5-oxo-l-proliltriptofano. Viceversa la produzione di Kynurenina mostra un incremento dose-dipendente. La valutazione dell-attività della TH e della IDO asi dimostra che la produzione di 5-HT aumenta linearmente in presenza di ditiotreitolo mentre la produzione di Kynurenina viene inibita in presenza di ditiotreitolo o superossido dismutasi. Questi risultati suggeriscono una relazione inversa nella regolazione delle vie metaboliche del 5-idrossi-indolo e della Kynurenina: la prima viene inibita in presenza di alte concentrazioni di Trp, mentre la seconda è potenziata. Inoltre, un alto rapporto intracellulare tiolo-disulfide sembra favorire la produzione di 5-HT mentre un ambiente fortemente riducente abbassa la produzione di Kynurenina.


Author(s):  
Ilochi Ogadinma ◽  
Daniel Yaro Onoja ◽  
Chuemere Arthur Nwafor

The neurodynamic effect of graded hydrocortisone treatment on rhinencephalic and telencephalic brain regions was studied in an experimental animal design that sampled isolated hippocampal, basal nucleic and frontal cortical brain regions of male wistar rats. Four test groups, ii to v were administered 2.5 mg, 5 mg, 7.5 mg and 10 mg respectively. The study period lasted for 6 weeks. Results were statistically analyzed and considered significantly different at a confidence interval of 95%. There was a progressive decline in olfactory response as dose of hydrocortisone treatment was increased. There was a significant dose-dependent decrease in assayed frontal cortical acetylcholine and hippocampal glutamate in brain tissue homogenates. Similar change was observed in brain tissue calcium, magnesium and sodium. For the behavioral, histological and biochemical tests conducted in this study, 6 weeks hydrocortisone treatment showed adverse manifestations from 5 mg, which was more obvious from 7.5 mg. The outcome of this study revealed a possible dose-dependent adverse effect of hydrocortisone on specific brain regions responsible for learning, memory, olfaction and psychosocial behavior.


2009 ◽  
Vol 63 (5-6) ◽  
pp. 341-352
Author(s):  
Dunja Rukavina ◽  
Danica Hasanbasic ◽  
Edin Suljkanovic ◽  
Amela Katica

In this study we investigated the influence of low dosage X - ray irradiation on the incidence of chromosomal damage and changes in mitotic index (MI) in cultured peripheral lymphocytes of the Bosnian and Herzegovinian mountain horse following in vitro irradiation. X-ray irradiation induced a dose-dependent decrease in MI but only the dose of 0.5 Gy induced a significant decrease (p<0.05) in comparison with the control and other dose groups. The analysis of chromosomal damage revealed a clear dose-dependent increase in the incidence of chromosomal damage per metaphase. Significant differences (p<0.05) were detected by analysis of variance and the LSD test confirmed significant differences between cells that received 0.2 Gy and 0.5 Gy when compared to the control cells and cells that received 0.1 Gy. However, Scheeffes' test assigned significance only to the differences established between the cells that received 0.5 Gy and the other groups of lymphocytes. .


2010 ◽  
Vol 30 (5) ◽  
pp. 363-378 ◽  
Author(s):  
Elżbieta Bruchajzer ◽  
Barbara Frydrych ◽  
Stanisław Sporny ◽  
Jadwiga A Szymańska

Until quite recently, pentabromodiphenyl ether (PentaBDE) was most commonly used as a flame retardant. Due to the considerably long atmospheric half-life of PentaBDE and its contribution to environmental pollution, it is categorized as a persistent organic pollutant (POP). As the data on the toxicity of PentaBDE is rather scarce, its potential acute toxicity was the subject of this study. PentaBDE was administered intragastrically to female rats, in a single dose (25, 200 or 2000 mg/kg b.w.). PentaBDE administered to rats disturbed redox homeostasis, which was manifested by lower total antioxidant status (TAS) in serum and by higher liver glutathione reduced (GSH) concentration. The toxic effect of PentaBDE intensified lipid peroxidation. On histopathological examination, administration of the highest PentaBDE dose (2000 mg/kg b.w.) was seen to induce symptoms of fatty liver. PentaBDE caused an increase in relative liver mass, cytochromes P-450 (after two highest doses), a dose-dependent increase in the activity of CYP lA (12—26 fold) and CYP 2B (5—6 fold) as well as the levels of CYP lAl (16—50 fold) and CYP 4A (2—3 fold) in liver.


Author(s):  
Naveen Kumar Bathula ◽  
Bimalendu Choudhary

Background: The botanical Latin name of the plant, Turnera aphrodisiaca, describes its ancient use as an aphrodisiac.Methods: The aim of the present study is to evaluate the protective effect of ethanolic and aqueous extract of Turnera aphrodisiaca leaves against carbon tetrachloride (CCl4)-induced liver damage in male Wistar rats.Results: Administration with ethanolic and aqueous extract of Turnera aphrodisiaca leaves (200 and 400 mg/kg) for 7 days significantly reduced the impact of CCl4 toxicity on the serum markers of liver damage, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in a dose dependent matter. In addition, treatment of both the extracts resulted in markedly increased the levels of superoxide dismutase and catalase enzymes in rats. The histopathological studies in the liver of rats also supported that both extracts markedly reduced the toxicity of CCL4 and preserved the histoarchitecture of the liver tissue to near normal.Conclusion: Thus, the results suggest that ethanolic and aqueous extract of  Turnera aphrodisiaca leaves acts as a potent hepatoprotective agent against CCl4 induced hepatotoxicity in rats.


1994 ◽  
Vol 267 (5) ◽  
pp. F798-F804 ◽  
Author(s):  
J. Gardes ◽  
M. F. Gonzalez ◽  
F. Alhenc-Gelas ◽  
J. Menard

The intervention of the L-arginine-NO pathway in renal vasodilation and renin secretion was studied in an isolated perfused rat kidney model. NG-nitro-L-arginine methyl ester (L-NAME, 1-25 microM), an inhibitor of nitric oxide (NO) synthesis, caused a dose-dependent increase in perfusion pressure (PP) and a dose-dependent decrease in renal perfusate flow. Renin was inhibited independently of the rise in PP, since the effect of L-NAME on renin release was the same when PP was maintained constant. Exposure of rats to low [salt depleted (SD)] or high [salt repleted (SR)] salt intake for 1 mo influenced the renal vascular response to L-NAME (3 microM). Isolated SR rat kidney vasculature vasoconstricted to a greater extent after inhibition of NO synthase than did that of SD kidneys. A similar fall in renin release was observed after L-NAME in both groups, despite a higher renin secretion rate in SD than in SR rats. These results suggest that NO-dependent vasodilation counteracts the renal vasoconstrictor effect of sodium loading.


1993 ◽  
Vol 264 (5) ◽  
pp. G886-G894 ◽  
Author(s):  
P. K. Rangachari ◽  
P. A. Betti

The responses of the canine colonic epithelium to the metabolites of prostaglandin D2 (PGD2) were compared with those elicited by the parent prostanoid. Dose-response relations to PGD2 showed three distinct patterns: 1) a dose-dependent decrease in short-circuit current (Isc) at lower concentrations followed by a dose-dependent increase at higher concentrations; 2) dose-dependent decreases, with no increase even at the highest concentrations tested; and 3) dose-dependent increases in Isc, with no decreases at any concentration. The colon responded differently to the two enzymatically derived metabolites 13,14-dihydro-15-keto-PGD2 (DK) and 11 beta-PGF2 alpha. The former consistently produced only dose-dependent decreases in Isc, while the latter elicited only dose-dependent increases. Pretreatment of tissues with 11 beta-PGF2 alpha altered the responses to PGD2 such that only decreases were noted. Conversely, pretreatment with DK caused PGD2 to elicit only increases in Isc. The nonenzymatically derived PGJ2 elicited responses comparable to those seen with PGD2. Pretreatment of tissues with indomethacin abolished responses to 11 beta-PGF2 alpha as well as its isomer, PGF2 alpha, suggesting the involvement of a cyclooxygenase product. Responses to PGE2 were, however, amplified. Cross-desensitization was noted between the two isomers. Tissues desensitized to either 11 beta-PGF2 alpha or PGF2 alpha were responsive to DK as well as PGE2; however, tissues desensitized to PGE2 were unresponsive to 11 beta-PGF2 alpha. Thus the canine colonic epithelium responds not only to PGD2 but also to its derived metabolites. Variability in the response to PGD2 between animals could stem from differences at the receptor level and/or differential production of these metabolites.


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