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1.

Objective:

To investigate the preventive and curative role of ascorbic acid on doxorubicin (dox)-induced myocardial toxicity in rats.

Materials and Methods:

Animals were divided into five groups of six animals each. Group I served as normal control and received saline 5 ml/kg/day intraperitoneal (i.p.) for a period of 15 days. Group II animals received ascorbic acid 20 mg/kg per oral (p.o.) for 15 days as a pretreatment control (PR). Group III animals received dox 2.5 mg/kg body weight (b.w.), i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg b.w. Group IV animals received ascorbic acid 20 mg/kg p.o. for 15 days as a pretreatment followed by dox 2.5 mg/kg b.w., i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg body weight. Group V animals received dox 2.5 mg/kg b.w., i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg b.w. followed by ascorbic acid 20 mg/kg p.o for 15 days as post-treatment control (CR). The biochemical parameters such as tissue glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), and enzyme biomarkers such as creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were monitored.

Results:

Pretreatment with ascorbic acid (20 mg/kg p.o.) significantly protected the myocardium from the toxic effect of dox (PR), by increasing the levels of antioxidant enzymes such as GSH, SOD, and CAT toward normal and decreased the levels of MDA, CPK, LDH, AST, and ALT as compared with dox-treated rats. Post-treatment with ascorbic acid to dox-treated group (CR) significantly increased the levels of tissue GSH, SOD, CAT and significantly decreased the level of MDA as compared with dox-treated group. It also reduced the severity of cellular damage of the myocardium as confirmed by histopathology. The restoration of the endogenous antioxidant system clearly depicts that ascorbic acid produced its protective effect by scavenging the reactive oxygen species.

Conclusion:

The results obtained in this study provide evidence for the usefulness of the ascorbic acid as a cardioprotective agent.  相似文献   

2.
《Pharmaceutical biology》2013,51(3):339-344
Context: Doxorubicin (Dox) is an anthracycline antibiotic used as anticancer agent. However, its use is limited due to its cardiotoxicity which is mainly attributed to accumulation of reactive oxygen species.

Objective: This study was conducted to assess whether the antioxidant, proanthocyanidins (Pro) can ameliorate Dox-induced cardiotoxicity in rats.

Materials and methods: Male Sprague–Dawely rats were divided into four groups. Group I was control. Group II received Pro (70?mg/kg, orally) once daily for 10 days. Group III received doxorubicin 15?mg/kg i.p. as a single dose on the 7th day and Group IV animals were treated with Pro once daily for 10 days and Dox on the 7th day. The parameters of study were serum biomarkers, cardiac tissue antioxidant status, ECG, and effect on aconitine-induced cardiotoxicity.

Results: Cardiac toxicity of doxorubicin was manifested as a significant increase in heart rate, elevation of the ST segment, prolongation of the QT interval and an increase in T wave amplitude. In addition, Dox enhanced aconitine-induced cardiotoxicity by a significant decrease in the aconitine dose producing ventricular tachycardia (VT). Administration of Pro significantly suppressed Dox-induced ECG changes and normalized the aconitine dose producing VT. The toxicity of Dox was also confirmed biochemically by significant elevation of serum CK-MB and LDH activities as well as myocardial MDA and GSH contents and decrease in serum catalase and myocardial SOD activities. Administration of Pro significantly suppressed these biochemical changes.

Discussion and conclusion: These results suggest that proanthocyanidins might be a potential cardioprotective agent against Dox-induced cardiotoxicity due to its antioxidant properties.  相似文献   

3.
The purpose of the present study was to investigate the cardioprotective effects of Glycyrrhiza uralensis extract (GUE) against doxorubicin (DOX)-induced cardiotoxicity. Imprinting control region (ICR) mice were treated with saline, DOX (20 mg/kg intraperitoneal [ip] for once), GUE (100 mg/kg intragastric [ig] for 8 days), co-treatments with DOX and GUE (100 mg/kg ig for 8 days), and amifostine (100 mg/kg intravenous [iv] for once), respectively. Serum levels of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB), glutathione peroxidase (GSH-P(X)) activity, and glutathione (GSH) level in heart tissue were measured. Histopathologic analysis of heart tissue was also performed. Treatment with GUE significantly protected the mice from DOX-induced cardiotoxicity, indicated by decreased levels of serum LDH and CK-MB, improved heart morphology and increased GSH-P(X) activity and GSH level. Additionally, GUE did not compromise the tumor-inhibitory effect of DOX. In conclusion, our studies imply the potentially clinical application of GUE to overcome the cardiotoxicity of doxorubicin.  相似文献   

4.
Context: Doxorubicin (Dox) is one of the most active chemotherapeutic agents used to treat various types of cancers. Its clinical utility is compromised due to fatal cardiac toxicity characterized by an irreversible cardiomyopathy.

Objective: This study evaluates the cardioprotective potential of naringin (NR) against Dox-induced acute cardiac toxicity in rats.

Materials and methods: Male Wistar rats were randomly divided into five groups. NR (50 and 100?mg/kg) was administered intraperitoneally (i.p.) daily from 0 to 14?d. Doxorubicin (15?mg/kg, i.p.) was given as a single dose on the 10th day. On the 14th day, all animals were sacrificed and oxidative stress parameters that include malondialdehyde (MDA), glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) activities, and all mitochondrial complexes (I-IV) activities were evaluated along with histopathological studies of the heart.

Results: Doxorubicin-induced cardiotoxicity was confirmed by increased (p?<?0.05) MDA, decreased (p?<?0.05) GSH levels, SOD, and CAT activities, mitochondrial complexes (I–IV) activities in the heart tissue. NR (100?mg/kg) showed cardioprotection as evident from significant decreased MDA (p?<?0.001) level, raised (p?<?0.001) GSH level, SOD and CAT activities and increased mitochondrial complexes I (p?<?0.01), II (p?<?0.001), III (p?<?0.001), and IV (p?<?0.05) activities. Further, Dox-induced cardiotoxicity was confirmed by histopathological studies. These obtained results indicated the protective role of NR against Dox-induced cardiac toxicity in rats.

Conclusion: NR can be used in combination with Dox due to its high cardioprotective effect against Dox-induced cardiomyopathy.  相似文献   

5.

Objective:

The objective of this study was to evaluate the cardioprotective effect of herbal bioactive compound ammonium glycyrrhizinate against doxorubicin-induced cardiomyopathy, in experimental animals.

Materials and Methods:

Ammonium glycyrrhizinate (50, 100, 200 mg/kg, p.o.) was administered for four weeks in albino rats. Cardiomyopathy was induced with a dose of 2.5 mg/kg i.p. of doxorubicin on 1th, 7th, 14th, 21th, 28th day in the experimental animals. At the end of the experiment, on 29th day, serum and heart tissues were collected and hemodynamic, biochemical and histopathological studies were carried out.

Results:

Administration of doxorubicin in normal rats showed significant (P < 0.001) changes in body weight, feed intake, urine output, hemodynamic parameters like (blood pressure, heart rate, cardiac output) and in lipid profile (cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein) indicating cardiomyopathy symptoms. Animals treated with ammonium glycyrrhizinate significantly (P < 0.05) decreased triglyceride, cholesterol, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels. Moreover, high density lipoprotein (HDL) levels increased in rats treated with ammonium glycyrrhizinate as compared with the normal group.

Conclusion:

Ammonium glycyrrhizinate is effective in controlling serum lipid profile and cardiac complications in experimentally induced cardiomyopathy in animals.KEY WORDS: Ammonium glycyrrhizinate, cardiac failure, cardiomyopathy, doxorubicin  相似文献   

6.

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 22nd 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.  相似文献   

7.
8.
9.
《Pharmaceutical biology》2013,51(4):377-382
Context: Cardioprotective effects of various plants are generally attributed to their antioxidant activity. The whole fruit extract of pomegranate (WFEP), Punica granatum L. (Punicaceae), has a potent antioxidant activity.

Objective: To investigate cardioprotective effect of WFEP against doxorubicin (Dox)-induced cardiotoxicity in rats.

Materials and methods: Male Wistar rats were divided randomly into three groups of eight rats each: control (water, 5?mL/kg); Dox (10?mg/kg i.v.) and WFEP (100?mg/kg). Dox was administered in Dox and WFEP groups. After anesthetizing the animals on the last day, electrocardiogram was recorded and blood was analyzed for creatine kinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activities. Determinations of superoxide dismutase (SOD), reduced glutathione (GSH), lipid peroxidation (LPO) and histopathology of the heart tissues were carried out.

Results: The WFEP group showed decreased QT and increase in heart rate (p?<?0.05) compared to the Dox group. Significant decrease in CK-MB (p?<?0.01), LDH (p?<?0.05) and no such significant decrease in AST were observed as compared to the Dox group. There was significant increase in the level of GSH (p?<?0.05), whereas inhibition of LPO and increase in SOD concentration was not significant in the WFEP group compared to the Dox group. Histopathological study of the WFEP-treated group showed slight protection against myocardial toxicity induced by Dox.

Conclusion: Results indicate that WFEP has cardioprotective effect against Dox-induced cardiotoxicity in rats.  相似文献   

10.

Objectives:

To investigate the effect of the aqueous extract of Phyllanthus niruri (Aq.E.PN) against doxorubicin (Dox)-induced myocardial toxicity in rats.

Materials and Methods:

Cardiotoxicity was produced by Dox administration (15 mg/kg for 2 weeks). Aq.E PN (200 mg/kg, orally) was administered as pretreatment for 2 weeks alternated with Dox for the next 2 weeks. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH), creatinine phosphokinase (CPK) and alkaline phosphatase, diagnostic enzyme markers like aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and antioxidants such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were monitored after 3 weeks of the last dose.

Results:

Pretreatment with the Aq.E.PN significantly (P < 0.01) protected the myocardium from the toxic effects of Dox by reducing the elevated level of biomarker and diagnostic enzymes like LDH, CPK, AST and ALT to the normal levels. Aq.E PN increased the GSH, SOD and CAT levels and decreased the MDA levels in cardiac tissue. Administration of Dox caused cardiomyopathy associated with an antioxidant deficiency.

Conclusion:

These results suggest a cardioprotective effect of P. niruri due to its antioxidant properties.  相似文献   

11.
The present study evaluated the ameliorative potential of hydroalcoholic extract of Trichosanthes dioica root (TDA) against arsenic induced toxicity in male albino rats. TDA (5 and 10mg/kg) was administered orally to rats for 20 consecutive days before oral administration of sodium arsenite (10mg/kg) for 8 days. Then the body weights, organ weights, haematological profiles, serum biochemical profile; hepatic and renal antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and DNA fragmentation were evaluated. Pretreatment with TDA markedly and significantly normalized body weights, organ weights, haematological profiles, serum biochemical profile and significantly modulated all the hepatic and renal biochemical parameters and reduced DNA fragmentation in arsenic intoxicated rats. The present findings conclude that T. dioica root possessed remarkable ameliorative effect against arsenic induced organ toxicity in male albino rats mediated by alleviation of arsenic induced oxidative stress by multiple mechanisms.  相似文献   

12.
Toxic effects of beryllium salts on the reproductive organs of cyclic adult female albino rats have been studied. An attempt was made to overcome these effects using an Ayurvedic medicien Liv-52 (Himalaya Drug Co., Bombay). Liv-52-primed rats (1 mL/rat/day for 15 days) were exposed to beryllium nitrate intravenously and were sacrificed at different time intervals. At autopsy ovary, uterus, cervix, and vagina were processed for biochemical and histophatologic examination. Histoarchitecture of the ovary, uterus, cervix, and vagina revealed severe necrotic changes with beryllium nitrate treatment. Tissue glycogen content and the activity of alkaline phosphatase were inhibited significantly after beryllium treatment. Total and esterified cholesterol levels increased significantly in these organs when exposed to beryllium salts. However, a significant improvement was observed in the biochemical parameters and histoarchitecture of these organs when beryllium was injected into Liv-52-primed animals.  相似文献   

13.

Objectives:

This study is designed to evaluate the cardioprotective effect of fenugreek on isoproterenol- induced myocardial infarction and is investigated by an in vivo method in rats.

Materials and Methods:

Male Wistar albino rats were divided into four groups (n=10). Group I received 0.5% CMC treated as normal control group. Group II received isoproterenol (85 mg/kg body weight) intraperitoneal (i.p.) for two consecutive days (14th and 15th days). Group III received fenugreek (250 mg/kg body weight) intragastric intubation for 15 days. Group IV rats received fenugreek as in Group III and additionally isoproterenol was given for two consecutive days (14th and 15th days).

Results:

The results described the cardioprotective effect that observed in Group IV showed significantly (P< 0.05) decreased levels of TBARS and enhanced the activities of both enzymatic and non-enzymatic antioxidants (SOD, CAT, GPx and GSH) in myocardial infarcted rats when compared to Groups II and III. Histopathological studies were also co-relating with the above biochemical parameters.

Conclusion:

These findings concluded the cardioprotective effect of fenugreek on lipid peroxidation and antioxidant defense system during isoproterenol-induced myocardial infarction in rats.  相似文献   

14.
目的 探讨芒果苷(MGF)预处理对大鼠心肌缺血再灌注(MI/R)损伤的保护作用及机制。方法 SD大鼠随机分为5组,即假手术组、模型组和MGF高、中、低剂量(40、20、10 mg/kg)组,采用结扎左冠脉前降支30 min再灌注2 h的方法制备大鼠MI/R损伤模型,于术前7 d开始ig给药。采用比色法测定血清肌酸激酶(CK)和乳酸脱氢酶(LDH)活性,ELISA法测定血清肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平;染色法测定心肌梗死面积(MIS);取心肌匀浆,比色法测定髓过氧化物酶(MPO)活性。结果 与模型组比较,MGF高、中剂量组MIS、血清LDH活性显著降低(P<0.05);MGF各剂量组血清CK活性、血清TNF-α和IL-1β水平、心肌MPO活性明显降低(P<0.05、0.01)。结论 MGF预处理通过抑制中性粒细胞浸润,下调TNF-α和IL-1β表达,抑制炎症反应,发挥对MI/R所致心肌损伤的保护作用。  相似文献   

15.

Objective:

The objective of this study is to evaluate the effect of ethanolic extract of Urtica parviflora Roxb. in isoproterenol (ISO) induced myocardial infarction (MI) in rats.

Materials and Methods:

U. parviflora Roxb. (350 mg/kg and 500 mg/kg, p.o) was administered for 15 days in rats. MI was induced with a single dose of ISO (200 mg/kg, s.c.) on the 14th and 15th day. At the end of the experimental period (i.e., on the day 16), serum and heart tissues were collected and total cholesterol (TC), high density lipoprotein, triglyceride and malondialdehyde, superoxide dismutase, catalase (CAT), reduced glutathione (GSH) and body weight were determined.

Results:

Administration of ISO in control rats showed a significant (P < 0.001) increase serum cholesterol alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and low density lipoprotein (LDL). There was a significant increase (P < 0.01) in the levels of heart tissues as compared with respective control groups. Rats treated with U. parviflora significantly (P < 0.01) decreased ALT, AST, ALP, LDL and TC. Moreover, there was an increased CAT and GSH levels in rat treated with U. parviflora Roxb. as compared with the control group.

Conclusion:

U. parviflora (350 and 500 mg/kg p.o.) is effective in controlling serum LDL levels and reduced cardiac complication in experimentally induced MI in rats.KEY WORDS: Cardioprotective activity, isoproterenol, myocardial infarction, Urtica parviflora Roxb  相似文献   

16.
This study was designed to investigate the therapeutic effect of sodium formononetin-3'-sulphonate (Sul-F), a water-soluble derivate of formononetin, on acute myocardial infarction in rats. The results showed that treatment with Sul-F significantly prevented the elevation of ST-segment level, decreased the contents of creatine kinase-MB, lactate dehydrogenase, alanine aminotransferase and cardiac troponin T in serum and reduced the myocardium necrosis scores. The number of apoptosis cardiocytes is well accordance with the up-regulated expression of Bcl-2 and the down-regulated expression of Bax. Meanwhile, Sul-F significantly increased the cardiac mitochondrial ATP content, improved ATP synthase activity, decreased thiobarbituric acid-reactive substances content and attenuated the decrease in superoxide dismutase and glutathione peroxidase activities. These findings indicate that Sul-F has a protective potential against myocardial infarction injury. A possible mechanism for the protective effect is the elevated expression of endogenous antioxidant defence enzymes degraded lipid peroxidation products and improved energy metholism of cardiac mitochondrial, thus attenuating cardiocyte apoptosis.  相似文献   

17.
目的研究阿托伐他汀(ATO)对多柔比星(DOX)所致心肌损伤大鼠心脏氧化应激的改善作用。方法将60只大鼠随机分为对照组、模型组,ATO低、中、高(2、6、18mg/kg)剂量组,每组12只,除对照组外其余大鼠腹腔注射DOX(2.5mg/kg),隔天1次,共给药6次制备心肌毒性模型,最后一次注射DOX后,ATO低、中、高(2、6、18mg/kg)剂量组灌胃给予相应剂量药物,每天1次,8周后生化分析仪检测大鼠血清肌酸激酶(CK)、乳酸脱氢酶(LDH)活性,比色法检测血清脑钠肽(BNP)和心肌丙二醛(MDA)含量,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,心肌一氧化氮(NO)含量,一氧化氮合酶(NOS)、过氧化脂(LPO)和过氧化氢酶(CAT)的活性,苏木精-伊红(HE)染色检测心肌病理组织学变化。结果与对照组相比,模型组血清CK、LDH和BNP明显升高(P<0.05),心肌中NO含量、NOS、GSH-Px、CAT和SOD活性明显下降、MDA、LPO含量明显升高(P<0.05),心肌病理损伤严重。与模型组相比,ATO 18mg/kg组血清CK、LDH和BNP明显下降(P<0.05),心肌中NO含量、NOS、GSH-Px、CAT和SOD活性明显上升,MDA、LPO含量明显下降(P<0.05),心肌病理损伤减轻。结论 ATO对DOX所致大鼠心肌损伤具有改善作用,起保护作用可能与提高心肌抗氧化应激损伤有关。  相似文献   

18.
Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.  相似文献   

19.
《Pharmaceutical biology》2013,51(4):482-487
Context: The heart is one of the target organs susceptible to attack by sepsis, and protection of the cardiac function in sepsis or alleviation dysfunction caused by sepsis appears a serious and urgent problem.

Objective: This study was designed to explore the effect of curcumin on myocardial injury induced by sepsis and to explore the therapeutic effect of curcumin in managing sepsis induced cardiac dysfunction.

Methods: Cecal ligation and puncture surgery were used to establish the sepsis model. Curcumin was administered by peritoneal injection (200?mg/kg/d, 3 days). The effects of curcumin on the cardiac functions [Ejection Fraction (EF), Fractional Shortening (FS), Cardiac Output (CO), Heart Rate (HR)], body temperature, cTn I and superoxide dismutase levels, malondialdehyde content (an index of lipid peroxidation), and myocardial histopathological and ultrastructural studies were carried out.

Results: We demonstrated that treatment of rats with curcumin significantly decreased elevated levels of cTn I and MDA (p < 0.05) in plasma, and increase the levels of SOD (p < 0.05) after CLP. Moreover, curcumin markedly enhanced the myocardial contractility by increasing the decreased EF and FS in rats with sepsis induced by CLP (p < 0.05). In addition, curcumin could alleviate the myocardial inflammation and structure damage of myocardial cells in sepsis induced by CLP.

Conclusion: In conclusion, the results from the present study demonstrate that curcumin has the protective effects on cardiac function in rats with sepsis and curcumin could be considered as an effective and safe therapeutic agent for the management of sepsis induced cardiac dysfunction.  相似文献   

20.
OBJECTIVE: The major objective of the present study was to examine the cardioprotective effect of resveratrol, an antioxidant presents in red wine, in the rat after ischemia-reperfusion (I/R). DESIGN: The left coronary artery was in occlusion for 30 min followed by a 120 min reperfusion in anesthetized rats. Animals were pretreated with and without resveratrol before occlusion. The post-ischemic ventricular function (left ventricle maximum systolic pressures and the maximal first derivative of developed pressure) and myocardial infarct size and myocardial nitric oxide (NO) and malonaldehyde (MDA) content were compared. RESULTS: Resveratrol pretreatment had dramatic cardioprotective effects on post-ischemic ventricular functional recovery and decreasing myocardial infarct size. Resveratrol pretreatment also increased NO and decreased MDA content in myocardium. CONCLUSIONS: Resveratrol has cardioprotective properties in I/R rats. The cardioprotective effects in the I/R rats may be correlated with its antioxidant activity and upregulation of NO production.  相似文献   

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