Protective effect of Nardostachys jatamansi on oxidative injury and cellular abnormalities during doxorubicin-induced cardiac damage in rats

Nardostachys jatamansi is a medicinally important herb of Indian origin. It has been used for centuries in the Ayurvedic and Unani systems of medicine for the treatment of various ailments. We have evaluated the effect of N. jatamansi (rhizomes) on the biochemical changes, tissue peroxidative damage and abnormal antioxidant levels in doxorubicin (adriamycin)-induced cardiac damage. Preliminary studies on the effect of the graded dose of extract showed that 500 mg kg(-1) orally for seven days was found to be optimum and hence all further study was carried out with this particular dose. Rats administered doxorubicin (15 mg kg(-1), i.p.) showed myocardial damage that was manifested by the elevation of serum marker enzymes (lactate dehydrogenase, creatine phosphokinase, aspartate aminotransaminase and alanine aminotransaminase). The animals showed significant changes in the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase) and lipid peroxidation levels. Pretreatment with N. jatamansi extract significantly prevented these alterations and restored the enzyme activity and lipid peroxides to near normal levels. Restoration of cellular normality accredits the N. jatamansi with a cytoprotective role in doxorubicin-induced cardiac damage.     

Preventive effects of N-acetyl cysteine on lipids, lipoproteins and myocardial infarct size in isoproterenol induced myocardial infarcted rats: an in vivo and in vitro study

The present study evaluated the preventive effects of N-acetyl cysteine in isoproterenol induced myocardial infarcted rats. Rats were pretreated with N-acetyl cysteine (10 mg/kg body weight) daily for a period of 14 days. After pretreatment, rats were injected with isoproterenol (100 mg/kg body weight) at an interval of 24 h for two days to induce myocardial infarction. Isoproterenol induced myocardial infarction was indicated by increased activity of creatine kinase-MB and levels of cardiac troponins in the serum. The weight of heart and the levels of serum and heart cholesterol, triglycerides, free fatty acids were increased in isoproterenol induced myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased high density lipoprotein cholesterol. It enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase and the levels of lipid peroxidation products. Pretreatment with N-acetyl cysteine showed significant preventive effects in all the biochemical parameters studied in myocardial infarcted rats. Also, N-acetyl cysteine reduced myocardial infarct size. Histopathological findings of N-acetyl cysteine pretreated myocardial infarcted heart correlated with these biochemical findings. The in vitro study confirmed the strong antioxidant action of N-acetyl cysteine. Thus, the present study revealed that N-acetyl cysteine prevented increased heart weight, accumulation of lipids, altered levels of lipoproteins thereby reducing myocardial infarct size due to its antilipidemic and antioxidant effects in isoproterenol induced myocardial infarcted rats. This study may have a significant impact on myocardial infarction.     

Attenuation of abnormalities in the lipid metabolism during experimental myocardial infarction induced by isoproterenol in rats: beneficial effect of ferulic acid and ascorbic acid

The present study aims at evaluating the effect of the combination of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism. The rats were divided into eight groups: Control, isoproterenol, ferulic acid alone, ascorbic acid alone, ferulic acid+ascorbic acid, ferulic acid+isoproterenol, ascorbic acid+isoproterenol and ferulic acid+ascorbic acid+isoproterenol. Ferulic acid (20 mg/kg b.w.t.) and ascorbic acid (80 mg/kg b.w.t.) both alone and in combination was administered orally for 6 days and on the fifth and the sixth day, isoproterenol (150 mg/kg b.w.t.) was injected intraperitoneally to induce myocardial injury to rats. Induction of rats with isoproterenol resulted in a significant increase in the levels of triglycerides, total cholesterol, free fatty acids, free and ester cholesterol in both serum and cardiac tissue. A rise in the levels of phospholipids, lipid peroxides, low density lipoprotein and very low density lipoprotein-cholesterol was also observed in the serum of isoproterenol-intoxicated rats. Further, a decrease in the level of high density lipoprotein in serum and in the phospholipid levels, in the heart of isoproterenol-intoxicated rats was observed, which was paralleled by abnormal activities of lipid metabolizing enzymes: total lipase, cholesterol ester synthase, lipoprotein lipase and lecithin: cholesterol acyl transferase. Pre-cotreatment with the combination of ferulic acid and ascorbic acid significantly attenuated these alterations and restored the levels to near normal when compared to individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism.     

Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids

Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro. Long-term oral administration of PGF extract (500 mg kg(-1)) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholesterol in Zucker diabetic fatty (ZDF) rats, indicating improvement by PGF extract of abnormal cardiac TG accumulation and hyperlipidemia in this diabetic model. Treatment of ZDF rats with PGF extract lowered plasma FA levels. Furthermore, the treatment suppressed cardiac overexpression of mRNAs encoding for FA transport protein, peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase alpha2, and restored downregulated cardiac acetyl-CoA carboxylase mRNA expression in ZDF rats, whereas it showed little effect in Zucker lean rats. The results suggest that PGF extract inhibits increased cardiac FA uptake and oxidation in the diabetic condition. PGF extract and its component oleanolic acid enhanced PPAR-alpha luciferase reporter gene activity in human embryonic kidney 293 cells, and this effect was completely suppressed by a selective PPAR-alpha antagonist MK-886, consistent with the presence of PPAR-alpha activator activity in the extract and this component. Our findings suggest that PGF extract improves abnormal cardiac lipid metabolism in ZDF rats by activating PPAR-alpha and thereby lowering circulating lipid and inhibiting its cardiac uptake.     

Efficacy of grape seed proanthocyanidins on serum and heart tissue lipids in rats subjected to isoproterenol-induced myocardial injury

The present study was aimed to evaluate the preventive role of grape seed proanthocyanidins (GSPs) on serum and tissue lipid enzymes in isoproterenol (ISO)-induced myocardial injury in male Wistar albino rats. GSP was administered orally to rats (150-180 g) in three different doses, by gastric gavage (50, 100 and 150 mg/kg GSP), 6 days a week for 5 weeks. At the end of this period, all the rats, except the normal untreated rats that served as the control group, were administered ISO, 85 mg/kg subcutaneously, for 2 consecutive days to induce myocardial injury. After 48 h, rats (n=6 per group) were anesthetized with anesthetic ether, sacrificed and the levels of biochemical observations of the serum and heart tissues were performed. Biochemical assessment of myocardial injury was done by measuring the activities of serum thiobarbituric acid reactive substances and plasma lactate, which were significantly elevated in the rats administered with ISO. Further, our results suggest that prior administration of GSPs significantly maintained the cholesterol, phospholipids, triglycerides, and free fatty acids levels in serum and heart tissue of the ISO-induced myocardial injury in rats. The experiments conclude that GSPs possess cardioprotective and hypolipidemic effect on the treatment of ISO-induced myocardial injury.     

Procyanidins Produce Significant Attenuation of Doxorubicin‐Induced Cardiotoxicity via Suppression of Oxidative Stress

Abstract: Doxorubicin is widely prescribed in the chemotherapy of haematological malignancies and solid tumours. The major side effect of doxorubicin is oxidative injury‐related cardiotoxicity, which has dramatically hindered its usage. Procyanidins from grape seeds are potent free radical scavengers that have been shown to protect against anthracycline‐induced cardiotoxicity. In the present study, we tested whether procyanidins would prevent the doxorubicin‐induced cardiotoxicity in rats. Rats were intraperitoneally treated with doxorubicin at a cumulative dose of 15 mg/kg with and without pre‐administration of procyanidins. Our data showed that doxorubicin led to cardiac function deterioration, myocardial injury and increased oxidative stress in cardiac tissues. The cardiac function deterioration by doxorubicin included increased QT‐interval and ST‐interval in electrocardiograph (ECG) and decreased left ventricular developed pressure. Doxorubicin‐induced myocardial injury was shown by the increased creatine kinase, alanine aminotransferase and aspartate aminotransferase in serum as well as in myocardial lesions. Pretreatment with procyanidin (150 mg/kg daily) effectively hindered the adverse effects of doxorubicin, such as myocardial injury and impaired heart function. Procyanidin pretreatment attenuated cytoplasmic vacuolization, increased left ventricular developed pressure and improved the ECG. The cardioprotective effect of procyanidin corresponded to the decrease of lipid peroxidation and the increase of cardiac antioxidant potency in doxorubicin‐treated rats that were also given procyanidin. An in vitro cytotoxic study showed that procyanidins did not attenuate the antineoplastic activity of doxorubicin to A549 adenocarcinoma cells. All the above lines of evidence suggest that procyanidins protect cardiomyocytes from doxorubicin‐induced cardiotoxicity via suppression of oxidative stress.     

Up-regulation of the cardiac lipid metabolism at the onset of heart failure

Chronic pressure overload and atherosclerosis are primary etiologic factors for cardiac hypertrophy and failure. However, mechanisms underlying the transition from hypertrophy to heart failure are incompletely understood. We analyzed the development of heart failure in mice with chronic pressure overload induced by aortic constriction and compared the results with aged apolipoprotein E-deficient mice suffering from advanced atherosclerosis. We combined cardiac function analysis by echocardiography and invasive hemodynamics with a comprehensive microarray gene expression study (GSE25765-8). The microarray data showed that the onset of heart failure induced by pressure overload or advanced atherosclerosis was accompanied by a strong up-regulation of key lipid metabolizing enzymes involved in fat synthesis, storage and oxidation. Cardiac lipid overload may be involved in the progression of heart failure by enhancing cardiomyocyte death. Up-regulation of the cardiac lipid metabolism was related to oxygen and ATP depletion of failing hearts because anti-ischemic treatment with ranolazine normalized the cardiac lipid metabolism and improved cardiac function. Vice versa, inhibition of cellular respiration and ATP generation by mild thiol-blocking with cystamine triggered the cardiac lipid metabolism and caused signs of heart failure. Cardiac tissue specimens of patients with heart failure also showed high protein levels of key fat metabolizing enzymes as well as lipid accumulation. Taken together, our data strongly indicate that up-regulation of the cardiac lipid metabolism and myocardial lipid overload are underlying the development of heart failure.     

Hypolipidaemic effects of Curcuma longa L and Nardostachys jatamansi, DC in triton-induced hyperlipidaemic rats

Fifty per cent ethanolic extract of Curcuma longa (tuber) and Nardostachys jatamansi (whole plant) feeding elevates HDL-cholesterol/total cholesterol ratio. The extracts also caused a significant reduction in the ratio of total cholesterol/phospholipids. Curcuma longa exhibited better cholesterol and triglyceride lowering activity [Ch = -85%; Tg = -88%] as compared to N. jatamansi in triton-induced hyperlipidaemic rats. In view of the protective action of HDL against heart disease and atherogenecity, C. longa consumption is recommended.     

基于药动学及代谢物组学研究多柔比星在大鼠体内的心脏毒性

目的 测定多柔比星大剂量给药后原型药物及代谢产物的药动学特征及组织分布,以明确代谢产物在多柔比星急性心脏毒性中的作用。方法 测定多柔比星血清及心脏组织源性代谢物的变化特点,寻找与心脏毒性发生相关的代谢生物标志物及心脏毒性的潜在机制。利用LC-MS/MS测定多柔比星及多柔比星醇的浓度,利用GC-MS进行血清及心脏组织的代谢物组学分析。结果 多柔比星大鼠体内单剂量给药后,在心脏组织呈现高分布,且高剂量（10 mg·kg^-1）时分布显著增加。多柔比星醇的代谢转换率很低,且在心脏组织中的分布较低。代谢物组学研究结果表明,小分子能量物质酮体及脂肪酸为血清样本中的主要差异性物质。心脏组织中主要差异性物质为脂肪酸和甘油单酯。结论 多柔比星单剂量给药后,其在心脏中分布较高,且高剂量时特异性分布增加。多柔比星醇在血清及心脏组织中的浓度较低,推测其在急性毒性中的作用有限。多柔比星单剂量给药会引起心脏组织内的以脂质代谢为主的能量代谢异常,能量代谢对多柔比星相关的急性心肌毒性具有重要作用。     

Effect of alpha-tocopherol on lipid peroxidation in isoproterenol induced myocardial infarction in rats

The effect of alpha-tocopherol pretreatment on lipid peroxidation and antioxidant status in isoproterenol induced myocardial infarction was studied in rats. Isoproterenol administered rats showed a significant increase in lipid peroxides in serum, heart and aorta. A significant increase in serum iron level with a significant decrease in iron binding capacity was also observed. The levels of antioxidants such as ceruloplasmin, glutathione and the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase decreased significantly in isoproterenol administered rats when compared to control. The activity of Na+K+ATPase decreased significantly and the activity of Ca2+ATPase increased significantly in heart and aorta of isoproterenol administered rats. alpha-tocopherol pretreated rats maintained the levels of antioxidants, membrane bound enzymes and activities of antioxidant enzymes near normal, on isoproterenol administration, thus establishing its effect as an antioxidant.     

天芝草胶囊对阿霉素的减毒作用研究

目的:研究天芝草胶囊对阿霉素的减毒作用。方法:给予肝癌H22荷瘤小鼠天芝草胶囊和阿霉素,观察小鼠生长状况,并考察给药后小鼠心电图、心肌酶谱和心肌形态的变化。结果:天芝草胶囊可对抗阿霉素所致心室动作电位除极不同步,抑制血清乳酸脱氢酶的升高,对抗阿霉素导致的心肌损伤。结论:天芝草胶囊对阿霉素具有减毒作用。     

Attenuation by Nardostachys jatamansi of 6-hydroxydopamine-induced parkinsonism in rats: behavioral, neurochemical, and immunohistochemical studies

Parkinson's disease (PD) is one of the commonest neurodegenerative diseases, and oxidative stress has been evidenced to play a vital role in its causation. In the present study, we evaluated whether ethanolic extract of Nardostachys jatamansi roots (ENj), an antioxidant and enhancer of biogenic amines, can slow the neuronal injury in a 6-OHDA-rat model of Parkinson's. Rats were treated with 200, 400, and 600 mg/kg body weight of ENj for 3 weeks. On day 21, 2 microl of 6-OHDA (12 microg in 0.01% in ascorbic acid-saline) was infused into the right striatum, while the sham-operated group received 2 microl of vehicle. Three weeks after the 6-OHDA injection, the rats were tested for neurobehavioural activity and were sacrificed after 6 weeks for the estimation of lipid peroxidation, reduced glutathione content, the activities of glutathione-S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase, quantification of catecholamines, dopaminergic D2 receptor binding and tyrosine hydroxylase expression. The increase in drug-induced rotations and deficits in locomotor activity and muscular coordination due to 6-OHDA injections were significantly and dose-dependently restored by ENj. Lesioning was followed by an increased lipid peroxidation and significant depletion of reduced glutathione content in the substantia nigra, which was prevented with ENj pretreatment. The activities of glutathione-dependent enzymes, catalase and superoxide dismutase in striatum, which were reduced significantly by lesioning, were dose-dependently restored by ENj. A significant decrease in the level of dopamine and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, and both were significantly recovered following ENj treatment. All of these results were exhibited by an increased density of tyrosine hydroxylase immunoreactive (TH-IR) fibers in the ipsilateral striatum of the lesioned rats following treatment with ENj; 6-OHDA injection had induced almost a complete loss of TH-IR fibers. This study indicates that the extract of Jatamansi might be helpful in attenuating Parkinsonism.     

Green tea extract impedes dyslipidaemia and development of cardiac dysfunction in streptozotocin-diabetic rats

1. The efficacy of green tea extract (GTE) on serum and cardiac lipids was investigated in streptozotocin (STZ)-diabetic rats. 2. Diabetes was induced in rats by a single intraperitoneal injection of STZ (60 mg/kg bodyweight). Six weeks after the induction of diabetes, GTE was administered orally for 4 weeks (300 mg/kg bodyweight daily). Bodyweight, heart weight, heart weight : bodyweight ratio, blood glucose, serum and cardiac lipids were determined in experimental rats. 3. In diabetic rats, there was a significant decrease in bodyweight with an increase in heart weight : bodyweight ratio and blood glucose. Diabetic rats had significantly increased serum levels of cholesterol, triglycerides, free fatty acids and low-density lipoprotein-cholesterol (LDL-C) and decreased levels of high-density lipoprotein-cholesterol (HDL-C). In the hearts of diabetic rats, there was a significant increase in cholesterol, triglycerides and free fatty acids levels, with an increase in lipoprotein lipase activity. 4. The administration of GTE to diabetic rats resulted in significant recovery in bodyweight, heart weight : bodyweight ratio and blood glucose levels. The administration of GTE reduced cholesterol, triglyceride, free fatty acid and LDL-C levels, and increased HDL-C levels, in the serum of diabetic rats. In addition, GTE decreased cholesterol, triglyceride, free fatty acids levels and lipoprotein lipase activity in the myocardium of diabetic rats. These beneficial effects of GTE are ascribed to its antihyperglycaemic and hypolipidaemic activity. In conclusion, green tea can reduce the risk of cardiovascular disease in diabetes with a significant improvement in lipid metabolism.     

Protective effects of berberine against doxorubicin-induced cardiotoxicity in rats by inhibiting metabolism of doxorubicin

Abstract

1.?The clinical use of doxorubicin, an effective anticancer drug, is severely hampered by its cardiotoxicity. Berberine, a botanical alkaloid, has been reported to possess cardioprotective and antitumor effects. In this study, we investigated the cardioprotective effect of berberine on doxorubicin-induced cardiotoxicity and the effect of berberine on the metabolism of doxorubicin.

2.?Adult male Sprague-Dawley rats were administered doxorubicin in the presence or absence of berberine for 2 weeks. Administration of berberine effectively prevented doxorubicin-induced body weight reduction and mortality in rats.

3.?Berberine reduced the activity of myocardial enzymes, including aspartate aminotransferase (AST), creatine kinase (CK), CK isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Echocardiographic examination further demonstrated that berberine effectively ameliorated cardiac dysfunction induced by doxorubicin.

4.?Berberine inhibited the metabolism of doxorubicin in the cytoplasm of rat heart and reduced the accumulation of doxorubicinol (a secondary alcohol metabolite of doxorubicin) in heart.

5.?These data showed that berberine alleviated the doxorubicin-induced cardiotoxicity in rats via inhibition of the metabolism of doxorubicin and reduced accumulation of doxorubicinol selectively in hearts.     

Effect of the joint administration of ketamine and propofol on the lipid metabolism and peroxidation in rats

Ketamine (50 mg/kg, i.p.) increases the intensity of lipolysis and lipid peroxidation (LPO) in the hepatic and cardiac tissues of Wistar male rats, as manifested by an increase in the content of nonetherified fatty acids and cholesterol in the blood serum and in the content of LPO products in the blood serum and in the liver and heart tissues. Propofol in the same dose also influences the lipid metabolism and LPO intensity, but to a lower extent. The joint administration of both ketamine (25 mg/kg, i.p.) and propofol (25 mg/kg, i.p.) leads to averaging of some characteristics of the lipid metabolism and LPO.     

Ameliorating effect of capsaicin on alterations in lipid metabolism during mice lung carcinoma

Spices and vegetables possess antioxidant activity that can be applied for preservation of lipids and lower lipid peroxidation in biological systems. In the present study, we have investigated the effect of capsaicin on lipid metabolism during benzo(a)pyrene induced lung cancer in Swiss albino mice. Benzo(a)pyrene (50 mg/kg wt) induced lung cancer animals showed abnormal changes in the tissue and serum lipids, lipoproteins and lipid metabolizing enzymes. Treatment with capsaicin (10 mg/kg body wt) remarkably attenuated all the above alterations and restored normalcy. These findings reveal the chemomodulatory potential of capsaicin in attenuating the alterations in lipid metabolism during experimental lung carcinogenesis.     

Taurine deficiency and doxorubicin: interaction with the cardiac sarcolemmal calcium pump

An anticancer drug, doxorubicin, and a naturally occurring beta-amino acid, taurine, exert opposing actions on myocardial calcium content and lipid peroxidation. Thus, we tested the hypothesis that the two agents may interact to modify cardiac calcium metabolism and indices of lipid peroxidation. Cardiac taurine levels were reduced by half in rats given tap water containing a beta-amino transport inhibitor, beta-alanine. Taurine deficiency was associated with an increased susceptibility of the heart to doxorubicin-mediated calcium accumulation, a phenomenon commonly associated with doxorubicin cardiotoxicity. Taurine deficiency also predisposed the heart to enhanced formation of malondialdehyde caused by doxorubicin administration. While increases in malondialdehyde levels are often associated with lipid peroxidation, the failure of doxorubicin to cause changes in oxidized glutathione content makes peroxidative mechanisms a less likely explanation for the potentiation of doxorubicin-mediated myocardial calcium accumulation in taurine-deficient rats. A more likely possibility is the interaction between taurine deficiency and doxorubicin to inhibit the sarcolemmal calcium pump. The data also suggest that the interaction between doxorubicin and taurine deficiency does not involve alterations in the pharmacokinetics of doxorubicin or the cardiotoxic metabolite, doxorubicinol. It is concluded that reduction in sarcolemmal calcium pump activity by taurine deficiency may contribute to myocardial calcium accumulation in hearts whose calcium homeostasis has been compromised by doxorubicin.     

Cardioprotective effects of zofenopril, a new angiotensin-converting enzyme inhibitor, on doxorubicin-induced cardiotoxicity in the rat

We have studied the effect of zofenopril, a new angiotensin-converting enzyme inhibitor in preventing cardiac injury induced by chronic doxorubicin treatment in rats. Cardiac function was assessed by measuring changes in electrocardiogram (ECG) tracings, haemodynamics and cardiac responses in vivo to isoprenaline, 4 weeks after suspension of doxorubicin treatment, in vehicle-treated rats and in animals receiving zofenopril (15 mg/kg/os/day) alone, doxorubicin (1.5 mg/kg i.v. once a week for 5 weeks) or zofenopril+doxorubicin treatment. Doxorubicin induced a significant lengthening of the QalphaT interval, which was completely prevented by zofenopril treatment. The cardiac positive inotropic effect induced by i.v. isoprenaline was selectively depressed by doxorubicin (no changes in chronotropic responses) and this adverse effect of doxorubicin was also prevented in zofenopril+doxorubicin pretreated rats. Doxorubicin induced a significant increase in relative heart weight, which was likewise prevented in zofenopril+doxorubicin treated rats. In separate experiments, zofenopril did not interfere with the antitumor activity of doxorubicin (inhibition of tumor growth in nude mice xenografted with A2780 human tumor line). In conclusion, the oral administration of zofenopril is able to significantly ameliorate, up to 4 weeks after the end of doxorubicin administration, doxorubicin-induced cardiotoxicity without affecting the antitumor activity of this anthracycline.     

羟苯氨酮对实验性心肌缺血的治疗作用

目的研究强心扩血管新药羟苯氨酮(oxyphenamone)对心肌缺血的治疗作用。方法用多导生理记录仪和电磁流量计测定心脏血流动力学参数，观察药物对阻断冠脉致急性心肌梗死猫心脏生理功能的影响。形成异丙肾上腺素致大鼠心肌缺血坏死模型，从心肌酶学及病理形态学方面评价药效。结果羟苯氨酮(2-8 mg·kg^-1,iv)可剂量依赖性地降低心梗猫的心率、血压、血管阻力与张力时间指数(TTI)，轻度增加心肌收缩力与心输出量，不影响左室压与心脏作功。羟苯氨酮(4-8 mg·kg^-1,ip)可明显减轻异丙肾上腺素致大鼠心肌肌酸磷酸激酶(CPK)、丙二醛(MDA)与血清谷草转氨酶(GOT)活性变化与病理形态学损伤。结论羟苯氨酮对心肌缺血性损伤有明显治疗作用。