Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propolis (bee glue) is one of the major hive products of bees and is rich in flavonoids, which are known for antioxidant activities. Doxorubicin-induced myocardiopathy is the consequence of oxidative stress through the mediation of free radicals. The effect of intraperitoneal administration of propolis (50 and 100 mg/kg) was studied on cardiomyopathy produced by doxorubicin (10 mg/kg, i.v.) in rats. Serum creatine phosphokinase (CK), aspartate aminotransferase (AST), blood and tissue glutathione (GSH), and thiobarbituric acid reactive substances (TBARS) in heart were estimated to assess the status of heart muscle. An elevation of the levels of CK, AST, GSH, and TBARS was observed following doxorubicin treatment. Parallel experiments with a pretreatment of propolis significantly reduced the levels of these parameters . Biochemical observations were supplemented by histopathological examination of heart sections. The protective effect of propolis was compared with that of rutin, a known cardioprotective flavonoid. The study demonstrates the cardioprotective effect of propolis in doxorubicin-induced experimental cardiotoxicity.
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PMID:Propolis protects against doxorubicin-induced myocardiopathy in rats. 861 23

Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme into biliverdin, carbon monoxide, and iron. HO-1, an inducible form, is thought to contribute to resistance to various types of oxidative stress. Doxorubicin (DOX) produces clinically useful responses in a variety of human cancers. We reported previously that prior administration of DOX ameliorated subsequent hepatic ischemia and reperfusion injury. The aim of this study was to examine whether this pharmacological preconditioning was useful for another type of hepatic injury induced by a non-surgical method. When a high dose of DOX (10 mg/kg body weight) was administered directly to rat liver via the portal vein, serum aspartate transaminase (AST) and alanine transaminase (ALT) levels increased markedly 24 hr after the injection. Under this condition, zinc-protoporphyrin IX, a specific inhibitor of HO-1, caused both serum AST and ALT levels to be elevated further. When a low dose of DOX (5 mg/kg body weight) was administered to rats via the tail vein as pharmacological preconditioning 3 days before the injection of a high dose of DOX via the portal vein, the levels of serum AST and ALT in rats clearly were improved as compared with rats without the preconditioning. Expression of HO-1 in the liver was confirmed 3 days after the administration of a low dose of DOX. In addition, prior administration of zinc-protoporphyrin IX abolished the effect of DOX preconditioning. Immunohistochemical analysis showed that the positive staining of HO-1 protein induced by a low dose of DOX was localized to histiocytes infiltrating periportal areas. These results strongly suggest that pharmacological preconditioning with DOX may generally help to attenuate subsequent oxidant-induced hepatic injury.
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PMID:Pharmacological preconditioning with doxorubicin. Implications of heme oxygenase-1 induction in doxorubicin-induced hepatic injury in rats. 1170 58

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 CK-MB, 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.
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PMID:Prevention of acute adriamycin cardiotoxicity by dantrolene in rats. 1522 3

Oleuropein (oleu) is a natural phenolic antioxidant, which is present in elevated concentration in olives, olive oil and olive tree leaves. Doxorubicin (DXR) induced cardiotoxicity is mainly induced by oxidative stress but the precise mechanism remains obscure. However, there is evidence that high concentration of nitric oxide (NO) occurring as a result of iNOS induction and peroxynitrite formation may be involved in DXR cardiotoxicity. The aim of the present study was to evaluate a possible protective role of oleu in DXR induced cardiotoxicity in vivo. Fifty rats were divided into 6 groups and treated as follows: control group with a single injection of 2 ml normal saline intraperitoneally (i.p.), DXR group with a single dose of 20 mg/kg i.p, and DXR plus oleu groups with 20 mg/kg DXR i.p. and 100 or 200 mg/kg/BW of oleu i.p. for 5 or 3 consecutive days starting either 2 days before or on the day of DXR administration. Seventy-two hours after DXR treatment blood samples were collected for creatine phosphokinase (CPK), creatine phosphokinase-MB (CPK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) assessments and the rats were then sacrificed. Hearts were used for general histology, iNOS immunohistochemical and Western blot analysis, and for determination of tissue concentrations of lipid peroxidation products, protein carbonyls (PCs), and nitrotyrosine (NT). DXR treated animals demonstrated very extensive cytoplasmic vacuolisation whereas much less vacuolisation was found in oleu treated groups. They also revealed a significant elevation of cardiac enzymes release into systemic circulation (P<0.05 vs saline). Both doses of Oleu tested and both treatment protocols reduced DXR elevated serum levels of CPK, CPK-MB, LDH, AST and ALT (P<0.05). Furthermore, it reduced DXR induced lipid peroxidation, PCs content, NT concentration and iNOS induction in myocardial tissue (P<0.05). Oleu exerts a protective effect by eliminating DXR induced cardiotoxicity expressed by the alteration of intracellular and peripheral markers. Combined oleu and DXR treatment improves the therapeutic outcome by preventing undesirable toxicity.
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PMID:Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of oxidative and nitrosative stress. 1722 28

Doxorubicin is an anthracycline antibiotic agent used in the treatment of a variety of solid and haematopoietic tumours, but its use is limited by formation of metabolites that induce acute and chronic cardiac toxicities. Angelica sinensis has been widely used to treat cardiovascular and cerebrovascular diseases in China. In the present study, we used an in vivo mouse model to explore whether A. sinensis could protect against doxorubicin-induced chronic cardiotoxicity. Male ICR mice were treated with distilled water or water extraction of A. sinensis (15 g/kg, orally) daily for 4 weeks, followed by saline or doxorubicin (15 mg/kg, intravenously) treatments weekly. Cardiotoxicity was assessed by electrocardiograph, antioxidant activity in cardiac tissues, serum levels of creatine kinase, aspartate aminotransferase (AST) and histopathological change in cardiac tissues. A cumulative dose of doxorubicin (60 mg/kg) caused animal death and myocardial injury characterized by increased QT interval and decreased heart rate in electrocardiograph, decrease of heart antioxidant activity, increase of serum AST, as well as myocardial lesions. Pre-treatment with A. sinensis significantly reduced mortality and improved heart performance of the doxorubicin-treated mice as evidenced from normalization of antioxidative activity and serum AST, preventing loss of myofibrils as well as improving arrhythmias and conduction abnormalities. Furthermore, the in vitro cytotoxic study showed that A. sinensis did not compromise the antitumour activity of doxorubicin. These results suggested that A. sinensis elicited a typical cardioprotective effect on doxorubicin-related oxidative stress, and could be a novel adjunct in the combination with doxorubicin chemotherapy.
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PMID:Angelica sinensis: a novel adjunct to prevent doxorubicin-induced chronic cardiotoxicity. 1797 Oct 65

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.
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PMID:Procyanidins produce significant attenuation of doxorubicin-induced cardiotoxicity via suppression of oxidative stress. 1914 57

Doxorubicin is one of the most active cytotoxic agents in current use. The clinical usefulness of the doxorubicin has been precluded by its marked cardiotoxicity. The aim of the present study was to investigate the effect of Khamira Abresham Hakim Arshadwala, a well known unani cardiac tonic formulation, pre-treatment on doxorubicin-induced cardiotoxicity, and nephrotoxicity in rats. Twenty-four Wistar albino rats, divided into four groups, were used. Khamira Abresham Hakim Arshadwala was administered daily, for 7 days, and a single dose of doxorubicin (10 mg/kg, i.v.) on day 5. After 48 h of doxorubicin injection, animals were sacrificed. Lactate dehydrogenase (LDH), aspartate transaminase (AST), blood urea nitrogen (BUN), and creatinine were estimated in the serum. Heart specimens were used for biochemical estimations of lipid peroxides (MDA), reduced glutathione (GSH), catalase, and for microscopic examination of histopathological changes. Doxorubicin showed cardiotoxicity and nephrotoxicity, as evidenced by elevated activities of AST, LDH, BUN, creatinine, and MDA, depletion in GSH level, and catalase activity. Histopathological studies showed disruption of cardiac tissues in doxorubicin groups. Khamira Abresham Hakim Arshadwala pre-treatment showed a protective effect against the enzymatic changes in serum as well as cardiac and kidney tissue damage, significantly. The present findings suggest that Khamira Abresham Hakim Arshadwala significantly (p < 0.01) improved the state of markers for cardiac and kidney damage investigated in this model of doxorubicin-induced experimental cardiotoxicity and nephrotoxicity; indicating its potential in limiting doxorubicin toxicity.
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PMID:Protective effects of 'Khamira Abresham Hakim Arshad Wala', a unani formulation against doxorubicin-induced cardiotoxicity and nephrotoxicity. 2106 81

Doxorubicin (DOX) is a potent antitumor agent, but the cardiotoxicity mediated by the formation of reactive oxygen species limit its clinical use. The present study aims to explore electrocardiographic and biochemical evidence for the cardioprotective effect of two antioxidants, Lycium barbarum polysaccharides (LBP, the main antioxidant in Lycium barbarum) and edaravone (a potent free radical scavenger, EDA) against DOX-induced acute cardiotoxicity in beagle dogs. In this study, male beagle dogs received daily treatment of either LBP (20 mg/kg, per os (p.o.)) or EDA (2 mg/kg, intravenously (i.v.)) for 7 d and then followed by an intravenous injection of DOX (1.5 mg/kg). DOX (15 mg/kg) significantly induced acute cardiotoxicity in dogs characterized by conduction abnormalities (including decreased heart rate, ST segment elevation, QT intervals prolongation, inverted T wave, arrhythmia, and myocardial ischemia) and increased serum creatine kinase (CK) and aspartate aminotransferase (AST). Pretreatment with LBP or EDA effectively alleviated both DOX-associated conduction abnormalities and increased serum CK and AST. Moreover, physiological and serum biochemical evidences demonstrated that EDA is more effective than LBP in alleviating these abnormalities produced by DOX in heart. All these results confirm and extend previous observations in rats concerning the effectiveness of LBP or EDA against DOX-induced cardiomyopathy.
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PMID:Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs. 2196 90

Doxorubicin, a very potent and often used anti-cancer drug, is largely limited due to the dose-related toxic effects. The present study investigated whether berberine, a natural product alkaloid, can reduce the liver injury induced by doxorubicin. Mice of either gender were randomly divided into four groups: the control group, doxorubicin group, berberine group, and berberine+doxorubicin group. In the tests, body weight, general condition and mortality of the mice were observed, and serum alanine aminotransferase and aspartate transaminase levels were determined to evaluate liver function. Furthermore, the liver was excised for determination of the weight changes, as well as histopathological analysis in the tissues. Mortality rate and significant decline in body weight, and increased plasma alanine aminotransferase and aspartate transaminase activities were observed in doxorubicin-treated mice. These changes were significantly prevented by pretreatment with berberine. Histopathological studies showed that doxorubicin caused structural injuries, such as vascular congestion, inflammatory cell infiltration, hepatocellular degeneration and necrosis, fibrosis in the liver. These histopathological changes were largely attenuated by berberine pretreatment. These findings indicate that berberine has the hepatoprotective effect on doxorubicin-induced liver injury in mice.
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PMID:Protective effects of berberine on doxorubicin-induced hepatotoxicity in mice. 2268 20

The aim of the study was to evaluate the possibility to reduce the doxorubicin toxic effects by its immobilization with N-stearoylethanolamine (NSE) on nanocarier polyethylene glycol. The studied parameters of the doxorubicin toxicity were: the level of creatinine in the mice blood plasma and activity of alanine aminotransferase and aspartate aminotransferase in the blood plasma of mice. The activity of catalase superoxide dismutase, glutathione peroxidase and intensity of lipid peroxidation was determined in the tissues of the heart, kidneys and liver. Doxorubicin in the content of nanocarrier alone caused an increase of serum creatinine and aspartateaminotrasferase activity in plasma of experimental animals with carcinoma. Nanocomposite which contained doxorubicin and NSE, did not cause an increase of these parameters. It has been shown that the administration of a carrier containing doxorubicin to mice with Lewis lung carcinoma caused the decrease of catalase activity in mice with carcinoma. The combination of NSE and doxorubicin on the carrier led to the normalization of this parameter to the level of intact animals. NSE immobilized on a carrier together with doxorubicin caused a decrease in the activity of superoxide dismutase in the kidney tissue of mice with tumor. The tumor growth caused the increase of the of superoxide dismutase in mice. The administration of a carrier which contained doxorubicin and NSE normalized superoxide dismutase in heart tissue contrary of kidney. The obtained results show the antitoxic and antioxidant effects of N-stearoylethanolamine immobilized in the nanocarrier complex together with doxorubicin.
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PMID:[Antitoxic and antioxidant effects of N-stearoylethanolamin in the content of nanocomposite complex with doxorubicin in organs of mice with Lewis carcinoma]. 2447 27


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