Hesperidin ameliorates cisplatin induced hepatotoxicity and attenuates oxidative damage,cell apoptosis,and inflammation in rats

Cisplatin is one of the most widely used chemotherapeutic anti-cancer drugs that is associated with multiple systemic toxicities limiting its use. The present study aimed to evaluate the hepato-protective effect of hesperidin against cisplatin-induced toxicity. Thirty-two adult male albino rats were equally split into four groups, the first group served as control received normal saline, the second group (CIS) received a single intraperitoneal dose of cisplatin (7.5 mg/kg bw) on the 22nd day of the experiment, the third group (HES) treated once daily with hesperidin (200 mg/kg bw, orally) for 21 days, and the last group (HES + CIS) pretreated once daily with hesperidin followed by a single intraperitoneal dose of cisplatin. Twenty-four hours later, samples were collected for further investigations. CIS-intoxication resulted in a significant decrease in the erythrogram along with thrombocytopenia leukopenia, and lymphopenia. Furthermore, CIS administration significantly elevated serum activity of liver enzymes, total, and indirect bilirubin as well serum glucose, total cholesterol, and triglycerides levels, meanwhile serum total protein, and globulin levels were significantly reduced. The hepatic MDA was markedly elevated with a concomitant decline in the hepatic antioxidant enzymes and severe alterations in the hepatic tissue architecture in CIS-intoxicated rats. Additionally, CIS-induced overexpression of hepatic Bax, caspase-3, and TNF-α, with no effect on hepatic expression of IL-10. Interestingly, HES pretreatment improved the CIS-induced hemato-biochemical, molecular and histopathological alterations. In conclusion, hesperidin hepato-protective effects against CIS might be mediated by its antioxidant, anti-inflammatory, and anti-apoptotic properties.     

Effect of ursolic acid treatment on apoptosis and DNA damage in isoproterenol-induced myocardial infarction

The present study was designed to evaluate the protective effect of ursolic acid (UA) against isoproterenol-induced myocardial infarction. Myocardial infarction was induced by subcutaneous injection of isoproterenol hydrochloride (ISO) (85 mg/kg BW), for two consecutive days. ISO-induced rats showed elevated levels of cardiac troponins T (cTn T) and I (cTn I) and increased activity of creatine kinase-MB (CK-MB) in serum. Lipid peroxidative markers (thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (HP)) elevated in the plasma and heart tissue whereas decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)) in erythrocytes and heart tissue of ISO-induced rats. Non-enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione (GSH)) levels were decreased significantly in the plasma and heart tissue of ISO-induced rats. Furthermore, ISO-induced rats showed increased DNA fragmentation, upregulations of myocardial pro-apoptotic B-cell lymphoma-2 associated-x (Bax), caspase-3, -8 and -9, cytochrome c, tumor necrosis factor-α (TNF-α), Fas and down-regulated expressions of anti-apoptotic B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL). UA-administered rats showed decreased levels/activity of cardiac markers, DNA fragmentation and the levels of lipid peroxidative markers in the plasma and heart tissue. Activities of enzymatic antioxidants were increased significantly in the erythrocytes and heart tissue and also non-enzymatic antioxidants levels were increased significantly in the plasma and heart tissue in UA-administered rats. UA influenced decreased DNA fragmentation and an apoptosis by upregulation of anti-apoptotic proteins such as Bcl-2, Bcl-xL and down-regulation of Bax, caspase-3, -8 and -9, cytochrome c, TNF-α, Fas through mitochondrial pathway. Histopathological observations were also found in line with biochemical parameters. Thus, results of the present study demonstrated that the UA has anti-apoptotic properties in ISO-induced rats.     

Berbamine ameliorates isoproterenol-induced myocardial infarction by inhibiting mitochondrial dysfunction and apoptosis in rats

Berbamine (BBM), a bisbenzylisoquinoline alkaloid from roots, bark, and stem of Berberis plant such as Berberis aristata has a wide range of pharmacological activities. However, the evidence for the cardioprotective effect of BBM is inadequate and the molecular mechanism of BBM remains unclear. This study investigated the underlying molecular mechanism of BBM-mediated cardioprotection on isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. The assays of mitochondria antioxidant status, mitochondrial marker enzymes, and electron microscopic analysis of mitochondria revealed BBM significantly prevented the mitochondrial dysfunction induced by ISO. The ISO-induced elevation of mitochondrial oxidative stress was also curbed by BBM. Furthermore, pretreatment with BBM protected the heart tissue from ISO-induced apoptosis as evident from decreased terminal dUTP nickend-labeling positive cells and decreased expression of Bax, cytochrome c, cleaved caspase-9, and caspase-3, and poly (ADP-ribose) polymerase and increased expression of Bcl-2 in ISO-induced rats. These current findings suggest that BBM exerts a significant cardioprotective effect on ISO-induced myocardial infarction in rats.     

Serum prolactin levels in rats following isoproterenol-induced myocardial infarction.

Circulating prolactin levels were monitored in nonarteriosclerotic, arteriosclerotic, and hormonally sterilized male and female Sprague-Dawley rats during the acute necrosis and repair phases of myocardial infarction induced by isoproterenol. Male rats are particularly prone to succumb to acute myocardial ischemia but reduction of androgen levels by neonatal sterilization improved survival considerably. Circulating prolactin levels are greatly increased, particularly in females, during acute myocardial ischemia. Since androgens suppress the hypothalamic center for prolactin release, prolactin levels were delayed and transitory in males. It is suggested that the superior survival of female rats may be related to their greater production of prolactin during acute stages of myocardial ischemia, which would dampen the tachycardia-inducing effects of the potent beta-adrenergic stimulating agent, isoproterenol.     

Apocynin attenuates isoproterenol-induced myocardial injury and fibrogenesis

Oxidative stress is mechanistically implicated in the pathogenesis of myocardial injury and the subsequent fibrogenic tissue remodeling. Therapies targeting oxidative stress in the process of myocardial fibrogenesis are still lacking and thus remain as an active research area in myocardial injury management. The current study evaluated the effects of a NADPH oxidase inhibitor, apocynin, on the production of reactive oxygen species and the development of myocardial fibrogenesis in isoproterenol (ISO)-induced myocardial injury mouse model. The results revealed a remarkable effect of apocynin on attenuating the development of myocardial necrotic lesions, inflammation and fibrogenesis. Additionally, the protective effects of apocynin against myocardial injuries were associated with suppressed expression of an array of genes implicated in inflammatory and fibrogenic responses. Our study thus provided for the first time the histopathological and molecular evidence supporting the therapeutic value of apocynin against the development of myocardial injuries, in particular, myocardial fibrogenesis, which will benefit the mechanism-based drug development targeting oxidative stress in preventing and/or treating related myocardial disorders.     

Carnosic acid promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress and apoptosis in mice

Carnosic acid is a well-known antioxidant. Recently, it has been identified as modulator of nuclear factor erythroid 2-related factor 2 (Nrf2). The effect of carnosic acid in the context of cardiovascular disorders has not been studied. In the present study, we investigated the beneficial effect and the underlying cardioprotective mechanism of carnosic acid by using mouse model of isoproterenol (ISO)-induced myocardial stress. Elevated serum levels of Troponin I, CK-MB, LDH, SGOT and SGPT, and myofibrillar degeneration with necrotic damage, and the presence of epicardial inflammatory infiltrate (H & E staining) confirmed the ISO-induced myocardial stress. Myocardial content of vitamin C, reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, NAD(P)H: quinine oxidoreductase 1, superoxide dismutase, catalase, nuclear translocation of Nrf2 and protein expression heme oxygenase-1 were evaluated. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and myocardial expression of cleaved caspase-3, caspase-9, p53, Bax, and Bcl-2 were investigated to assess the apoptotic cell death. Pretreatment with carnosic acid attenuated ISO-induced elevated serum levels of Troponin I, CK-MB, LDH, SGOT and SGPT, and histopathological alterations in heart. Moreover, carnosic acid enhanced the nuclear translocation of Nrf2 and up-regulated the phase II/antioxidant enzyme activities. Furthermore, TUNEL assay and apoptosis-related protein analysis indicated that carnosic acid prevented ISO-induced cardiomyocyte apoptosis. Isoproterenol-induced myocardial lipid peroxidation and protein oxidation were also significantly decreased by carnosic acid pretreatment. The overall results clearly indicate that therapeutic application of carnosic acid might be beneficial in treating cardiovascular disorders.     

Influence of isoproterenol-induced myocardial infarction on certain glycohydrolases and cathepsins in rats

The changes in the activities of certain lysosomal hydrolases, viz., beta-glucuronidase, beta-N-acetylglucosaminidase, beta-galactosidase, beta-glucosidase, alpha-glucosidase, alpha-galactosidase, alpha-mannosidase, cathepsin B, cathepsin D, and collagenolytic cathepsin, in serum and heart of rats subject to myocardial infarction with isoproterenol, were studied during the periods of peak infarction and recovery. The activities of all the enzymes assayed exhibited a significant increase both in serum and in heart at peak infarction stage and these levels returned to normal during the stage of recovery and repair. The infiltration of inflammatory cells at the infarct regions and the altered lysosomal fragility are probably responsible for the increased activity of the enzymes studied. This may also bring about the catabolism of connective tissue constituents as reported in literature.     

间歇运动对心梗大鼠心肌氧化应激和炎症的影响及其机制

目的:探讨间歇运动激活心肌梗死(MI)大鼠SIRT1-Nox4-ROS通路抑制心脏氧化应激和炎症的作用.方法:选取雄性SD大鼠30只,随机分为假手术对照(C)组,心肌梗死(MI)组和心梗+间歇运动(ME)组,每组10只.MI组采用心脏左冠状动脉前降支(LAD)结扎法,建立MI模型.C组大鼠实施假手术,ME组大鼠在MI手...     

Nerolidol,a sesquiterpene,attenuates oxidative stress and inflammation in acetic acid-induced colitis in rats

Targeting oxidative stress and inflammation by novel dietary compounds of natural origin convincingly appears to be one of the most important therapeutic strategies to keep inflammatory bowel diseases (IBD) such as ulcerative colitis disease in remission. It is imperative to investigate naturally occuring plant-derived dietary phytochemicals that are receiving attention for their therapeutic benefits to overcome the debilitating conditions of IBD. In the present study, the effect of nerolidol (NRD), a monocyclic sesquiterpene found in German Chamomile tea, was investigated in acetic acid-induced colitis model in Wistar rats. NRD was orally administered at a dose of 50 mg/kg/day either for 3 days before or 30 min after induction of IBD for 7 days, after intrarectal administration of acetic acid. The body weight, macroscopic, and microscopic analyses of the colon in different experimental groups were observed on days 0, 2, 4, and 7. Acetic acid caused significant reduction in body weight and induced macroscopic and microscopic ulcer along with a significant decline of antioxidants, concomitant to increased malondialdehyde (MDA), a marker of lipid peroxidation, and myeloperoxidase (MPO) activity, a marker of neutrophil activation. Treatment with NRD significantly improved IBD-induced reduction in body weight, improved histology, inhibited MDA formation, and restored antioxidants along with reduced MPO activity. Acetic acid also induced the release of pro-inflammatory cytokines and increased calprotectin, released by neutrophils under inflammatory conditions. NRD treatment significantly reduced calprotectin and pro-inflammatory cytokines. NRD treatment showed potential to improve disease activity and inhibit oxidative stress, lipid peroxidation, and inflammation along with histological preservation of the colon tissues.

     

Preventive effect of rutin on lipids, lipoproteins, and ATPases in normal and isoproterenol-induced myocardial infarction in rats

The present study was designed to evaluate the preventive role of rutin on lipids, lipoproteins, and ATPases in normal and isoproterenol (ISO)-induced myocardial infarction in rats. Rutin (40 and 80 mg/kg) was orally administered to rats for a period of 42 days. After that period, isoproterenol (150 mg/kg) was injected subcutaneously to male wistar rats at an interval of 24 h for 2 days. The weight of heart and the concentrations of total cholesterol, triglycerides, and free fatty acids were increased significantly (p < 0.05), and the concentration of phospholipids was decreased significantly (p < 0.05) in the heart of ISO-treated rats. ISO-treated rats also showed a significant increase (p < 0.05) in the levels of total cholesterol, triglycerides, phospholipids, low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C) with a significant decrease (p < 0.05) in high-density lipoprotein cholesterol (HDL-C) level in serum. The activities of sodium potassium dependent adenosine triphosphatase (Na(+)/K(+) ATPase) and magnesium-dependent adenosine triphosphatase (Mg(2+) ATPase) were decreased significantly (p < 0.05), and the activity of calcium-dependent adenosine triphosphatase (Ca(2+)ATPase) was increased significantly (p < 0.05) in the heart in ISO-treated rats. Pretreatment with rutin at doses of 40 or 80 mg/kg to ISO-treated rats showed a significant (p < 0.05) effect in all the parameters studied. Oral administration of rutin to normal rats did not show any significant effect. Thus, the results of our study show that pretreatment with rutin maintained the levels of lipids, lipoproteins, and ATPases in ISO-induced myocardial infarcted rats. The observed effects might be due to the antioxidant potential of rutin.     

Isocyanates induces DNA damage,apoptosis, oxidative stress,and inflammation in cultured human lymphocytes

Isocyanates, a group of low molecular weight aromatic and aliphatic compounds containing the isocyanate group (?NCO), are important raw materials with diverse industrial applications; however, pathophysiological implications resulting from occupational and accidental exposures of these compounds are hitherto unknown. Although preliminary evidence available in the literature suggests that isocyanates and their derivatives may have deleterious health effects including immunotoxicity, but molecular mechanisms underlying such an effect have never been addressed. The present study was carried out to assess the immunotoxic response of methyl isocyanate (MIC) on cultured human lymphocytes isolated from healthy human volunteers. Studies were conducted to evaluate both dose‐dependent and time‐course response (n = 3), using N‐succinimidyl N‐methylcarbamate, a surrogate chemical substitute to MIC. Evaluation of DNA damage by ataxia telangiectasia mutated (ATM) and γ H2AX protein phosphorylation states; measure of apoptotic index through annexin‐V/PI assay, apoptotic DNA ladder assay, and mitochondrial depolarization; induction of oxidative stress by CM‐H2DCFDA and formation of 8‐hydroxy‐2′ deoxy guanosine; levels of antioxidant defense system enzyme glutathione reductase; and multiplex cytometric bead array analysis to quantify the secreted levels of inflammatory cytokines, interleukin‐8, interleukin‐1β, interleukin‐6, interleukin‐10, tumor necrosis factor, and interleukin‐12p70 parameters were carried out. The results of the study showed a dose‐ and time‐dependent response, providing evidence to hitherto unknown molecular mechanisms of immunotoxic consequences of isocyanate exposure at a genomic level. We anticipate these data along with other studies reported in the literature would help to design better approaches in risk assessment of occupational and accidental exposure to isocyanates. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:429–440, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20260     

Ultrastructure of isoproterenol-induced myocardial damage in chick embryos

Isoproterenol is known to cause severe myocardial lesions when given in toxic doses to adult homoiotherms. Previous studies on chick embryos revealed myocardial damage with scattered necroses in the outer layer of ventricular myocardium. The present ultrastructural study, performed on embryos 6 to 20 days old, has shown various types of cellular lesions; mainly cellular oedema, mitochondrial swelling, necroses of isolated cardiac muscle cells, fatty degeneration, accumulation of glycogen, and signs of increased proteosynthesis in the surviving muscle cells. Morphological features of the lesions differed from those which are known to be induced by isoproterenol in adult animals and seemed to depend on the stage of embryonic development.     

Ethanolic Zingiber officinale R. extract pretreatment alleviates isoproterenol-induced oxidative myocardial necrosis in rats

Ethanolic Z. officinale (ZO) extract (200 mg/kg) pretreatment for 20 days in isoproterenol (ISO)-treated rats significantly increased the levels of endogenous myocardial antioxidants (catalase, superoxide dismutase and tissue glutathione), decreased the levels of serum marker enzymes (lactate dehydrogenase, creatine kinase, aspartate transaminase and alanine transaminase) and increased myocardial lipid peroxides. Histological examination of rat's heart section confirmed myocardial injury with ISO administration and near normal pattern with ethanolic ZO extract pretreatment. The results of the present study, for the first time, provide clear evidence that the ethanolic ZO extract pretreatment enhances the antioxidant defense against ISO-induced oxidative myocardial injury in rats and exhibit cardioprotective property.     

Inhibition of NADPH oxidase by apocynin promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress in rats

Preventive and/or therapeutic interventions for ischemic heart disease have gained considerable attention worldwide. We investigated the mechanism(s) underlying cardioprotection of apocynin (APO) and whether it attenuates isoproterenol (ISO)-induced myocardial damage in vivo. Thirty-two male Wistar Albino rats were randomised into four groups (n?=?8 for each group): Group I (Control); Group II (ISO), ISO was given intraperitoneally (ip) (150?mg/kg/d) daily for 2 consecutive days; Group III (APO?+?ISO), APO was applied ip 20?mg/kg 30?min before the first ISO administration and continued for the next 2 d after the second ISO administration; Group IV (ISO?+?APO), after the ISO treatment on days 1 and 2, 20?mg/kg APO was given ip on days 3 and 4. Cardioprotective effects of APO were evaluated by biochemical values, histopathological observations and the antiapoptotic relative proteins. Mean blood pressure, heart rate, and electrocardiography (ECG) were also monitored. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), caspase-3 and connexin 43 levels were determined. Major ECG changes were observed in the ISO-treated rats. MDA, TOS, OSI and creatine kinase levels decreased and SOD, CAT, GSH and TAC levels increased, indicating that APO reduced cardiac injury and oxidative stress compared with controls. APO also decreased the number of cardiomyocytes with pyknotic nuclei, inflammatory cell infiltration, intracytoplasmic vacuolisation and myofibrils. APO provides preventive and therapeutic effects on ISO-induced myocardial injury in rats by inhibiting reactive oxygen species production, blocking inflammation and enhancing antioxidant status.     

Adrenomedullin gene delivery attenuates myocardial infarction and apoptosis after ischemia and reperfusion

Adrenomedullin (AM) has been shown to protect against cardiac remodeling. In this study, we investigated the potential role of AM in myocardial ischemia-reperfusion (I/R) injury through adenovirus-mediated gene delivery. One week after AM gene delivery, rats were subjected to 30-min coronary occlusion, followed by 2-h reperfusion. AM gene transfer significantly reduced the ratio of infarct size to ischemic area at risk and the occurrence of sustained ventricular fibrillation compared with control rats. AM gene delivery also attenuated apoptosis, assessed by both terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and DNA laddering. The effect of AM gene transfer on infarct size, arrhythmia, and apoptosis was abolished by an AM antagonist, calcitonin gene-related peptide [CGRP(8-37)]. Expression of human AM significantly increased cardiac cGMP levels and reduced superoxide production, superoxide density, NAD(P)H oxidase activity, p38 MAPK activation, and Bax levels. Moreover, AM increased Akt and Bad phosphorylation and Bcl-2 levels, but decreased caspase-3 activation. These results indicate that AM protects against myocardial infarction, arrhythmia, and apoptosis in I/R injury via suppression of oxidative stress-induced Bax and p38 MAPK phosphorylation and activation of the Akt-Bad-Bcl-2 signaling pathway. Successful application of this technology may have a protective effect in coronary artery diseases.     

Antilipoperoxidative and antioxidant effects of S-allyl cysteine sulfoxide on isoproterenol-induced myocardial infarction in Wistar rats

Our study evaluates the preventive effect of S-allyl cysteine sulfoxide (SACS) on lipid peroxidative products and enzymic and nonenzymic antioxidants in isoproterenol (ISO) induced myocardial infarction in rats. The male Wistar rats were rendered myocardial infarction by ISO (150 mg kg(-1), once a day for two days). The concentrations of thiobarbituric acid reactive substances and lipid hydroperoxides were increased in hearts from ISO-treated rats, whereas the content of enzymic and nonenzymic antioxidants were declined in rats administered ISO. Oral pretreatment with SACS (40 mg kg(-1) and 80 mg kg(-1) daily for a period of 35 days) significantly (p < 0.05) decreased the lipid peroxidative products and significantly (p < 0.05) increased antioxidants in ISO-induced rats. Oral administration of SACS (40 mg kg(-1) and 80 mg kg(-1)) did not show any significant effect in normal rats. Thus, the present study shows that SACS exhibits antilipoperoxidative and antioxidant effects in experimental myocardial infarction.     

Nootkatone confers hepatoprotective and anti‐fibrotic actions in a murine model of liver fibrosis by suppressing oxidative stress,inflammation, and apoptosis

In this study, the hepatoprotective and anti‐fibrotic actions of nootkatone (NTK) were investigated using carbon tetrachloride (CCl₄)‐induced liver fibrosis in mice. CCl₄ administration elevated serum aspartate and alanine transaminases levels, respectively. In addition, CCl₄ produced hepatic oxidative and nitrative stress, characterized by diminished hemeoxygenase‐1 expression, antioxidant defenses, and accumulation of 4‐hydroxynonenal and 3‐nitrotyrosine. Furthermore, CCl₄ administration evoked profound expression of pro‐inflammatory cytokine expressions such as tumor necrosis factor‐α, monocyte chemoattractant protein‐1, and interleukin‐1β in hepatic tissues, which corroborated with nuclear factor κB activation. Additionally, CCl₄‐treated animals exhibited higher apoptosis, characterized by increased caspase 3 activity, DNA fragmentation, and poly (ADP‐ribose) polymerase activation. Moreover, histological and biochemical investigations revealed marked fibrosis in the livers of CCl₄‐administered animals. However, NTK treatment mitigated CCl₄‐induced phenotypic changes. In conclusion, our findings suggest that NTK exerts hepatoprotective and anti‐fibrotic actions by suppressing oxidative stress, inflammation, and apoptosis.     

Effect of Inula racemosa root extract on cardiac function and oxidative stress against isoproterenol-induced myocardial infarction

The cardioprotective potential of Inula racemosa root hydroalcoholic extract against isoproterenol-induced myocardial infarction was investigated in rats. The rats treated with isoproterenol (85 mg/kg, s.c.) exhibited myocardial infarction, as evidenced by significant (P < 0.05) decrease in mean arterial pressure, heart rate, contractility, relaxation along with increased left ventricular end diastolic pressure, as well as decreased endogenous myocardial enzymatic and non-enzymatic antioxidants. Isoproterenol also significantly (P < 0.05) induced lipid peroxidation and increased leakage of myocyte injury marker enzymes. Pretreatment with I. racemosa extract (50, 100 or 200 mg/kg per day, p.o.) for 21 consecutive days, followed by isoproterenol injections on days 19th and 20th significantly (P < 0.05) improved cardiac function by increasing the heart rate, mean arterial pressure, contractility and relaxation along with decreasing left ventricular end diastolic pressure. Pretreatment with I. racemosa also significantly (P < 0.05) restored the reduced form of glutathione and endogenous antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase from the heart, which were depleted after isoproterenol administration. In addition to restoration of antioxidants, I. racemosa significantly (P < 0.05) inhibited lipid peroxidation and prevented the leakage of myocytes specific marker enzymes creatine phosphokinase-MB and lactate dehydrogenase from the heart. Thus, it is concluded that I. racemosa protects heart from isoproterenol-induced myocardial injury by reducing oxidative stress and modulating hemodynamic and ventricular functions of the heart. Present study findings demonstrate the cardioprotective effect of I. racemosa and support the pharmacological relevance of its use and cardioprotection mechanism in ischemic heart disease as well as substantiate its traditional claim.     

Curcumin ameliorates doxorubicin‐induced cardiotoxicity by abrogation of inflammation,apoptosis, oxidative DNA damage,and protein oxidation in rats

Doxorubicin (DXR) is a highly effective drug for chemotherapy. However, cardiotoxicity reduces its clinical utility in humans. The present study aimed to assess the ameliorative effect of curcumin against DXR‐induced cardiotoxicity in rats. Rats were subjected to oral treatment of curcumin (100 and 200 mg/kg body weight) for 7 days. Cardiotoxicity was induced by single intraperitoneal injection of DXR (40 mg/kg body weight) on the 5th day and the rats sacrificed on 8th day. Curcumin ameliorated DXR‐induced lipid peroxidation, glutathione depletion, decrease in antioxidant (superoxide dismutase, catalase, and glutathione peroxidase) enzyme activities, and cardiac toxicity markers (CK‐MB, LDH, and cTn‐I). Curcumin also attenuated activities of Caspase‐3, cyclooxygenase‐2, inducible nitric oxide synthase, and levels of nuclear factor kappa‐B, tumor necrosis factor‐α, and interleukin‐1β, and cardiac tissue damages that were induced by DXR. Moreover, curcumin decreased the expression of 8‐OHdG and 3,3′‐dityrosine. This study demonstrated that curcumin has a multi‐cardioprotective effect due to its antioxidant, anti‐inflammatory, and antiapoptotic properties.