Cranberry (Vaccinium macrocarpon) protects against doxorubicin-induced cardiotoxicity in rats.
Doxorubicin (DOX) is a widely used cancer chemotherapeutic agent. However, it generates free oxygen radicals that result in serious dose-limiting cardiotoxicity. Supplementations with berries were proven effective in reducing oxidative stress associated with several ailments. The aim of the current study was to investigate the potential protective effect of cranberry extract (CRAN) against DOX-induced cardiotoxicity in rats. CRAN was given orally to rats (100mg/kg/day for 10 consecutive days) and DOX (15mg/kg; i.p.) was administered on the seventh day. CRAN protected against DOX-induced increased mortality and ECG changes. It significantly inhibited DOX-provoked glutathione (GSH) depletion and accumulation of oxidized glutathione (GSSG), malondialdehyde (MDA), and protein carbonyls in cardiac tissues. The reductions of cardiac activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were significantly mitigated. Elevation of cardiac myeloperoxidase (MPO) activity in response to DOX treatment was significantly hampered. Pretreatment of CRAN significantly guarded against DOX-induced rise of serum lactate dehydrogenase (LDH), creatine phosphokinase (CK), creatine kinase-MB (CK-MB) as well as troponin I level. CRAN alleviated histopathological changes in rats' hearts treated with DOX. In conclusion, CRAN protects against DOX-induced cardiotoxicity in rats. This can be attributed, at least in part, to CRAN's antioxidant activity.
Elberry AA
，Abdel-Naim AB
，Abdel-Sattar EA
，Nagy AA
，Mosli HA
，Mohamadin AM
，Ashour OM
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Nitric oxide and oxidative stress in brain and heart of normal rats treated with doxorubicin: role of aminoguanidine.
Doxorubicin (DOX) is a potent antitumor antibiotic drug known to cause severe cardiac toxicity. Moreover, its adverse effects were found to be extended to the cerebral tissue. Several mechanisms for this toxicity have been ascribed. Currently, one of the most accepted mechanisms is through free radicals; however, the exact role of nitric oxide (NO) is still unclear. Accordingly, a NO-synthase inhibitor with some antioxidant property, aminoguanidine (AG), was selected to examine its potential protective effect against DOX-induced toxicity. Male Wistar albino rats (150-200 g) were allocated into a normal control group, DOX-induced toxicity group, and DOX + AG-treated group. DOX was injected i.p. at a dose of 10 mg/kg divided into four equal injections over a period of 2 weeks. AG was injected i.p. at a dose of 100 mg/kg 1 h before each DOX injection. The animals were sacrificed 24 h after the last DOX injection and the following parameters were measured: serum lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activities, cardiac and cerebral contents of malondialdehyde (MDA), conjugated diene (CD), glutathione (GSH), NO, and cytosolic calcium, as well as superoxide dismutase (SOD) and glutathione peroxidase (GSHP(X)) activities. Cardiotoxicity was manifested by a marked increase in serum LDH and CPK in addition to the sharp increase in MDA reaching eightfolds the basal level. This was accompanied by significant increase in CD, NO, cytosolic calcium, SOD, and GSHP(X) content/activity by 69, 85, 76, 125, and 41% respectively as compared to normal control. On the other hand, GSH was significantly depressed. In brain, only significant increase in MDA and GSHP(X) and decrease in GSH were obtained but to a lesser extent than the cardiac tissue. AG treatment failed to prevent the excessive release of cardiac enzymes; however, it alleviated the adverse effects of DOX in heart. AG administration resulted in marked decrease in the elevated levels of MDA, NO, SOD, and GSHP(X), however, MDA level was still pathological. The altered parameters in brain were restored by AG. It is concluded that, AG could not provide complete protection against DOX-induced toxicity. Therefore, it is recommended that, maintenance of the endogenous antioxidant, GSH, and regulation of calcium homeostasis must be considered, rather than NO formation, to guard against DOX-induced toxicity.
Abd El-Gawad HM
，El-Sawalhi MM
《JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY》
Cardioprotective effect of HPLC standardized ethanolic extract of Terminalia pallida fruits against isoproterenol-induced myocardial infarction in albino rats.
Terminalia pallida is an evergreen endemic tree, mentioned in Ayurveda as the fruits of Terminalia pallida are excellent in cardioprotective property. Tribal people use Terminalia pallida fruit for the treatment of diabetes and this plant widely used in many other disorders.
The present investigation was to evaluate the antioxidant, biochemical profile and histological studies of qualitatively standardized ethanolic extract of Terminalia pallida fruits (TpFE) against isoproterenol-induced myocardial infarction in rats.
TpFE was standardized by high performance liquid chromatography (HPLC) and mass spectroscopy (MS). Rats were pretreated orally with different doses of TpFE (100, 300, and 500mgkg(-1) body weight) and cardioprotective positive control gallic acid (GA) for 30 days prior to isoproterenol (ISO) induced myocardial infarction. The rats were sacrificed, hearts were collected and homogenized for biochemical analysis. The effects on total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), lipid peroxidation (LPO) marker, malondialdehyde (MDA), creatine kinase (CK), lactate dehydrogenase (LDH), alanine transaminase (ALT), aspartate transaminase (AST), catalase (CAT), glutathione peroxidase (GPx), sodium potassium (Na(+)/K(+)), calcium (Ca(2+)) and magnesium (Mg(2+)) adenosine triphosphatases (ATPases) were estimated in heart tissue homogenate.
Rats administered with ISO showed a significant increase in TC, TG, LDL-C, VLDL-C, and MDA and a significant decrease in HDL-C, cardiac marker enzymes - CK, LDH, ALT and AST. ISO significantly reduced antioxidants - CAT, GPx, and membrane bound enzymes - Na(+)/K(+), Ca(2+) and Mg(2+) ATPases. Pretreatment with TpFE (100, 300, and 500mgkg(-1) bw) and GA (15mgkg(-1) bw) for a period of 30 days significantly inhibited the effects of ISO. Moreover, biochemical findings were supported by histopathological observations.
The present study provide evidence for the first time, that TpFE pretreatment ameliorated myocardial injury in ISO-induced myocardial infarcted rats and exhibited cardioprotective activity.
Shaik AH
，Rasool SN
，Vikram Kumar Reddy A
，Abdul Kareem M
，Saayi Krushna G
，Lakshmi Devi K
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