Activity of d,l‐α‐Tocopherol (Vitamin E) against Cardiotoxicity Induced by Doxorubicin and Doxorubicin with Cyclophosphamide in Mice

Abstract

The aim of this study was to investigate the cardioprotective activity of vitamin E against doxorubicin alone and doxorubicin in combination with cyclophosphamide in mice. Female BalbC/NIH mice were treated with vitamin E (100 IU/kg, orally) 24 hr before single bolus doses of doxorubicin (10 mg/kg, intravenously), or doxorubicin and cyclophosphamide (150 mg/kg, intraperitoneally). Non-treated animals served as negative controls, while positive control groups received doxorubicin or doxorubicin and cyclophosphamide. For evaluation, serum enzyme activity of aspartate aminotransferase (AST), lactate dehidrogenase (LDH), a-hydroxybutirate dehydrogenase (a-HBDH), and creatine kinase (CK) at 48 hr and histopathology examination of the heart tissue (Billigham rules) at 1.5 and 3 months followed to treatments were used. In sera of mice treated with vitamin E prior to doxorubicin, the creatine kinase and % a-HBDH activity were significantly reduced, compared to positive control. Histopathology changes (scored as 1.5 at 1.5 and 3 months respectively) were not significant compared to negative control at both time points of examination. In animals which received vitamin E before doxorubicin and cyclophosphamide, none of the serum enzymes was significantly reduced compared to positive control, but non-significant increase in AST and creatine kinase activity was detected (3% and 16.57% respectively). The degree of myocardial damage was significantly higher compared to non-treated group (2.0 and 2.5 at 1.5 and 3 months respectively). Current results show that vitamin E in single oral dose failed to inhibit acute cardiotoxic activity of doxorubicin, but suspended further progression of the heart muscle damage over the time. On the contrary, vitamin E did not attain any cardioprotection against doxorubicin and cyclophosphamide in combination.

Mitochondrial pyruvate transport: a historical perspective and future research directions

“…Most of doxorubicin’s deleterious effects on the heart are attributed to reactive oxygen species generation, yet treatment with antioxidants appears to have little effect on the cardiotoxicity [134]. Increased anaerobic glycolysis and lactate formation have been observed in hearts from doxorubicin-treated rats [135], suggesting that there may indeed be a defect in mitochondrial pyruvate import.…”

Ratlarda Deneysel Siklofosfamid Toksikasyonunda Silimarin ve Curcuminin Koruyucu ve Antigenotoksik Etkileri

“…In the present study, SOD enzyme activity levels were found to be significantly lower than those in the control group in the group CP-only group, which suggests that CP may markedly induce superoxide anion radical formation [5] . In the present study, SOD enzyme activity levels in the groups in which SLY and CUR were administered concurrently with CP, were found to be significantly different from those in the CP-only group, suggesting that both SLY and CUR influence the antioxidant system via SOD in the liver and kidneys, as in other chemical agents reported in the literature [4,8] .…”

“…Despite its therapeutic importance, a wide range of adverse effects, including nephrotoxicity [2] , hepatotoxicity [3] , cardiotoxicity [4] and male reproductive toxicity [5] , have been reported for the drug.…”

Cancer treatment-related cardiac toxicity: prevention, assessment and management

“…A study in female BalbC/NIH mice treated with vitamin E at 24 h before bolus doses of doxorubicin or doxorubicin and cyclophosphamide (intraperitoneal) assessed cardiac biopsy and blood markers at 1.5 and 3 months after treatment [50]. It was concluded from the study that vitamin E failed to prevent the occurrence of anthracycline-induced cardiotoxicity, though it might have mitigated late progression of cardiac damage at least in the doxorubicin only group.…”

“…It was concluded from the study that vitamin E failed to prevent the occurrence of anthracycline-induced cardiotoxicity, though it might have mitigated late progression of cardiac damage at least in the doxorubicin only group. A human pilot study of 13 chemotherapy patients failed to detect a difference between patients treated with vitamin E and patients treated without vitamin E [50][51][52].…”