Protective effect of bilberry (Vaccinium myrtillus) against doxorubicin-induced oxidative cardiotoxicity in rats

Abstract

Background: Doxorubicin (DOX) is a commonly used chemotherapeutic agent. It is associated with serious dose-limiting cardiotoxicity, which is at least partly caused by generation of reactive oxygen species (ROS). Supplementations with bilberries were effective in reducing oxidative stress in many tissue injuries due their high content of antioxidants. The present study investigated the potential protective effect of bilberry extract against DOX-induced cardiotoxicity in rats.

Material/methods: Rats were treated orally with a methanolic extract of bilberry for 10 days. DOX was injected intraperitoneally on day 7. Twenty-four hours after the last bilberry administration, rats were subjected to ECG study. Blood was then withdrawn and cardiac tissues were dissected for assessment of oxidative stress and cardiac tissue injury. Cardiac tissues were also subjected to histopathological examination.

Results: Bilberry extract significantly inhibited DOX-provoked reduced glutathione depletion and accumulation of oxidized glutathione, malondialdehyde and protein carbonyls in cardiac tissues. This was accompanied by significant amelioration of reduced cardiac catalase, superoxide dismutase, and glutathione peroxidase activities; and increased cardiac myeloperoxidase activity in response to DOX challenge. Pretreatment with bilberry significantly guarded against DOX-induced increase in serum activities of lactate dehydrogenase, creatine phosphokinase and creatine kinase-MB, as well as the level of troponin I. Bilberry alleviated ECG changes in rats treated with DOX and attenuated its pathological changes.

Conclusions: Bilberry protects against DOX-induced cardiotoxicity in rats. This can be attributed, at least in part, to its antioxidant activity.

Figure 1

The effect of bilberry on doxorubicin (DOX)-induced changes in ECG tracing. Control ECG (A) shows control heart rate, ST segment and interval, and QT interval. Bilberry ECG tracing (B) shows control heart rate, ST segment and interval, and QT interval. DOX-treated group (C) shows bradycardia, depressed long ST segment, and long QT interval. DOX+bilberry group (D) shows nearly normalized heart rate, ST segment and QT interval.

Figure 2

The effect of bilberry on doxorubicin (DOX)-induced alterations in serum biomarkers of cardiac injury; (A) lactate dehydrogenase (LDH), (B) creatine phosphokinase (CPK), (C) creatine phosphokinase isoenzyme MB (CK-MB) and (D) troponin I. Data are the mean ±SEM of 12 rats in DOX group and 8 rats in the other groups. ^ap<0.05 vs. corresponding control group. ^bp<0.05 vs. corresponding DOX group.

Figure 3

The effect of bilberry on doxorubicin (DOX)-induced alterations in the histology of cardiac muscle. Histopathological effects of cardiac tissues from control and bilberry groups show normal histological pattern (A and B, respectively). Cardiac tissues from doxorubicin (DOX)-treated group show severe vacuolar degeneration (VD) and interstitial edema (E) (C). Cardiac tissues from bilberry+DOX treated rats show some congestion (C) and minimal interstitial edema (E) with no fibrosed bands (D) (H & E ×125).