Chemosensetizing and cardioprotective effects of resveratrol in doxorubicin- treated animals

Abstract

BackgroundDoxorubicin (DOX), an anthracycline antibiotic is one of the most effective anticancer drug used in the treatment of variety of cancers .Its use is limited by its cardiotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of DOX and at the same time its protective effect against DOX-induced cardiotoxicity in rats.MethodsEhrlich ascites carcinoma bearing mice were used in this study. Percent survival of tumor bearing mice was used for determination of the Cytotoxic activity of DOX in presence and absence of RSVL. Uptake and cell cycle effect of DOX in tumor cells in the presence of RSVL was also determined. Histopatholgical examination of heart tissues after DOX and/or RSVL therapy was also investigated.ResultsDOX at a dose level of 15 mg/kg increased the mean survival time of tumor bearing mice to 21 days compared with 15 days for non tumor-bearing control mice. Administration of RSVL at a dose level of 10 mg/kg simultaneously with DOX increased the mean survival time to 30 days with 70% survival of the tumor-bearing animals. RSVL increased the intracellular level of DOX and there was a strong correlation between the high cellular level of DOX and its cytotoxic activity. Moreover, RSVL treatment showed 4.8 fold inhibition in proliferation index of cells treated with DOX. Histopathological analysis of rat heart tissue after a single dose of DOX (20 mg/kg) showed myocytolysis with congestion of blood vessels, cytoplasmic vacuolization and fragmentation. Concomitant treatment with RSVL, fragmentation of the muscle fiber revealed normal muscle fiber.ConclusionThis study suggests that RSVL could increase the cytotoxic activity of DOX and at the same time protect against its cardiotoxicity.

Effect of metformin and adriamycin on transplantable tumor model

“…These results were in accordance with El- Dayem et al (2013), Mookerjee et al (2006) and Osman et al (2013). ADR was thought to intercalate into DNA leading to disruption of topoisomerase-II-mediated DNA repair (Thom et al, 2011).…”

The Possible Chemosensitizing Effect of Different Doses of Indol-3-Carbinol on Transplantable Tumor Model Treated with Doxorubicin

“…These results were in agreement with El-Dayem et al [27] and Osman et al [28] who reported that DOX has potent antioxidant and anti-inflammatory properties which, with its effects on apoptosis, may contribute to its anti-tumor properties.…”

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

“…The authors of that study proposed that resveratrol prevents hypertrophy by antagonizing the aryl hydrocarbon receptor (AhR) and inhibiting CYP1A1 enzyme [278], suggesting that resveratrol may also protect against chemotherapy-induced cardiomyopathy through its AhR-antagonistic properties. The translational potential of these findings is very promising, since resveratrol has also been shown to augment the chemotherapeutic activity of several anti-cancer agents including doxorubicin [265,279,280]. Nevertheless, there is very limited information about the cardioprotective effects of resveratrol in cancer patients treated by doxorubicin or other cardiotoxic chemotherapeutic agents.…”

“…doxorubicin, sunitinib, cisplatin, and trastuzumab) have been demonstrated to cause severe acute and chronic cardiotoxic effects that may lead to cardiac dysfunction and heart failure [202,203]. A number of studies have demonstrated that resveratrol protects against doxorubicin-induced cardiotoxicity in a variety of animal models (Table 5) [261][262][263][264][265][266]. Multiple mechanisms have also been proposed to explain the protective effect of resveratrol against doxorubicin-induced cardiotoxicity.…”