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Caspase-3 levels (CASP-3) in Doxorubicin Induced-Cardiotoxicity: Role of Metformin Pretreatment

Hayder M Al-Kuraishy and Reem Ghanim Hussein

Background: The greatest danger of doxorubicin-induced toxicity is cardiotoxicity hence; administration of doxorubicin should be dose-limited. There are several biomarkers used to detect the cardiotoxicity which are cardiac troponin and caspase-3.

Aim: The aim of present study was assess caspase-3 serum levels in acute doxorubicin induced-cardiotoxicity in rats regarding the protective role of metformin.

Materials and methods: 18 Male Sprague Dawley rat were used in this experimental study. The rats were divided into three groups these were: Group І: Six rats as control group received normal saline 5 ml/kg/day intra-peritoneal for ten days. Group ІІ: Six rats treated with normal saline 5 ml/kg/day intra-peritoneal for ten days and doxorubicin 20 mg/kg was given as a single dose intra-peritoneal at 8th day. Group ІІІ: Six rats treated with metformin 50 mg/kg/day orally via gavage for 10 days and doxorubicin 20 mg/kg was given as a single dose intra-peritoneal at 8th day. cTn-I serum level and caspase-3 serum level were assessed by specific ELISA kit method.

Results: Doxorubicin increase caspase-3 and cardiac Troponin I levels significantly p<0.01 compared to the control. Pre-treatment with metformin led to significant reduction in cTnI and caspase-3 serum levels compare to doxorubicin group p<0.05.

Conclusion: In doxorubicin induced-cardiotoxicity, caspase-3 is increased and regarded as a surrogate biomarker and pre-treatment with metformin produced significant cardio-protection in rats through reduction of caspase-3 serum levels.