Folic acid ameliorates celecoxib cardiotoxicity in a doxorubicin heart failure rat model

Abstract

Context: The cardiotoxic effect of selective cyclo-oxygenase-2 inhibitors is well known. While rofecoxib and valdecoxib have been withdrawn, celecoxib remains on the market. Folic acid, a naturally occurring vitamin, has been shown to reduce myocardial ischemia and post-reperfusion injury in rats.

Objective: This study examined the cardiac effects of celecoxib and folic acid on doxorubicin-induced cardiomyopathy in rats.

Materials and methods: Cardiomyopathy was induced in male Wistar rats with six intraperitoneal injections of 2.5 mg/kg doxorubicin over a period of two weeks. The effect of 28 days of celecoxib (100 mg/kg/day) and its combination with folic acid (10 mg/kg/day) was studied on doxorubicin-induced cardiomyopathy according to serum lactate dehydrogenase (LDH), creatine kinase (CK-MB), troponin-T (Tn-T), tumor necrosis factor alpha (TNF-α), cardiac thiobarbituric acid reactive substance (TBARS), and glutathione (GSH) levels as well as systolic blood pressure (SBP), heart rate (HR) and ultrastructural studies.

Results: Celecoxib cardiotoxicity was manifested by significant increases in the LDH, Tn-T, TNF-α, CK-MB, SBP, HR (p < 0.001) and TBARS (p < 0.01) levels and a significant decrease in the GSH (p < 0.05) level when used alone or administered with doxorubicin. However, the combination of folic acid with celecoxib caused a significant reversal of these parameters and reduced the cardiotoxicity of celecoxib that was aggravated by doxorubicin. The ultrastructural study also revealed myocardial protection with this combination.

Discussion and conclusion: Folic acid protects against the cardiotoxic effects of celecoxib, which are aggravated in the presence of doxorubicin. Folic acid may act as a useful adjunct in patients who are taking celecoxib.

KEYWORDS:

• Selective COX-2 inhibitor
• cardiovascular
• Tn-T
• TNF-α

Acknowledgments

The authors thank Dr. R M Pandey, Professor and Head, Department of Biostatistics, All India Institute of Medical Science, and his associates, Mr. Vineet Kumar and Mr. Ashish Upadhyay, for their kind help with statistics.

Disclosure statement

The authors have no conflicts of interest to report.

Funding

This work was supported by the University Grants Commission, New Delhi, under Grant [F7-268/2009 (BSR)].

Geolocation information

The study was carried out at Jamia Hamdard, Hamdard University, New Delhi.

The geolocation of the study area is 28.5154° latitude and 77.2521° longitude.

Additional information

Funding

This work was supported by the University Grants Commission, New Delhi, under Grant [F7-268/2009 (BSR)].