www.ijbcp.com International Journal of Basic & Clinical Pharmacology | May 2017 | Vol 6 | Issue 5 Page 1054
IJBCP International Journal of Basic & Clinical Pharmacology
Print ISSN: 2319-2003 | Online ISSN: 2279-0780
Original Research Article
Effect of metformin on ECG, HR and BP of rats administered with
cardiotoxic agent doxorubicin
Promise Madu Emeka*, Anas Al-Ahmed
INTRODUCTION
Cardiovascular complications in the use of drugs are
some of adverse effects defying management solution,
particularly for those agents whose benefit to risk ratio is
on the border line. This worrying phenomenon, has led to
the use of multiple regimen to mitigate the likely events
of toxicity. Patients who are on certain medications used
in the treatment of disease like cancer and psychotics
illness do have the added complications of increased risk
of cardiovascular complications. This could impair
management and increase healthcare cost.
1
Evidence has
shown increased mortality from these events like
myocardial infarction, hypertension, stroke and
ultimately heart failure. Changes in myocardial
malfunctioning will reflect in BP alteration, HR and ECG
changes, including ventricular dysfunctions.
2
Drugs like
doxorubicin are known to precipitate cardiac malfunction
even in therapeutic doses. Doxorubicin is an effective
chemotherapeutic agent used in the treatment of many
types of cancers. Reports from studies indicate that it
causes cardiac toxicity and this adverse effect limits the
use of the drug particularly in some patients’ categories.
3
Evidence show that the mechanism of doxorubicin
toxicity is by reducing adenosine monophosphate
activated protein kinase alpha (AMPKα) signalling in the
heart.
4
The inhibition of this signalling pathway causes
cellular energy deficits.
5
Metformin on the other hand is
ABSTRACT
Background: Cardiovascular complications during drug therapy is worrisome
and has been known to increase morbidity and mortality. The aim of this study
was to investigate the effect of metformin on BP, HR, and ECG, after subacute
administration of doxorubicin in rats.
Methods: Laboratory acclimatised animals were divided into 4 experimental
groups consisting of group I as the control, given 0.5ml normal saline. Group II,
received 3mg/kg doxorubicin on alternate days, while group III was given
300mg/kg metformin. The last group of animals were treated with 300mg/kg
metformin, 30 min later, the animals were injected doxorubicin ip. The
treatment lasted for 15 days thereafter, ECG, HR and BP were measured with
anaesthesia.
Results: Result showed that doxorubicin induced ECG changes in terms of
increased PR and QT intervals significantly. Whereas, QRS and RR intervals
were at same time significantly decreased. Metformin was observed to
significantly attenuate these changes. In addition, metformin restored decreases
in HR that was caused by doxorubicin in a significant fashion. However,
metformin alone produced a decrease in HR compared with control. The
observed reduced SBP and DBP produced by doxorubicin were also alleviated
by the administration of metformin. There were increases in BP parameters
measured in normotensive rats with metformin alone.
Conclusions: In conclusion, metformin was found to attenuate doxorubicin-
induced alteration in ECG pattern and restored the mechanical and
physiological functions of the rat heart. Our data further suggests monitoring of
CVS changes such as ECG particularly with drugs known to cause myocardial
injury.
Keywords: Blood pressure, Doxorubicin, ECG, Heart rate, Metformin, Rats
DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20171656
Department of Pharmaceutical
Sciences, College of Clinical
Pharmacy, King Faisal
University, Hofuf, Saudi Arabia
Received: 03 March 2017
Accepted: 01 April 2017
*Correspondence to:
Dr. Promise Madu Emeka,
Email: pemeka@kfu.ewdu.sa
Copyright: © the author(s),
publisher and licensee Medip
Academy. This is an open-
access article distributed under
the terms of the Creative
Commons Attribution Non-
Commercial License, which
permits unrestricted non-
commercial use, distribution,
and reproduction in any
medium, provided the original
work is properly cited.