Protective Effect of Beta-Caryophyllene on Doxorubicin Induced Multiple Organ Toxicity in Rats

Abstract

The major limiting factor in doxorubicin’s long-term administration is the development of cumulative dosedependent
cardiomyopathy and congestive heart failure. Also, doxorubicin causes deterioration in hepato-renal
function. It significantly increases the levels of blood urea nitrogen, creatinine, alanine transaminase, and
aspartate transaminase distortion in normal renal and hepatic histology. The present study was undertaken to
find out the protective role of beta-caryophyllene (BCP), an anti-oxidant against doxorubicin-induced multiple
organ toxicities in experimental animals. In this study, male Wistar rats were divided into four groups. The first
group, control group, was administered with vehicle (2.5% tween 20); the second group received doxorubicin
(15 mg/kg intraperitoneally at a single dose), third and fourth groups (treatment groups) received BCP plus
doxorubicin (15 mg/kg) at doses of 100 mg/kg and 200 mg/kg respectively. BCP was given orally for 15 days and
doxorubicin was given on 13th day of treatment. Cardiac function was assessed by measuring electrocardiogram
changes and cardiac biomarkers—doxorubicin-induced significant lengthening of QT-interval and ST-elevation,
which was completely prevented by BCP treatment. Doxorubicin caused oxidative stress as indicated by a significant
decrease in reduced superoxide dismutase, glutathione level, and catalase activity with an increase in
malondialdehyde compared to control. Doxorubicin and BCP significantly reversed these values compared to
doxorubicin in heart, kidney, and liver. The histopathological examination has also shown signs of toxicity in
doxorubicin treated groups, and healing effect was noticed in treatment groups.