Effects of naringenin on cardiovascular changes in prolonged hyperglycaemia in fructose-streptozotocin induced diabetic rat model / Nurul Hannim Zaidun

Diabetes mellitus (DM) is a metabolic disease that has become a global burden. Its
complications secondary to uncontrolled hyperglycaemia cause significant increase in
the morbidity and mortality rate. Numerous natural products have been studied to
combat the disease. Naringenin, obtained from citrus-based fruits has shown potential
effects as an anti-diabetic, anti-oxidant, anti-atherosclerotic and anti-fibrotic properties
when introduced at the beginning of the diabetic disease. However, the effects of
naringenin as cardiovasculoprotective agent in tissue exposed to prolonged
hyperglycaemia has not been documented extensively. Thus, this study was aimed to
determine the effect of naringenin on cardiovascular changes after prolonged exposure
of the cardiac and aortic tissue to hyperglycaemia in a diabetic rat model. Thirty (30)
adult male Sprague-Dawley rats were used in this study. Diabetic groups were induced
with fructose and streptozotocin. After 4 weeks of induction, the rats were randomly
divided into 5 groups each consisting of 6 animals: control, control treated with
naringenin, non-treated DM, DM treated with naringenin and metformin-treated DM.
Treatment with naringenin (50 mg/kg) and metformin were continued for 5 weeks. At
the end of the experiment, the data on the weight, RBG, blood pressure and fasting
serum lipid profile were analysed. The biochemical analysis on malondialdehyde and
nitric oxide levels in the aortic tissue as well as total antioxidant and hydroxyproline
levels in the cardiac tissue were evaluated. The morphological changes in the cardiac
and aortic tissue present in the experimental rats were examined under light microscopy
using H&E, Alcian blue and Sirius red staining besides TEM. Results showed that
consumption of naringenin after prolonged hyperglycaemia (4 weeks) did not
significantly improved the blood sugar, fasting serum lipid and blood pressure.
However, naringenin had shown to improve malondialdehyde and total antioxidant
level in the aortic and cardiac tissue respectively. No significant changes were observed
on the nitric oxide level of the aorta and hydroxyproline level in the heart. Histological
analysis using light and transmission electron microscopy (TEM) showed that
naringenin ameliorated the changes in diabetic heart and aorta by reducing the cardiac
atrophy and thickness of tunica intima and media in the diabetic aorta in the
experimental animals. TEM findings showed less injury on the endothelial lining of the
diabetic aorta and reduced morphological deterioration in the mitochondria of the
diabetic cardiomyocytes. These findings suggest that introduction of naringenin after
prolonged exposure to hyperglycaemia improved the cardiovascular changes caused by
diabetes partly by reducing the oxidative stress in the diabetic aorta and heart.