The effects of naringenin on oxidative stress parameters in cardiac muscles of diabetic rats.

Abstract

Introduction: Diabetic cardiomyopathy (DCM) is defined by hypertrophy, oxidative stress, fibrosis and inflammation of the cardiac muscle. Hyperglycemia-associated oxidative stress plays an important role in the development of cardiac hypertrophy. Naringenin a citrus fruitderived flavonoid has previously been demonstrated to have antioxidant, anti-diabetic, antiinflammatory and cardioprotective properties by as yet unknown mechanisms. Aim: To investigate the effects of naringenin on oxidative stress parameters in cardiac muscles of diabetic rats. Methods: Wister rats (250-300g) were randomly divided into six groups (n=7). Groups I and IV were orally treated daily for 56 days with 3.0 ml/ kg Body Weight (BW) of distilled water and 60 mg/kg BW of naringenin in distilled water, respectively. Groups II, III, V and VI were made diabetic by a single intraperitoneal injection of 60 mg/kg BW of streptozotocin (STZ) and similarly treated with naringenin, except group VI which was treated with insulin 2.0 U/BW bid. Group V was pre-treated with naringenin for a period of one week before STZ administration. On day 57 the animals were euthanized, blood samples collected, and the hearts were excised, weighed and stored at -80ᴼC. Antioxidant activity (catalase, glutathione peroxidase and superoxide dismutase) was measured using colorimetric commercial kits. Malondialdehyde (MDA) levels were measured using the Thiobarbituric acid reactive substances assay (TBARS) while fasting plasma insulin was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit and insulin resistance was calculated using Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and pro-inflammatory cytokine levels were measured by commercial ELISA kits.

Results: Diabetic animals presented with significant (p< 0.05) weight loss, polydipsia, increased fasting blood glucose (FBG) levels and glucose intolerance (GI) compared to control. Naringenin treatment significantly increased antioxidant enzyme levels (cardiac tissue) in diabetic animals compared to the untreated diabetic groups. MDA and TNF-α levels (in cardiac tissue) were significantly increased in the untreated diabetic groups compared to the control. Cardiac mass to body weight ratio was increased in the untreated diabetic rats compared to the naringenin treated diabetic rats. Conclusion: Naringenin pre-treatment and naringenin post STZ treatment improved diabetic symptoms, antioxidant levels, heart weights and reduced inflammation suggesting its cardioprotective effects in diabetic cardiomyopathy are due to its antioxidant properties.