Biochemical and molecular effects of naringenin on the cardiovascular oxidative and pro-inflammatory effects of oral exposure to diesel exhaust particles in rats

Abstract

Studies have shown that diesel exhaust particle (DEP), a typical air particulate matter (PM) component of diesel exhaust, exerts its toxic effects by inducing oxidative and pro-inflammatory effects. Naringenin is the predominant flavanone in citrus fruits and has been reported to possess antioxidant, anti-inflammatory, anti-carcinogenic, and anti-mutagenic effects. This study examined the effects of naringenin on the oxidative and inflammatory effects of DEP in aorta and heart of Wistar rats. Diesel exhaust particle collected from a vehicular source in Akure, Nigeria, was extracted in methanol, fractionated and characterized by GCMS. Forty male Wistar rats (80–90 g) were divided into 8 groups. These rats were exposed to either methanol extract of SRM 2975 (mSRM; 0.064 mg/kg) DEP or collected diesel exhaust particles (mDEP; 0.064 or 0.64 mg/kg) sample in the presence or absence of naringenin (50 mg/kg). Both the DEP extracts and naringenin (NAR) were administered by oral gavage. The molecular interactions of NAR with target proteins associated with DEP toxicity were determined using in silico approach. The results show that both mDEP and mSRM caused significant (p < 0.001) decrease in serum HDL but increase serum AST/ALT ratio, ALP, LDL, triacylglycerol (TG), total cholesterol (TC), tissue conjugated dienes (CD) and MDA levels. The extracts also significantly (p < 0.001) increased the expression of IL-1β, TNFα, NF-κB, IκB, and IκKB in the aorta and heart, but decreased Nrf2, HO1, and anti-inflammatory IL-10 mRNA levels when compared with control. Pretreatment with NAR significantly (p < 0.001) reversed all these DEP-induced effects in both tissues. In conclusion, naringenin has the potential to mitigate DEP-induced oxidative stress and inflammation and thus may serve as a therapeutic agent against air pollution-induced cardiovascular damage.