MOLECULAR EFFECTS OF RUTIN ON DIESEL EXHAUST PARTICLEINDUCED CARDIOVASCULAR TOXICITY

Abstract

Atmospheric particulate matter (PM) is a major component of urban air pollution. Diesel Exhaust particle (DEP) is a major component of atmospheric PM in urban areas and has been extensively investigated to be associated with cardiovascular morbidity and mortality. Rutin, is a plant chemical found in buckwheat, apples etc. Research has showed it to possess antioxidant, anti-inflammatory, cardio-protective properties, but its mechanism of action is not fully elucidated. This research aims to reveal the molecular effects of rutin on DEP-induced cardiovascular toxicity in male rats. The experimental animals were divided into six groups, viz: control, rutin treated (25 mg/kg) and DEP pre-treated groups (rutin + DEP-induced groups) and DEP-induced groups (30 and 60 μg/kg). DEP was nasally instilled and rutin was administered intraperitoneally for two weeks after which the animals were sacrificed and genes of interest investigated. Genes associated with oxidative stress and proinflammatory response (IL-8, TNF-α) were upregulated significantly (p>0.05) in DEP-induced groups compared to the pretreated and treated groups. While mRNA levels of antioxidants- associated (HO-1, Nrf2) and antiinflammatory (IL-10) genes were highly expressed by rutin. DEP also altered lipid homeostasis by downregulating LDL-receptor mRNA level, and elevating PCSK9 gene expressions. Contrarily, rutin showed its ameliorative effects by upregulating LDLreceptor genes. Also, in animals exposed to DEP alone, biomarkers of cardiovascular impairments (lactate dehydrogenase, creatinine kinase enzymes and cardiac troponin (cTNI) were elevated in the tissues. The oxidative stress markers (lipid peroxidation and conjugated dienes formation) were also elevated by DEP. DEP exposure also altered the expression of vasodilatory genes (eNOs, and ACE). All of these metabolic disorders were attenuated by rutin. This research shows the molecular effects of rutin on DEPinduced cardiovascular toxicity and its oxidative potentials. It can thus be concluded that rutin has the therapeutic potential to ameliorate the cardiovascular adverse effects of diesel exhaust particulate matter in wistar rats.