Biochemical and Molecular Effects of Rutin on Oxidative and Inflammatory Pathways in the Heart and Aorta of Diesel Exhaust Particles-Induced Toxicity in Male Rats
摘要
Diesel exhaust particles (DEPs) are components of atmospheric particulate matter in urban areas and have been linked to cardiovascular dysfunction. Rutin, a phytochemical, has been shown to possess many biological activities. This research aims to reveal the biochemical and molecular effects of rutin on the methanol extract of diesel exhaust particle (mDEP)-induced cardiovascular toxicity in male rats. Thirty rats were divided into six groups (n = 5); some were exposed to 30 and 60 µg/kg mDEP, while other groups were prophylactically treated with rutin (25 mg/kg). Antioxidant markers (GR, SOD, GPx, and CAT) were assessed using standard procedures. Molecular docking of rutin with selected proteins was done using AutoDock Vina. The physicochemical and pharmacokinetics of rutin were also evaluated using SwissADME. Oxidative stress (Nrf2, HO-1, NF-ĸb) and inflammatory biomarkers (IL-8, TNF-α, IL-10) were investigated using RT-PCR in the heart and aorta of mDEP-exposed rats. Exposure to mDEP significantly (p < 0.001) downregulated Nrf2, HO-1, and IL-10, but upregulated the expressions of NF-κB, IL-8, and TNF-α in the hearts and aortas of experimental rats in comparison to the control. All these effects were reversed by rutin in pre-treated rats. Rutin increased the activities of GR, GPx, and CAT compared to the mDEP-induced untreated groups. Rutin exhibits strong binding affinities with Nrf2, HO-1, and IL-10. The study suggests that rutin may protect against DEP-induced cardiovascular toxicity through a mechanism involving modulation of the antioxidant and inflammatory pathways.