title: Naringenin adds to the protective effect of L-arginine in monocrotaline-induced pulmonary hypertension in rats: favorable modulation of oxidative stress, inflammation and nitric oxide.
abstract: The present study was directed to investigate the possible modulatory effect of naringenin when co-administered with L-arginine in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). L-arginine (500 mg/kg) and naringenin (50 mg/kg) were orally administered daily, alone and in combination, for 3 weeks. Mean arterial blood pressure, electrocardiography and echocardiography were then recorded and rats were sacrificed and serum was separated for determination of total nitrate/nitrite level. Right ventricles and lungs were isolated for estimation of oxidative stress markers, tumor necrosis factor-alpha, total nitrate/nitrite and transforming growth factor-beta. Myeloperoxidase and caspase-3 activities in addition to endothelial and inducible nitric oxide synthase protein expression were also determined. Moreover, histological analysis of pulmonary arteries and cardiomyocyte cross-sectional area was performed. Combined therapy provided a significant improvement in L-arginine protective effect toward preserving hemodynamic changes and alleviating oxidative stress, inflammatory and apoptotic markers induced by monocrotaline treatment. Furthermore, combined therapy prevented monocrotaline-induced changes in endothelial and inducible nitric oxide synthase protein expression as well as histological analysis compared with either treatment alone. In conclusion, naringenin significantly adds to the protective effect of L-arginine in pulmonary hypertension induced by monocrotaline in rats.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt. Electronic address: lamiaahmed@Staff.cu.edu.eg.
authors.forename: Lamiaa A
authors.initials: LA
authors.lastname: Ahmed
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt.
authors.forename: Al Arqam Z
authors.initials: AA
authors.lastname: Obaid
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt.
authors.forename: Hala F
authors.initials: HF
authors.lastname: Zaki
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt.
authors.forename: Azza M
authors.initials: AM
authors.lastname: Agha
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D044950:Flavanones; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D016686:Monocrotaline; D001120:Arginine; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D053148:Caspase 3; C005273:naringenin
keywords: Monocrotaline; Naringenin; Pulmonary hypertension; l-arginine