title: Role of oxidative stress, inflammation, nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotaline-induced pulmonary hypertension in rats.
abstract: Pulmonary hypertension is a progressive disease of various origins that is associated with right ventricular dysfunction. In the present study, the protective effect of diosgenin was investigated in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). Diosgenin (100 mg/kg) was given by oral administration once daily for 3 weeks. At the end of the experiment, mean arterial blood pressure, electrocardiography and echocardiography were recorded. Rats were then 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 contents. 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. Diosgenin treatment provided a significant improvement toward preserving hemodynamic changes and alleviating oxidative stress, inflammatory and apoptotic markers induced by monocrotaline in rats. Furthermore, diosgenin therapy prevented monocrotaline-induced changes in nitric oxide production, endothelial and inducible nitric oxide synthase protein expression as well as histological analysis. These findings support the beneficial effect of diosgenin in pulmonary hypertension induced by monocrotaline in rats.
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El Aini St., Cairo 11562, Egypt. Electronic address: lamiaahmed@Staff.cu.edu.eg.
authors: Lamiaa A
authors: LA
authors: Ahmed
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El Aini St., Cairo 11562, Egypt. Electronic address: ark_pha@hotmail.com.
authors: Al Arqam Z
authors: AA
authors: Obaid
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El Aini St., Cairo 11562, Egypt. Electronic address: halafzaki@gmail.com.
authors: Hala F
authors: HF
authors: Zaki
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El Aini St., Cairo 11562, Egypt. Electronic address: azzaagha@yahoo.com.
authors: Azza M
authors: AM
authors: Agha
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004144:Diosgenin / Q000494:pharmacology* / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / 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; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020011:Protective Agents; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D016686:Monocrotaline; 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; D005978:Glutathione; D004144:Diosgenin
keywords: Diosgenin; Monocrotaline; Nitric oxide; Oxidative stress; Pulmonary hypertension