title: Pyrrolidine dithiocarbamate attenuates the development of monocrotaline-induced pulmonary arterial hypertension.
abstract: We aimed to demonstrate the potential protective effects of pyrrolidine dithiocarbamate (PDTC) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Adult male rats were randomly assigned to 4 groups: control group, MCT-treated rats only, MCT-injected rats treated with PDTC, and PDTC-treated rats only. Blood and tissue samples were collected after the sacrifice. Levels of malondialdehyde (MDA) were measured by using the thiobarbituric acid method. Total antioxidant status (TAS) was determined using a commercially available ImAnOx kit. A histopathological evaluation was accomplished by scoring the degree of severity. Endothelial damage of the main pulmonary artery was evaluated by immunohistochemical labeling of endothelial cells using anti-rat endothelial cell antigen 1 (RECA-1) antibody. MCT-induced right ventricular hypertrophy (RVH) was reduced significantly in the MCT+PDTC-treated group. MDA levels were significantly lowered in the MCT+PDTC-treated group. TAS was significantly higher in the MCT+PDTC-treated group when compared with the rats with PAH. Histopathological examination demonstrated that PDTC treatment reduced the development of inflammation, hemorrhage and congestion, and collagen deposition. In conclusion, PDTC attenuated PAH and protected pulmonary endothelium in rats administered MCT. These findings suggest that PDTC treatment may provide a new effective therapeutic approach in the treatment of PAH.
authors.affiliation: Zeynep Kamil Gynaecologic and Pediatric Training and Research Hospital, Department of Paediatric Cardiology, Istanbul, Turkey. taneryavuz@yahoo.com
authors.forename: Taner
authors.initials: T
authors.lastname: Yavuz
authors.forename: Ozge
authors.initials: O
authors.lastname: Uzun
authors.forename: Asli
authors.initials: A
authors.lastname: Macit
authors.forename: Cem
authors.initials: C
authors.lastname: Comunoglu
authors.forename: Ozlem
authors.initials: O
authors.lastname: Yavuz
authors.forename: Coskun
authors.initials: C
authors.lastname: Silan
authors.forename: Hatice
authors.initials: H
authors.lastname: Yuksel
authors.forename: Hayriye Ak
authors.initials: HA
authors.lastname: Yildirim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004912:Erythrocytes / Q000187:drug effects; D065627:Familial Primary Pulmonary Hypertension; D006400:Hematocrit; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016686:Monocrotaline / Q000633:toxicity; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D008315:Malondialdehyde; D016686:Monocrotaline