Ethyl pyruvate ameliorates monocrotaline-induced pulmonary arterial hypertension in rats.
BACKGROUND
Ethyl pyruvate (EP) is an anti-inflammatory and anti-oxidant agent associated with many diseases. In this study, we evaluated whether EP could attenuate monocrotaline-induced pulmonary arterial hypertension (PAH).


METHODS
A PAH model was established by subcutaneously injecting a single dose of monocrotaline (60 mg/kg). And then a daily intraperitoneal injection of EP (50 mg/kg) was administered on day 1 to day 28 (preventive EP treatment) or day 15 to day 28 (therapeutic EP treatment). Hemodynamic changes were measured by catheterization, and the right ventricle hypertrophy index, the medial wall thickness, and the medial wall areas were also calculated. Enzyme-linked immunosorbent assay and immunohistochemical analysis were used to determine the serum levels and expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and endothelin-1 (ET-1) in the lung tissue.


RESULTS
Both preventive and therapeutic EP treatment significantly ameliorated hemodynamic changes and vascular remodeling indicators (all P < 0.05). The serum levels and expression of TNF-α, IL-6, and ET-1 in the lung tissue were also significantly decreased (all P < 0.05).


CONCLUSIONS
EP ameliorates monocrotaline-induced PAH and reverses pulmonary vascular remolding in rats by inhibiting the release of TNF-α and IL-6 and reducing the expression of ET-1.
Departments of *Cardiovascular Surgery; †Geriatric Medicine; and ‡Department of Clinical Medicine, Qilu Hospital, School of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Chuanzhen
C
Liu
Changcun
C
Fang
Guangqing
G
Cao
Kai
K
Liu
Biao
B
Wang
Zhaojie
Z
Wan
Sijie
S
Li
Shuming
S
Wu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D019332:Endothelin-1 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D011773:Pyruvates / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D019332:Endothelin-1; D015850:Interleukin-6; D011773:Pyruvates; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D016686:Monocrotaline