Effect of Angiotensin‑converting Enzyme Inhibitor on Cardiac Fibrosis and Oxidative Stress Status in Lipopolysaccharide‑induced Inflammation Model in Rats

Azam Abareshi, Fatemeh Norouzi, Fereshteh Asgharzadeh, Farimah Beheshti, Mahmoud Hosseini, Mehdi Farzadnia, Majid Khazaei

Abstract


Background: Renin‑angiotensin (Ang)‑aldosterone system not only plays a key role in the regulation of circulatory homeostasis, but also it acts as a powerful pro‑inflammatory mediator. The aim of this study was to evaluate the effect of captopril (Cap), a known Ang‑converting enzyme inhibitor, on inflammation‑induced cardiac fbrosis, and heart oxidative stress status in
lipopolysaccharide (LPS)‑induced inflammation in male rats.

Methods: Fifty male rats were randomly divided into fve groups control, LPS (1 mg/kg/day), LPS + Cap 10 mg/kg, LPS + Cap 50 mg/kg and LPS + Cap 100 mg/kg. After 2 weeks, blood samples were taken, and hearts were harvested for evaluation of tumor necrosis factor alpha (TNF‑α), interleukin‑6 (IL‑6) and nitric oxide metabolite in serum and tissue hemogenate, histopathology (hematoxylin and eosin and Masson’s
trichrome) and oxidative stress status.

Results: Serum IL‑6 and TNF‑α concentration were higher in LPS group compared to control and Cap reduced them, signifcantly. Heart TNF‑α and IL‑6 contents in LPS group were signifcantly higher than control (P < 0.05). The administration of Cap signifcantly decreased inflammatory markers level to control (P < 0.05). The higher levels of malondialdehyde and lower antioxidative markers (total thiol, superoxide dismutase, and catalase)
in the heart were observed in LPS group and treatment by Cap improved them, dose‑dependently. Histopathological study revealed cardiac fbrosis and more collagen content in LPS group which signifcantly improved by Cap treatment.

Conclusions: Treatment by Cap reduced cardiac fbrosis possibly through improving oxidative stress status, and it can be considered to increase cardiac compliance in this condition.

Keywords: Angiotensin, cardiac, fbrosis, inflammation


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