Immunomodulatory properties of captopril, an ACE inhibitor, on LPS-induced lung inflammation and fibrosis as well as oxidative stress
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The role of angiotensin converting enzyme inhibitors on the inflammation process has been demonstrated previously. In the present study, the effects of captopril on lung injury induced by lipopolysaccharide (LPS) were investigated.
Control, LPS, 12.5, 25 and 50 mg/kg captopril-treated before LPS administration and captopril 50 mg/kg before saline administration groups of rats were studied. Total and percentage of differential WBC, the levels of MDA, total thiol groups, the activities of SOD and CAT, the levels of IFN-γ, PGE2, TGF-β1 and IL-4 in the BALF were evaluated.
MDA concentration in LPS groups treated with all captopril concentrations, total WBC in LPS + Cap50, percent of neutrophils in LPS + Cap25 and LPS + Cap50, levels of IFN-γ, PGE2, TGF-β1 in LPS + Cap50 and IFN-γ/IL-4 ratio in LPS + Cap25 and LPS + Cap50 were significantly decreased but total thiol groups and activity of SOD in LPS + Cap25 and LPS + Cap50, percent of lymphocyte, CAT activity and concentration of IL-4 only in LPS + Cap50 group were increased in comparison to the LPS group (p < 0.05 to p < 0.001).
Captopril dose dependently improved oxidant–antioxidant biomarkers, the imbalance between pro-inflammatory and anti-inflammatory cytokines and showed specific immunomodulatory effect on Th1/Th2 balance in the BALF of lung injury induced by LPS.
KeywordsCaptopril LPS Inflammation Lung Cytokines Oxidative stress
This study was financially supported by a grant from Research Council of Mashhad University of Medical Sciences. This manuscript is the results of Parma. D. Thesis of Javad Boskabadi.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
- Adage T, Del bene F, Fiorentini F, Doornbos RP, Zankl C, Bartley MR, Kungl AJ (2015) PA401, a novel CXCL8-based biologic therapeutic with increased glycosaminoglycan binding, reduces bronchoalveolar lavage neutrophils and systemic inflammatory markers in a murine model of LPS-induced lung inflammation. Cytokine 76:433–441CrossRefGoogle Scholar
- Askari VR, Fereydouni N, Baradaran rahimi V, Askari N, Sahebkar AH, Rahmanian-devin P, Samzadeh-kermani A (2018) Beta-amyrin, the cannabinoid receptors agonist, abrogates mice brain microglial cells inflammation induced by lipopolysaccharide/interferon-gamma and regulates Mphi1/Mphi2 balances. Biomed Pharmacother 101:438–446CrossRefGoogle Scholar
- Li Y, Zeng Z, Li Y, Huang W, Zhou M, Zhang X, Jiang W (2015) Angiotensin-converting enzyme inhibition attenuates lipopolysaccharide-induced lung injury by regulating the balance between angiotensin-converting enzyme and angiotensin-converting enzyme 2 and inhibiting mitogen-activated protein kinase activation. Shock 43:395–404CrossRefGoogle Scholar
- Oliveira JRMC, Greiffo FR, Rigonato-oliveira NC, Custódio RWA, Silva VR, Damaceno-rodrigues NR, Almeida FM, Albertini R, Lopes-martins RÁB, De oliveira LVF (2014) Low level laser therapy reduces acute lung inflammation in a model of pulmonary and extrapulmonary LPS-induced ARDS. J Photochem Photobiol B 134:57–63CrossRefGoogle Scholar
- Pu G, Rong J, Xin Y, Jing L, Jie D, LI Z, Bin Y (2016) The angiotensin-converting enzyme inhibitor captopril rescues mice from endotoxin-induced lethal hepatitis. Innate Immun 23:128–135Google Scholar
- Rahimi VB, Askari VR, Shirazinia R, Soheili-far S, Askari N, Rahmanian-devin P, Sanei-far Z, Mousavi SH, Ghodsi R (2018) Protective effects of hydro-ethanolic extract of Terminalia chebula on primary microglia cells and their polarization (M1/M2 balance). Mult Scler Relat Disord 25:5–13CrossRefGoogle Scholar