Acute blockade of endogenous melatonin by Luzindole, with or without peripheral LPS injection, induces jejunal inflammation and morphological alterations in Swiss mice

Acute blockade of endogenous melatonin by Luzindole, with or without peripheral LPS injection, induces jejunal inflammation and morphological alterations in Swiss mice

This study investigated the acute blockade of endogenous melatonin (MLT) using Luzindole with or without systemic lipopolysaccharide (LPS) challenge and evaluated changes in inflammatory and oxidative stress markers in the mouse jejunum. Luzindole is an MT1/MT2 MLT receptor antagonist. Both receptor...

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Bibliographic Details
Published in:Brazilian journal of medical and biological research Vol. 54; no. 11; pp. 1 - e11215
Main Authors: Matos, R.S, Oria, R.B, Bruin, P.F.C, Pinto, D.V, Viana, A.F.S.C, Santos, F.A, Duarte, A.S.G, Bruin, V.M.S
Format: Journal Article
Language:English
Published: Ribeirao Preto Associacao Brasileira de Divulgacao Cientifica (ABDC) 01-01-2021
Revista Brasileira de Pesquisas Medicas
Associação Brasileira de Divulgação Científica
Subjects:
BIOLOGY
Catalase
IL-1β
Immunoblotting
Inflammation
Intestine
Jejunum
Lipopolysaccharides
LPS
Luzindole
MEDICINE, RESEARCH & EXPERIMENTAL
Melatonin
Mitogens
Morphometry
NF-κB protein
Oxidative stress
Peroxidase
Small intestine
Tumor necrosis factor
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Villus
Brazil
Oxidative stress
Melatonin
Inflammation
Intestine
Luzindole
LPS
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Summary:This study investigated the acute blockade of endogenous melatonin (MLT) using Luzindole with or without systemic lipopolysaccharide (LPS) challenge and evaluated changes in inflammatory and oxidative stress markers in the mouse jejunum. Luzindole is an MT1/MT2 MLT receptor antagonist. Both receptors occur in the small intestine. Swiss mice were treated with either saline (0.35 mg/kg, ip), Luzindole (0.35 mg/kg, ip), LPS (1.25 mg/kg, ip), or Luzindole + LPS (0.35 and 1.25 mg/kg, ip, respectively). Jejunum samples were evaluated regarding intestinal morphometry, histopathological crypt scoring, and PAS-positive villus goblet cell counting. Inflammatory Iba-1, interleukin (IL)-1 [beta], tumor necrosis factor (TNF)-[alpha], nuclear factor (NF)-kB, myeloperoxidase (MPO), and oxidative stress (NP-SHs, catalase, MDA, nitrate/nitrite) markers were assessed. Mice treated with Luzindole, LPS, and Luzindole + LPS showed villus height shortening. Crypt damage was worse in the LPS group. Luzindole, LPS, and Luzindole + LPS reduced the PAS-goblet cell labeling and increased Iba-1-immunolabelled cells compared to the saline group. Immunoblotting for IL-1 [beta], TNF-[alpha], and NF-kB was greater in the Luzindole group. The LPS-challenged group showed higher MPO activity than the saline and Luzindole groups. Catalase was reduced in the Luzindole and Luzindole + LPS groups compared to saline. The Luzindole group showed an increase in NP-SHs, an effect related to compensatory GSH activity. The acute blockade of endogenous MLT with Luzindole induced early changes in inflammatory markers with altered intestinal morphology. The other non-detectable deleterious effects of Luzindole may be balanced by the unopposed direct action of MLT in immune cells bypassing the MT1/MT2 receptors. Key words: Luzindole; Melatonin; LPS; Inflammation; Oxidative stress; Intestine
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ISSN:0100-879X
1414-431X
1414-431X
1678-4510
DOI:10.1590/1414-431X2021e11215