Agomelatine could prevent brain and cerebellum injury against LPS-induced neuroinflammation in rats

•Neuroinflammation, oxidative stress, and apoptosis act in LPS-induced brain damage.•Agomelatine has antioxidant, antiinflammatory and antiapoptotic features.•Agomelatine effects on platelet count should be invesitigated in further studies. Sepsis, systemic hyper-inflammatory immune response, causes...

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Published in:	Cytokine (Philadelphia, Pa.) Vol. 127; p. 154957
Main Authors:	Savran, M., Aslankoc, R., Ozmen, O., Erzurumlu, Y., Savas, H.B., Temel, E.N., Kosar, P.A., Boztepe, S.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-03-2020
Subjects:	Acetamides - pharmacology Agomelatine Animals Antioxidants - metabolism Apoptosis Apoptosis - drug effects Brain Injuries - chemically induced Brain Injuries - drug therapy Brain Injuries - metabolism Cerebellum - drug effects Cerebellum - metabolism Hippocampus - drug effects Hippocampus - metabolism Inflammation Inflammation - chemically induced Inflammation - drug therapy Inflammation - metabolism Lipopolysaccharides - pharmacology Male NF-kappa B - metabolism Oxidative stress Oxidative Stress - drug effects Rats Rats, Wistar Sepsis - chemically induced Sepsis - drug therapy Sepsis - metabolism Signal Transduction - drug effects SIRT-1 SIRT-1 Oxidative stress Agomelatine Inflammation Apoptosis
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Summary:	•Neuroinflammation, oxidative stress, and apoptosis act in LPS-induced brain damage.•Agomelatine has antioxidant, antiinflammatory and antiapoptotic features.•Agomelatine effects on platelet count should be invesitigated in further studies. Sepsis, systemic hyper-inflammatory immune response, causes the increase of morbidity and mortality rates due to multi-organ diseases such as neurotoxicity. Lipopolysaccharide (LPS) induces inflammation, oxidative stress and apoptosis to cause brain damage. We aimed to evaluate the antioxidant, anti-inflammatory and antiapoptotic effects of Agomelatine (AGM) on LPS induced brain damage via NF-kB signaling. Twenty-four animals were divided into three groups as control, LPS (5 mg/kg) and LPS + AGM (20 mg/kg). Six hours after the all administrations, rats were sacrificed, brain tissues were collected for biochemical, histopathological and immunohistochemical analysis. In LPS group; total oxidant status (TOS), OSI index, Caspase-8 (Cas-8), NF-kß levels increased and Total antioxidant status (TAS) levels decreased biochemically and Cas-8, haptoglobin and IL-10 expressions increased and sirtuin-1 (SIRT-1) levels decreased immunohistochemically. AGM treatment reversed these parameters except haptoglobin levels in hippocampus and SIRT-1 levels in cerebellum. Besides, AGM treatment blocked the phosphorylation of NF-kB biochemically and ameliorated increased the levels of hyperemia, edema and degenerative changes histopathologically. In conclusion, AGM enhanced SIRT-1 levels to negatively regulate the transcription and activation of p-NF-kB/p65 which caused to ameliorate inflammation, oxidative stress and apoptosis.
ISSN:	1043-4666 1096-0023
DOI:	10.1016/j.cyto.2019.154957