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

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2020-03, Vol.127, p.154957, Article 154957
• Main Authors: Savran, M., Aslankoc, R., Ozmen, O., Erzurumlu, Y., Savas, H.B., Temel, E.N., Kosar, P.A., Boztepe, S.
• Format: Article
• Language: English
• 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
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2019.154957

•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.