PMID- 32018220 OWN - NLM STAT- MEDLINE DCOM- 20201126 LR - 20201126 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 125 DP - 2020 May TI - Investigation of protective effects of apilarnil against lipopolysaccharide induced liver injury in rats via TLR 4/ HMGB-1/ NF-kappaB pathway. PG - 109967 LID - S0753-3322(20)30157-8 [pii] LID - 10.1016/j.biopha.2020.109967 [doi] AB - Sepsis caused by infection is one of the most important problems of clinical medicine. This study aimed to determine the effect of Apilarnil (API), a bee product, on lipopolysaccharide (LPS) induced liver injury. In the study, 64 adult Sprague-Dawley rats were divided into eight groups; control, 0.2, 0.4 and 0.8 g / kg apilarnil (API) treated groups, LPS (30 mg / kg) group, LPS + 0.2, LPS + 0.4 and LPS + 0.8 g / kg API. At tissues obtained from rats, histopathological evaluation, biochemical analysis by ELISA (Catalase-CAT, malondialdehyde-MDA, superoxide dismutase-SOD, xanthine oxidase-XOD, and testican 1-TCN-1), immunohistochemical evaluation (Toll-like receptor 4 (TLR4), High Mobility Group Box Protein 1 (HMGB-1), nuclear factor kappa B (NF-kappaB), Tumor necrosis factor-alpha (TNF-alpha), Interleukin 1 beta (IL-1beta), Interleukin 6 (IL-6) and Inducible nitric oxide (iNOS)), TUNEL analysis to determine the number of apoptotic cells and Comet test as an indicator of DNA damage were performed. Histopathological examination revealed dilated blood vessels, inflammatory cell infiltration, and pyknotic nuclei damaged hepatocytes in the liver tissues of the LPS group. It was found that tissue damage was decreased significantly in LPS + API treatment groups compared to the LPS group. The number of TUNEL positive cells observed in the LPS group in liver samples increased compared to control and API-treated groups only (p < 0.05). The number of TUNEL positive cells showed a statistically significant decrease compared to the LPS group in the groups treated with LPS + API. LPS treatment increased MDA, XOD, and TCN 1 levels and decreased SOD and CAT levels; this effect was reversed in the groups treated with LPS + API. In the LPS group, DNA damage was significantly increased when compared with the LPS + API. LPS treatment increased expression of TLR4, HMGB-1, NF-kappaB, iNOS, TNF-alpha, IL-1beta, IL-6; in the groups treated with LPS + API reduced this increase. In conclusion, apilarnil administered in rats may be thought to prevent LPS-induced liver damage by inhibiting the TLR4 / HMGB-1 / NF-kappaB signaling pathway. CI - Copyright (c) 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Doganyigit, Zuleyha AU - Doganyigit Z AD - Yozgat Bozok University, Faculty of Medicine, Department of Histology and Embryology, Erdogan Akdag Campus, Yozgat, Turkey. Electronic address: zuleyha.doganyigit@yobu.edu.tr. FAU - Okan, Asli AU - Okan A AD - Yozgat Bozok University, Faculty of Medicine, Department of Histology and Embryology, Erdogan Akdag Campus, Yozgat, Turkey. Electronic address: oflamaz.asly@gmail.com. FAU - Kaymak, Emin AU - Kaymak E AD - Yozgat Bozok University, Faculty of Medicine, Department of Histology and Embryology, Erdogan Akdag Campus, Yozgat, Turkey. Electronic address: e_kaymak@hotmail.com. FAU - Pandir, Dilek AU - Pandir D AD - Yozgat Bozok University, Faculty of Arts and Science, Department of Biology, Erdogan Akdag Campus, Yozgat, Turkey. Electronic address: dilek.pandir@yobu.edu.tr. FAU - Silici, Sibel AU - Silici S AD - Erciyes University, Seyrani Faculty of Agriculture, Department of Agricultural Biotechnology, Kayseri, Turkey. Electronic address: silicis@erciyes.edu.tr. LA - eng PT - Journal Article DEP - 20200202 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Biological Products) RN - 0 (HMGB1 Protein) RN - 0 (Hbp1 protein, rat) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Tlr4 protein, rat) RN - 0 (Toll-Like Receptor 4) RN - 0 (apilarnil) SB - IM MH - Animals MH - Biological Products/*therapeutic use MH - Chemical and Drug Induced Liver Injury/*prevention & control MH - Gene Expression Regulation/drug effects MH - HMGB1 Protein/genetics/*metabolism MH - Lipopolysaccharides/*toxicity MH - NF-kappa B/genetics/*metabolism MH - Rats MH - Toll-Like Receptor 4/genetics/*metabolism OTO - NOTNLM OT - Apilarnil OT - Apoptosis OT - Inflammation OT - LPS OT - Liver OT - Oxidative stress COIS- Declaration of Competing Interest There is no conflict of interest among the authors. EDAT- 2020/02/06 06:00 MHDA- 2020/11/27 06:00 CRDT- 2020/02/05 06:00 PHST- 2019/12/20 00:00 [received] PHST- 2020/01/20 00:00 [revised] PHST- 2020/01/26 00:00 [accepted] PHST- 2020/02/06 06:00 [pubmed] PHST- 2020/11/27 06:00 [medline] PHST- 2020/02/05 06:00 [entrez] AID - S0753-3322(20)30157-8 [pii] AID - 10.1016/j.biopha.2020.109967 [doi] PST - ppublish SO - Biomed Pharmacother. 2020 May;125:109967. doi: 10.1016/j.biopha.2020.109967. Epub 2020 Feb 2.