Co-administration of lipopolysaccharide and d-galactosamine induces genotoxicity in mouse liver

Abstract The acute liver injury (ALI) and hepatic fibrosis caused by the co-treatment of lipopolysaccharide (LPS)/d-galactosamine (D-GalN) have been extensively studied. However, whether LPS/D-GalN are genotoxic has been left unknown. In this study, male mice were divided into eight groups with eigh...

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Autores principales:	Wenjing Dong, Erqun Song, Yang Song
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c9a5744ca4794edb9ad95e26955b2b1e
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spelling	oai:doaj.org-article:c9a5744ca4794edb9ad95e26955b2b1e2021-12-02T11:50:40ZCo-administration of lipopolysaccharide and d-galactosamine induces genotoxicity in mouse liver10.1038/s41598-021-81383-52045-2322https://doaj.org/article/c9a5744ca4794edb9ad95e26955b2b1e2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81383-5https://doaj.org/toc/2045-2322Abstract The acute liver injury (ALI) and hepatic fibrosis caused by the co-treatment of lipopolysaccharide (LPS)/d-galactosamine (D-GalN) have been extensively studied. However, whether LPS/D-GalN are genotoxic has been left unknown. In this study, male mice were divided into eight groups with eight animals in each group. For acute challenge of LPS/D-GalN, the mice in each group received a combination of LPS/D-GalN via intraperitoneal injection at the dose of 25 μg/kg/250 mg/kg, 25 μg/kg/500 mg/kg, or 50 μg/kg/500 mg/kg body weight. An additional group for chronic administration of test compounds was conducted by i.p. injection of LPS/D-GalN (10 μg/kg/100 mg/kg) every other day for 8 weeks. Saline solution (0.9%) and cyclophosphamide (CTX) (50 mg/kg body weight) given by i.p. injection was used as the negative and positive control, respectively. The results of single cell gel electrophoresis (SCGE) assay indicated that acute exposure of the mice to LPS/D-GalN caused severe DNA damage in hepatic cells, but not in the brain, sperm or bone marrow cells, which evidenced the genotoxicity of LPS/D-GalN administrated in combination. Interestingly, the chronic administration of LPS/D-GalN triggered significant genotoxic effects not only in hepatic but also in brain cells, with negative results in sperm and bone marrow cells. Histopathological examination in the liver and brain tissues revealed changes consistent with the SCGE results. The present study indicates genotoxic potential of LPS/D-GalN co-administered in mice, which may serve as an in vivo experimental model for relevant genotoxic study.Wenjing DongErqun SongYang SongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wenjing Dong Erqun Song Yang Song Co-administration of lipopolysaccharide and d-galactosamine induces genotoxicity in mouse liver
description	Abstract The acute liver injury (ALI) and hepatic fibrosis caused by the co-treatment of lipopolysaccharide (LPS)/d-galactosamine (D-GalN) have been extensively studied. However, whether LPS/D-GalN are genotoxic has been left unknown. In this study, male mice were divided into eight groups with eight animals in each group. For acute challenge of LPS/D-GalN, the mice in each group received a combination of LPS/D-GalN via intraperitoneal injection at the dose of 25 μg/kg/250 mg/kg, 25 μg/kg/500 mg/kg, or 50 μg/kg/500 mg/kg body weight. An additional group for chronic administration of test compounds was conducted by i.p. injection of LPS/D-GalN (10 μg/kg/100 mg/kg) every other day for 8 weeks. Saline solution (0.9%) and cyclophosphamide (CTX) (50 mg/kg body weight) given by i.p. injection was used as the negative and positive control, respectively. The results of single cell gel electrophoresis (SCGE) assay indicated that acute exposure of the mice to LPS/D-GalN caused severe DNA damage in hepatic cells, but not in the brain, sperm or bone marrow cells, which evidenced the genotoxicity of LPS/D-GalN administrated in combination. Interestingly, the chronic administration of LPS/D-GalN triggered significant genotoxic effects not only in hepatic but also in brain cells, with negative results in sperm and bone marrow cells. Histopathological examination in the liver and brain tissues revealed changes consistent with the SCGE results. The present study indicates genotoxic potential of LPS/D-GalN co-administered in mice, which may serve as an in vivo experimental model for relevant genotoxic study.
format	article
author	Wenjing Dong Erqun Song Yang Song
author_facet	Wenjing Dong Erqun Song Yang Song
author_sort	Wenjing Dong
title	Co-administration of lipopolysaccharide and d-galactosamine induces genotoxicity in mouse liver
title_short	Co-administration of lipopolysaccharide and d-galactosamine induces genotoxicity in mouse liver
title_full	Co-administration of lipopolysaccharide and d-galactosamine induces genotoxicity in mouse liver
title_fullStr	Co-administration of lipopolysaccharide and d-galactosamine induces genotoxicity in mouse liver
title_full_unstemmed	Co-administration of lipopolysaccharide and d-galactosamine induces genotoxicity in mouse liver
title_sort	co-administration of lipopolysaccharide and d-galactosamine induces genotoxicity in mouse liver
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c9a5744ca4794edb9ad95e26955b2b1e
work_keys_str_mv	AT wenjingdong coadministrationoflipopolysaccharideanddgalactosamineinducesgenotoxicityinmouseliver AT erqunsong coadministrationoflipopolysaccharideanddgalactosamineinducesgenotoxicityinmouseliver AT yangsong coadministrationoflipopolysaccharideanddgalactosamineinducesgenotoxicityinmouseliver
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Co-administration of lipopolysaccharide and d-galactosamine induces genotoxicity in mouse liver

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