Prebiotic inulin consumption reduces dioxin-like PCB 126-mediated hepatotoxicity and gut dysbiosis in hyperlipidemic Ldlr deficient mice

Abstract The aim of the research was to compare selected coagulants efficiency in indicator and chosen dioxin-like PCB removal from surface water. As coagulants, there were used aluminium sulfate and 5 hydrolyzed polyaluminium chlorides, with trade names: PAX-XL1, PAX-XL10, PAX-XL19, PAX-XL60, PAX-XL69. For the research, surface water was used, collected from dam reservoir. The water composition was modified with standard mixtures PCB MIX24 and MIX13, in order to obtain concentration of each congener equal to 300 ng/dm3. The PCB MIX24 mixture was composed of indicator congeners solution: 28, 52, 101, 118, 138, 153, and 180, whereas the MIX13 mixture - solution of three dioxin-like PCB 77, PCB 126, and PCB 169. It was demonstrated that the application of aluminium sulfate allowed for reaching better effects for purifying water of PCB, than with the usage of pre-hydrolyzed salts, polyaluminium chlorides. Out of the studied coagulants, the best effects for indicator PCB removal were obtained with the application of aluminium sulfate, total PCB concentration was decreased by 65%. The highest efficiency for indicator congeners removal (90%) was obtained for PCB 138 and 153. After the application of hydrolyzed polyaluminium chlorides PAX-XL1, PAX-XL10 decrease in higher chlorinated PCB concentration was obtained, in the range of 23 to 74%. Selectivity of chosen PCB congener removal, depending on applied coagulant, was demonstrated; with the usage of aluminium sulfate, removal of heptachlorobiphenyl PCB 180 at the level of 34% was obtained, whereas with the application of PAX-XL1 and PAX-XL10 higher reduction efficiency for this congener was obtained, i.e. 83 and 74% respectively. For dioxin-like PCB, after application of aluminium sulfate, total concentration reduction by 74% was obtained, efficiency of this congeners removal amounted to from 54 (PCB 77) up to 72% (PCB 126), similar results were obtained after the usage of PAX-XL1. The lowest PCB removal from water rate was stated for coagulants PAX-XL60 and PAX-XL69.

Download Full-text

Gut dysbiosis protects against liver injury in autophagy deficient mice by FXR-FGF15 feedback signaling

10.1101/2020.05.12.090613 ◽

2020 ◽

Author(s):

Shengmin Yan ◽

Bilon Khambu ◽

Xiaoyun Chen ◽

Zheng Dong ◽

Grace Guo ◽

...

Keyword(s):

Liver Disease ◽

Growth Factor ◽

Liver Injury ◽

Fibroblast Growth Factor ◽

Liver Diseases ◽

Farnesoid X Receptor ◽

List Type ◽

Fibroblast Growth ◽

Gut Dysbiosis ◽

Deficient Mice

ABSTRACTObjectiveThe gut microbiota (GM) can have complicated and often undetermined interactions with the function of many organs in the body. GM is altered in a variety of liver diseases, but the significance of such changes on the liver disease is still unclear. Hepatic autophagy deficiency causes liver injury accompanied with cholestasis. Here, we investigated the impact of such hepatic changes on GM and in turn the effect of gut dysbiosis on liver injury.DesignFecal microbiota from mice with liver-specific loss of autophagy-related gene 5 (Atg5), Atg5Δhep mice, were analyzed by 16S sequencing. Antibiotics (ABX) was used to modulate GM in mice. Cholestyramine was used to reduce the enterohepatic bile acid (BA) level. The functional role of fibroblast growth factor 15 (FGF15) and ileal farnesoid X receptor (FXR) was examined in mice over-expressing FGF15 gene, or given a fibroblast growth factor receptor 4 (FGFR4) inhibitor.ResultsThe composition of GM was significantly changed with a notable increase of BA-metabolizing bacteria in Atg5Δhep mice, leading to a lower proportion of tauro-conjugated BAs and a higher proportion of unconjugated BAs in the intestine, which markedly activated ileal FXR with an increased expression of FGF15. ABX or cholestyramine treatment exacerbated liver injury and ductular reaction, and decreased FGF15 expression, whereas modulating FGF15 signaling altered liver phenotypes in the autophagy-deficient mice.ConclusionGut dysbiosis can remedy liver injury in Atg5Δhep mice through the FXR-FGF15 signaling. Antibiotics use in the condition of liver injury may have unexpected adverse consequences via the gut-liver axis.SHORT SUMMARYWhat is already known about this subject?Gut microbiota (GM) can be altered during hepatic pathogenesis.GM are involved in bile acid (BA) metabolism.Autophagy deficiency in the liver disrupts BA homeostasis and causes cholestatic injury.What are the new findings?Deficiency of autophagy in the liver causes alteration of GM, which leads to a higher proportion of BA-metabolizing bacteria.GM contribute to the activation of ileal farnesoid X receptor (FXR) and a higher expression of fibroblast growth factor 15 (FGF15) in autophagy deficient condition in the liver, which is associated with decreased levels of conjugated BAs and increased levels of unconjugated BAs in the intestine.Manipulations that lead to GM alteration, intestinal BA signaling, or FGF15 signaling can all modulate the liver phenotype.BA and GM together can act as a sensor to liver injury to trigger FGF15-mediated protective mechanism.How might it impact on clinical practice in the foreseeable future?These findings indicate that gut dysbiosis in the scenario of liver disease can be beneficial, suggesting cautions should be exercised in the use of antibiotics during specific liver diseases.If antibiotics need to be used in patients with liver diseases it may be beneficial to enhance the FXR-FGF15 feedback signaling to retain the protective effect of GM.

Download Full-text

Effects of the dioxin-like PCB 126 on larval summer flounder (Paralichthys dentatus)

Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology ◽

10.1016/j.cbpc.2010.02.006 ◽

2010 ◽

Vol 152 (1) ◽

pp. 9-17 ◽

Cited By ~ 5

Author(s):

Bruno Soffientino ◽

Diane E. Nacci ◽

Jennifer L. Specker

Keyword(s):

Summer Flounder ◽

Paralichthys Dentatus ◽

Pcb 126 ◽

Dioxin Like Pcb

Download Full-text

Gut dysbiosis with decreased Akkermansia muciniphila and differential expression of tumor‐associated genes contribute to a tumor‐preventive microenvironment in intestinal epithelial Pten‐deficient mice

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.484.10 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Sang Hoon Rhee ◽

Cody Howe ◽

Su Jin Kim ◽

Jonathon Mitchell ◽

Eunok Im

Keyword(s):

Differential Expression ◽

Intestinal Epithelial ◽

Akkermansia Muciniphila ◽

Gut Dysbiosis ◽

Deficient Mice

Download Full-text

Responses of paraoxonase 1 to dioxin-like pcb 126 ( 3,3',4,4',5-pentachlorobiphenyl)

10.17077/etd.3dqb6nvc ◽

2011 ◽

Author(s):

Hua Shen

Keyword(s):

Paraoxonase 1 ◽

Pcb 126 ◽

Dioxin Like Pcb

Download Full-text

Developmental toxicity, oxidative stress, and related gene expression induced by dioxin-like PCB 126 in zebrafish (Danio rerio)

Environmental Toxicology ◽

10.1002/tox.22044 ◽

2014 ◽

Vol 31 (3) ◽

pp. 295-303 ◽

Cited By ~ 20

Author(s):

Han Liu ◽

Fang-Hong Nie ◽

Hong-Ying Lin ◽

Yi Ma ◽

Xiang-Hong Ju ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Danio Rerio ◽

Developmental Toxicity ◽

Related Gene ◽

Pcb 126 ◽

Dioxin Like Pcb

Download Full-text

Dioxin-like PCB 126 increases intestinal inflammation and disrupts gut microbiota and metabolic homeostasis

Environmental Pollution ◽

10.1016/j.envpol.2018.07.039 ◽

2018 ◽

Vol 242 ◽

pp. 1022-1032 ◽

Cited By ~ 38

Author(s):

Michael C. Petriello ◽

Jessie B. Hoffman ◽

Olga Vsevolozhskaya ◽

Andrew J. Morris ◽

Bernhard Hennig

Keyword(s):

Gut Microbiota ◽

Intestinal Inflammation ◽

Metabolic Homeostasis ◽

Pcb 126 ◽

Dioxin Like Pcb

Download Full-text

Comparison of localization of metallothionein in tissues of metallothionein-deficient mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141585 ◽

1995 ◽

Vol 53 ◽

pp. 1042-1043

Author(s):

H. Nishimura ◽

R Nishimura ◽

D.L. Adelson ◽

A.E. Michaelska ◽

K.H.A. Choo ◽

...

Keyword(s):

Metal Binding ◽

Immunohistochemical Staining ◽

Squamous Epithelium ◽

Rabbit Antiserum ◽

Slight Modification ◽

Positive Control ◽

Heavy Metal Binding ◽

Critical Organ ◽

Metal Binding Protein ◽

Deficient Mice

Metallothionein (MT), a cysteine-rich heavy metal binding protein, has several isoforms designated from I to IV. Its major isoforms, I and II, can be induced by heavy metals like cadmium (Cd) and, are present in various organs of man and animals. Rodent testes are a critical organ to Cd and it is still a controversial matter whether MT exists in the testis although it is clear that MT is not induced by Cd in this tissue. MT-IV mRNA was found to localize within tongue squamous epithelium. Whether MT-III is present mainly glial cells or neurons has become a debatable topic. In the present study, we have utilized MT-I and II gene targeted mice and compared MT localization in various tissues from both MT-deficient mice and C57Black/6J mice (C57BL) which were used as an MT-positive control. For MT immunostaining, we have used rabbit antiserum against rat MT-I known to cross-react with mammalian MT-I and II and human MT-III. Immunohistochemical staining was conducted by the method described in the previous paper with a slight modification after the tissues were fixed in HistoChoice and embedded in paraffin.

Download Full-text