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Ethylene glycol poisoning induces nephrolithiasis including complement-fibrinogen-related renal tubular injury in rats.

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Τίτλος: Ethylene glycol poisoning induces nephrolithiasis including complement-fibrinogen-related renal tubular injury in rats.
Συγγραφείς: Unuma K; Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (ST), Tokyo, Japan., Isa S; Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (ST), Tokyo, Japan., Noritake K; Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (ST), Tokyo, Japan., Yamada A; Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (ST), Tokyo, Japan., Aki T; Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (ST), Tokyo, Japan. Electronic address: aki.t.9be2@m.isct.ac.jp., Tojo A; Department of Nephrology & Hypertension, Dokkyo Medical University, Tochigi, Japan.
Πηγή: Toxicology [Toxicology] 2026 Aug; Vol. 524, pp. 154470. Date of Electronic Publication: 2026 Apr 15.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: Ireland NLM ID: 0361055 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3185 (Electronic) Linking ISSN: 0300483X NLM ISO Abbreviation: Toxicology Subsets: MEDLINE
Imprint Name(s): Publication: Limerick : Elsevier
Original Publication: Amsterdam. Elsevier/North-Holland.
Ιατρικοί όροι (MeSH): Ethylene Glycol*/poisoning , Ethylene Glycol*/toxicity , Fibrinogen*/metabolism , Fibrinogen*/genetics , Nephrolithiasis*/chemically induced , Nephrolithiasis*/pathology , Nephrolithiasis*/metabolism , Kidney Tubules*/drug effects , Kidney Tubules*/metabolism , Kidney Tubules, Proximal*/drug effects , Kidney Tubules, Proximal*/ultrastructure , Kidney Tubules, Proximal*/metabolism, Animals ; Male ; Rats ; Microscopy, Electron, Transmission ; Rats, Sprague-Dawley
Περίληψη: Renal tubular damage is one of the hallmarks of ethylene glycol (EG) poisoning and is associated with calcium oxalate crystals in the kidney. We firstly conducted transcriptome analysis to search novel mechanisms of renal toxicity during EG intoxication (8 g/kg body weight, orally, 2 and 5 days) in rat kidney. Biochemical parameters in urine as well as blood plasma showed transient kidney injury that peaked at 2 days and recovered by 5 days after the administration of EG. Transcriptome analysis indicated the inductions of all fibrinogen genes (Fga, Fgb, and Fgg) and several complement components on day 2 and 5, respectively, suggesting the possible involvement of complement-fibrinogen in renal tubular injury. Immunostaining showed C3c and fibrinogen to be increased in renal tubules on day 2 of EG intoxication, confirming that the complement-fibrinogen axis may play a role in EG-related nephrolithiasis. Transmission electron microscopy (TEM) of proximal tubules showed fluid accumulations that may include EG metabolite oxalate, as well as autophagosomes containing ribosomes on days 2-5 of EG administration. TEM also indicated brush border injury in the proximal tubules, confirming renal injury after EG administration. These results revealed that the increase of complement components and fibrinogen results in aberrant deposition of these products. These findings should be beneficial for understanding the pathogenesis of EG-induced nephrolithiasis.
(Copyright © 2026 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Toshihiko Aki reports financial support was provided by The Ministry of Education, Culture, Sports, Science, and Technology. Kana Unuma reports financial support was provided by The Ministry of Education, Culture, Sports, Science, and Technology. Toshihiko Aki reports a relationship with The Ministry of Education, Culture, Sports, Science, and Technology that includes: funding grants. Kana Unuma reports a relationship with The Ministry of Education, Culture, Sports, Science, and Technology that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: C3; Ethylene glycol; Fibrinogen; Kidney; Rat
Substance Nomenclature: FC72KVT52F (Ethylene Glycol)
9001-32-5 (Fibrinogen)
Entry Date(s): Date Created: 20260416 Date Completed: 20260715 Latest Revision: 20260715
Update Code: 20260715
DOI: 10.1016/j.tox.2026.154470
PMID: 41991143
Βάση Δεδομένων: MEDLINE
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  Data: Ethylene glycol poisoning induces nephrolithiasis including complement-fibrinogen-related renal tubular injury in rats.
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  Data: <searchLink fieldCode="AU" term="%22Unuma+K%22">Unuma K</searchLink>; Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (ST), Tokyo, Japan.<br /><searchLink fieldCode="AU" term="%22Isa+S%22">Isa S</searchLink>; Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (ST), Tokyo, Japan.<br /><searchLink fieldCode="AU" term="%22Noritake+K%22">Noritake K</searchLink>; Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (ST), Tokyo, Japan.<br /><searchLink fieldCode="AU" term="%22Yamada+A%22">Yamada A</searchLink>; Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (ST), Tokyo, Japan.<br /><searchLink fieldCode="AU" term="%22Aki+T%22">Aki T</searchLink>; Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (ST), Tokyo, Japan. Electronic address: aki.t.9be2@m.isct.ac.jp.<br /><searchLink fieldCode="AU" term="%22Tojo+A%22">Tojo A</searchLink>; Department of Nephrology & Hypertension, Dokkyo Medical University, Tochigi, Japan.
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  Data: <searchLink fieldCode="MM" term="%22Ethylene+Glycol%22">Ethylene Glycol*</searchLink>/<searchLink fieldCode="MM" term="%22Ethylene+Glycol+poisoning%22">poisoning</searchLink> <br /><searchLink fieldCode="MM" term="%22Ethylene+Glycol%22">Ethylene Glycol*</searchLink>/<searchLink fieldCode="MM" term="%22Ethylene+Glycol+toxicity%22">toxicity</searchLink> <br /><searchLink fieldCode="MM" term="%22Fibrinogen%22">Fibrinogen*</searchLink>/<searchLink fieldCode="MM" term="%22Fibrinogen+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Fibrinogen%22">Fibrinogen*</searchLink>/<searchLink fieldCode="MM" term="%22Fibrinogen+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Nephrolithiasis%22">Nephrolithiasis*</searchLink>/<searchLink fieldCode="MM" term="%22Nephrolithiasis+chemically+induced%22">chemically induced</searchLink> <br /><searchLink fieldCode="MM" term="%22Nephrolithiasis%22">Nephrolithiasis*</searchLink>/<searchLink fieldCode="MM" term="%22Nephrolithiasis+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Nephrolithiasis%22">Nephrolithiasis*</searchLink>/<searchLink fieldCode="MM" term="%22Nephrolithiasis+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Kidney+Tubules%22">Kidney Tubules*</searchLink>/<searchLink fieldCode="MM" term="%22Kidney+Tubules+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Kidney+Tubules%22">Kidney Tubules*</searchLink>/<searchLink fieldCode="MM" term="%22Kidney+Tubules+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Kidney+Tubules%2C+Proximal%22">Kidney Tubules, Proximal*</searchLink>/<searchLink fieldCode="MM" term="%22Kidney+Tubules%2C+Proximal+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Kidney+Tubules%2C+Proximal%22">Kidney Tubules, Proximal*</searchLink>/<searchLink fieldCode="MM" term="%22Kidney+Tubules%2C+Proximal+ultrastructure%22">ultrastructure</searchLink> <br /><searchLink fieldCode="MM" term="%22Kidney+Tubules%2C+Proximal%22">Kidney Tubules, Proximal*</searchLink>/<searchLink fieldCode="MM" term="%22Kidney+Tubules%2C+Proximal+metabolism%22">metabolism</searchLink><br /><searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%22">Rats</searchLink> ; <searchLink fieldCode="MH" term="%22Microscopy%2C+Electron%2C+Transmission%22">Microscopy, Electron, Transmission</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%2C+Sprague-Dawley%22">Rats, Sprague-Dawley</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Renal tubular damage is one of the hallmarks of ethylene glycol (EG) poisoning and is associated with calcium oxalate crystals in the kidney. We firstly conducted transcriptome analysis to search novel mechanisms of renal toxicity during EG intoxication (8 g/kg body weight, orally, 2 and 5 days) in rat kidney. Biochemical parameters in urine as well as blood plasma showed transient kidney injury that peaked at 2 days and recovered by 5 days after the administration of EG. Transcriptome analysis indicated the inductions of all fibrinogen genes (Fga, Fgb, and Fgg) and several complement components on day 2 and 5, respectively, suggesting the possible involvement of complement-fibrinogen in renal tubular injury. Immunostaining showed C3c and fibrinogen to be increased in renal tubules on day 2 of EG intoxication, confirming that the complement-fibrinogen axis may play a role in EG-related nephrolithiasis. Transmission electron microscopy (TEM) of proximal tubules showed fluid accumulations that may include EG metabolite oxalate, as well as autophagosomes containing ribosomes on days 2-5 of EG administration. TEM also indicated brush border injury in the proximal tubules, confirming renal injury after EG administration. These results revealed that the increase of complement components and fibrinogen results in aberrant deposition of these products. These findings should be beneficial for understanding the pathogenesis of EG-induced nephrolithiasis.<br /> (Copyright © 2026 Elsevier B.V. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Toshihiko Aki reports financial support was provided by The Ministry of Education, Culture, Sports, Science, and Technology. Kana Unuma reports financial support was provided by The Ministry of Education, Culture, Sports, Science, and Technology. Toshihiko Aki reports a relationship with The Ministry of Education, Culture, Sports, Science, and Technology that includes: funding grants. Kana Unuma reports a relationship with The Ministry of Education, Culture, Sports, Science, and Technology that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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  Data: <i>Keywords: </i>C3; Ethylene glycol; Fibrinogen; Kidney; Rat
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        Value: 10.1016/j.tox.2026.154470
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      – Code: eng
        Text: English
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        StartPage: 154470
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      – SubjectFull: Animals
        Type: general
      – SubjectFull: Male
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      – SubjectFull: Rats
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      – SubjectFull: Ethylene Glycol toxicity
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      – SubjectFull: Fibrinogen genetics
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      – SubjectFull: Nephrolithiasis chemically induced
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      – TitleFull: Ethylene glycol poisoning induces nephrolithiasis including complement-fibrinogen-related renal tubular injury in rats.
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