Evidence map›Paper›PMID 41774399›Full record

ArticleForensic toxicology2026

Acute high-dose diazepam reduces total bilirubin in bile: an experimental mouse study.

Hiroshi Tsutsumi, Ako Sasao, Ryota Hiraiwa, Kyoko Hirata, Rie Sano

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Article in Forensic toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Hiroshi TsutsumiDepartment of Forensic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. hiroshi.dike@gmail.com.ORCID 0000-0002-8597-4079
Ako SasaoDepartment of Forensic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Ryota HiraiwaDepartment of Forensic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Kyoko HirataDepartment of Forensic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Rie SanoDepartment of Forensic Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeAcute drug intoxication may impair hepatic conjugation before overt liver failure. This study examined potential conjugation disturbances by assessing changes in serum and biliary bilirubin together with vital signs after an acute high dose of diazepam in mice.

methodsMale ICR mice (n = 9 per group) received an oral dose of diazepam (720 mg/kg) or vehicle (0.5% carboxymethylcellulose sodium) and were monitored for 120 min. Pulse rate, peripheral capillary oxygen saturation (SpO₂), and respiratory rate were recorded every 5 min using a pulse oximeter. At 120 min, the mice were euthanized by cervical dislocation, and blood and bile were collected. Total bilirubin concentrations in serum and bile were measured using a colorimetric assay with a lower limit of quantification of 0.16 mg/dL.

resultsDiazepam-treated mice showed a greater decline in pulse rate than vehicle-treated mice, whereas SpO₂ and respiratory rate showed no significant between-group differences. Serum total bilirubin remained below the lower limit of quantification in all animals. By contrast, biliary total bilirubin concentrations were significantly lower in diazepam-treated mice than in vehicle controls (9.16 ± 0.76 vs. 5.31 ± 0.80 mg/dL, p = 0.01), despite comparable bile weight between groups.

conclusionsAcute high-dose diazepam selectively reduced biliary total bilirubin without marked hypoxemia or respiratory depression. These findings suggest that biliary bilirubin content may serve as a candidate marker of altered hepatic conjugation during acute diazepam intoxication and warrant further evaluation in analyses of human autopsy bile in forensic toxicology.

Indexed as

BileBilirubinDiazepamAnimalsHeart RateMaleMiceMice, Inbred ICRModels, AnimalOximetryOxygenRespiratory RateBilirubinDiazepamOxygenBileBilirubinDiazepamGlucuronidationMouse

Identifiers

PMID41774399
PMCPMC13303655

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