Methylene dianiline

Acute toxicity and effects on biliary function

Mary F. Kanz, Lata Kaphalia, Bhupendra Kaphalia, Eleonora Romagnoli, Ghulam Ansari

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

4,4′-Methylene dianiline (4,4′-diaminodiphenylmethane, DAPM), which is used in the polymer industry, causes hepatobiliary damage in exposed humans. Our objectives were to characterize the acute toxicity of DAPM in liver, particularly on secretion of biliary constituents and on biliary epithelial cell γ-glutamyl transpeptidase (GGT) activity. Biliary cannulas were positioned in Sprague-Dawley male rats under pentobarbital anesthesia. After 1 hr of control bile collection, each rat was given 250 mg DAPM/kg (50 mg/ml) po in 35% ethanol or 35% ethanol only; bile was collected for a further 4 hr. Groups of rats were also examined for liver injury and biliary function at 8 and 24 hr after DAPM. Four hours after DAPM administration, main bile duct cells were severely damaged with minimal damage to peripheral bile ductule cells. Focal periportal hepatocellular necrosis and extensive cytolysis of cortical thymocytes occurred by 24 hr. Serum indicators of liver injury were elevated by 4 hr and continued to rise through 24 hr. By 4 hr, biliary protein concentration was increased 4-fold while concentrations of biliary bile salt, bilirubin, and glutathione were decreased by ∼80, 50, and 200%, respectively. DAPM also induced a striking effect on biliary glucose with an ∼ 20-fold increase. Histochemical staining of main bile duct GGT was absent by 8 hr after DAPM. Bile flow was diminished by 40% at 4 hr; three of five rats had no bile flow by 8 hr and none had any bile flow by 24 hr. These results indicate that DAPM rapidly diminishes bile flow and alters the secretion of biliary constituents and is highly injurious to biliary epithelial cells.

Original languageEnglish (US)
Pages (from-to)88-97
Number of pages10
JournalToxicology and Applied Pharmacology
Volume117
Issue number1
DOIs
StatePublished - 1992

Fingerprint

Bile
Toxicity
Rats
Liver
Ducts
Ethanol
gamma-Glutamyltransferase
Bile Ducts
Pentobarbital
Bile Acids and Salts
Bilirubin
Glutathione
Epithelial Cells
Polymers
Glucose
Wounds and Injuries
Thymocytes
Sprague Dawley Rats
Industry
Necrosis

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Methylene dianiline : Acute toxicity and effects on biliary function. / Kanz, Mary F.; Kaphalia, Lata; Kaphalia, Bhupendra; Romagnoli, Eleonora; Ansari, Ghulam.

In: Toxicology and Applied Pharmacology, Vol. 117, No. 1, 1992, p. 88-97.

Research output: Contribution to journalArticle

Kanz, Mary F. ; Kaphalia, Lata ; Kaphalia, Bhupendra ; Romagnoli, Eleonora ; Ansari, Ghulam. / Methylene dianiline : Acute toxicity and effects on biliary function. In: Toxicology and Applied Pharmacology. 1992 ; Vol. 117, No. 1. pp. 88-97.
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