Partial contribution of biliary metabolites to nephrotoxicity, renal content and excretion of [14C]hexachloro-1,3-butadiene in rats

✍ Scribed by J. P. Payan; D. Beydon; J. P. Fabry; G. Morei; M. T. Brondeau; M. Ban; J. de Ceaurriz

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 528 KB
• Volume: 13
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.2550130106

✦ Synopsis

Male Sprague Dawley rats with cannulated bile duct (BDC rats) received 100 or 200 mg kg-I labelled hexachloro-l,3-butadiene ([I4C]HCBD) by gavage 1 h (BDCI rats) or 24 h (BDCM rats) after surgical cannula implantation. Twenty-four hours after treatment with HCBD, rats were examined histochemically and biochemically for kidney damage. Urine, faeces, liver and kidney radioactivities were also measured in 24-h samples. Results were compared with those obtained from non-cannulated (NC) rats. Bile-duct cannulation did not completely protect against HCBD-induced kidney damage. The 24-h [I4C] urinary excretion and tissue content was 3&50% lower in BDC rats compared to NC rats and correlated well with the toxicity findings.

BDC, rats appeared to be much more resistant to HCBD treatment than BDCw rats. Since faecal [I4C] radioactivity extractible by diethyl ether at neutral pH in BDCl rats was twice that measured in BDC= rats, the greater resistance was attributed to a higher deficiency in the gastrointestinal absorption of unchanged HCBD.

The present results reveal that the biliary metabolites of HCBD are not solely responsible for kidney toxicity as previously assumed. They suggest a sinusoidal efflux of the HCBD conjugates from the liver. 45 2 5% and the temperature at ca. 21 * 1°C.