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Effects of partial hepatectomy on organ‐specific toxic response to 1,2‐dibromo‐3‐chloropropane (DBCP)
Author(s) -
Kluwe William M.
Publication year - 1983
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550030402
Subject(s) - epididymis , hepatectomy , medicine , endocrinology , kidney , necrosis , toxicity , chemistry , andrology , surgery , resection , sperm
The organ‐specific toxic potency of subcutaneously administered 1,2‐dibromo‐3‐chloropropane (DBCP) was compared in partially hepatectomized and sham‐operated rats over a dose range of 20–80 mg kg −1 to assess the roles of hepatic and extrahepatic metabolism in protection against acute renal and gonadal injury. Relative kidney weight and the severity of DBCP‐induced renal proximal tubular cell necrosis were increased in rats subjected to a partial (70%) surgical hepatectomy 48 h prior to treatment with DBCP at 80 mg kg −1 . Relative liver weight was reduced by DBCP in the hepatectomized, but not in the shamoperated, rats. The severity of DBCP‐induced (80 mg kg −1 ) hepatocellular centrilobular necrosis was greater in hepatectomized than in sham rats. DBCP reduced the relative weights of the testis and epididymis in a progressive manner and produced dose‐dependent seminiferous tubular atrophy within 12 days of treatment. The morphologically apparent lesions of the testis and epididymis were enhanced by hepatectomy. The concentration of non‐protein sulfhydryl groups (NPS) in rat liver was increased by partial hepatectomy. Because of the resulting decrease in liver size, however, the total amount of hepatic NPS per kg body weight 48 h post‐surgery was lower than in sham rats. The surgery had no effect on renal, testicular or epididymal NPS concentrations or organ weights. Partial hepatectomy greatly increased pentobarbital and ethanol sleeping times, while sleep induction time for pentobarbital was decreased. These results are consistent with previous studies indicating that the metabolism of DBCP and conjugation with glutathione in the liver protects extrahepatic organs from toxic insult. Moreover, since extrahepatic toxicity was still evident, and often enhanced, after partial hepatectomy, extrahepatic necrogenic or cytotoxic responses would not appear to be dependent on hepatic metabolism of DBCP to a direct toxicant.