Potentiation of carbon tetrachloride hepatotoxicity by pentosan polysulfate in rats
Braz. j. med. biol. res
; 35(11): 1339-1346, Nov. 2002. ilus, tab, graf
Article
in English
| LILACS
| ID: lil-326247
Responsible library:
BR1.1
RESUMO
Few data are available in the literature regarding the effect of pentosan polysulfate (PPS) on normal and fibrotic rat livers. In addition, the combination of PPS and carbon tetrachloride (CCl4) has not been studied so far. The objective of this study was to assess the effect of PPS on rat livers treated or not with CCl4 for the induction of liver fibrosis. The study consisted of four stages 1) hepatic fibrosis induction with CCl4 (N = 36 rats); 2) evaluation of the effect of PPS on CCl4-induced hepatic fibrosis (N = 36 rats); 3) evaluation of the effect of higher doses of PPS in combination with CCl4 (N = 50 rats); 4) evaluation of the presence of an enzymatic inductor effect by PPS (N = 18 rats) using the sodium pentobarbital test which indirectly evaluates hepatic microsomal enzyme activity in vivo. Adult (60 to 70 days) male Wistar rats weighing 180 to 220 g were used. All animals receiving 0.5 ml 8 percent CCl4 (N = 36) developed hepatic fibrosis, and after 8 weeks they also developed cirrhosis. No delay or prevention of hepatic fibrosis was observed with the administration of 5 mg/kg PPS (N = 8) and 1 mg/kg PPS (N = 8) 1 h after the administration of CCl4, but the increased hepatotoxicity resulting from the combination of the two substances caused massive hepatic necrosis in most rats (N = 45). PPS (40 mg/kg) alone caused hepatic congestion only after 8 weeks, but massive hepatic necrosis was again observed in association with 0.5 ml CCl4 after 1 to 4 weeks of treatment. Unexpectedly, sleeping time increased with time of PPS administration (1, 2, or 3 weeks). This suggests that PPS does not function as an activator of the hepatic microsomal enzymatic system. Further studies are necessary in order to clarify the unexpected increase in hepatotoxicity caused by the combination of CCl4 and high doses of PPS, which results in massive hepatic necrosis
Full text:
Available
Collection:
International databases
Database:
LILACS
Main subject:
Pentosan Sulfuric Polyester
/
Carbon Tetrachloride
/
Enzyme Inhibitors
/
Liver
Limits:
Animals
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
2002
Document type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
Universidade Federal do Rio Grande do Sul/BR