Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol
Studies into the mechanism of acetaminophen (APAP)-induced hepatotoxicity have focused mainly at the hepatocellular level. This study aimed to investigate the effect of acetaminophen on the hepatic microvasculature using a vascular casting technique. Acetaminophen was administered at a dose of 650 m...
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Faculty of Medicine, University of Malaya
1996
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| author | Lim, S.P. Andrews, F.J. O'Brien, P.E. |
| author_facet | Lim, S.P. Andrews, F.J. O'Brien, P.E. |
| author_sort | Lim, S.P. |
| collection | UM |
| description | Studies into the mechanism of acetaminophen (APAP)-induced hepatotoxicity have focused mainly at the hepatocellular level. This study aimed to investigate the effect of acetaminophen on the hepatic microvasculature using a vascular casting technique. Acetaminophen was administered at a dose of 650 mg/kg body weight (intraperitoneally) to fasted male Long Evans rats. Microvascular casting was performed at various points after drug administration. Liver casts from control rats showed good patency with normal hepatic microvasculature. Thirty-six hours after overdose with acetaminophen, liver casts showed rounded centrilobular cavities of various sizes, representing regions in which cast-filled sinusoids were absent with relatively normal microvasculature within periportal regions. Evidence of microvascular injury occurred as early as 5 hours after acetaminophen overdose. This injury consisted of changes to centrilobular sinusoids including areas of incomplete filling and dilated centrilobular sinusoids. Misoprostol (a prostaglandin E1 analog) treatment (6 x 25 micrograms/kg) given before and after acetaminophen administration markedly reduced the extent of microvascular injury with only small focal unfilled areas in the casts and a generally intact microvasculature. In conclusion, this study shows that overdosage with APAP resulted in an extensive, characteristic pattern of hepatic microvascular injury in the centrilobular region. The results also suggest that microvascular injury is an early event in the pathogenesis of acetaminophen hepatotoxicity. Misoprostol was found to protect against injury occurring at the microvascular level. |
| first_indexed | 2024-03-06T06:02:53Z |
| format | Article |
| id | um.eprints-24482 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T06:02:53Z |
| publishDate | 1996 |
| publisher | Faculty of Medicine, University of Malaya |
| record_format | dspace |
| spelling | um.eprints-244822021-03-24T01:50:58Z http://eprints.um.edu.my/24482/ Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol Lim, S.P. Andrews, F.J. O'Brien, P.E. R Medicine Studies into the mechanism of acetaminophen (APAP)-induced hepatotoxicity have focused mainly at the hepatocellular level. This study aimed to investigate the effect of acetaminophen on the hepatic microvasculature using a vascular casting technique. Acetaminophen was administered at a dose of 650 mg/kg body weight (intraperitoneally) to fasted male Long Evans rats. Microvascular casting was performed at various points after drug administration. Liver casts from control rats showed good patency with normal hepatic microvasculature. Thirty-six hours after overdose with acetaminophen, liver casts showed rounded centrilobular cavities of various sizes, representing regions in which cast-filled sinusoids were absent with relatively normal microvasculature within periportal regions. Evidence of microvascular injury occurred as early as 5 hours after acetaminophen overdose. This injury consisted of changes to centrilobular sinusoids including areas of incomplete filling and dilated centrilobular sinusoids. Misoprostol (a prostaglandin E1 analog) treatment (6 x 25 micrograms/kg) given before and after acetaminophen administration markedly reduced the extent of microvascular injury with only small focal unfilled areas in the casts and a generally intact microvasculature. In conclusion, this study shows that overdosage with APAP resulted in an extensive, characteristic pattern of hepatic microvascular injury in the centrilobular region. The results also suggest that microvascular injury is an early event in the pathogenesis of acetaminophen hepatotoxicity. Misoprostol was found to protect against injury occurring at the microvascular level. Faculty of Medicine, University of Malaya 1996-12 Article PeerReviewed Lim, S.P. and Andrews, F.J. and O'Brien, P.E. (1996) Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol. Journal of the University of Malaya Medical Centre (JUMMEC), 1 (2). p. 57. ISSN 1823-7339, https://jummec.um.edu.my/issue/view/661/Vol.1%2C%20No.2%2C%201996 |
| spellingShingle | R Medicine Lim, S.P. Andrews, F.J. O'Brien, P.E. Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol |
| title | Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol |
| title_full | Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol |
| title_fullStr | Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol |
| title_full_unstemmed | Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol |
| title_short | Acetaminophen-induced microvascular injury in the rat liver: protection with misoprostol |
| title_sort | acetaminophen induced microvascular injury in the rat liver protection with misoprostol |
| topic | R Medicine |
| work_keys_str_mv | AT limsp acetaminopheninducedmicrovascularinjuryintheratliverprotectionwithmisoprostol AT andrewsfj acetaminopheninducedmicrovascularinjuryintheratliverprotectionwithmisoprostol AT obrienpe acetaminopheninducedmicrovascularinjuryintheratliverprotectionwithmisoprostol |