Monocrotaline Toxicity Alters the Function of Hepatocyte Membrane Transporters in Rats
Pyrrolizidine alkaloid monocrotaline (MCT) induces sinusoidal obstruction syndrome (SOS) in rats characterised by a sinusoidal congestive obstruction. Additionally, MCT administration decreases the biliary excretion of gadobenate dimeglumine (BOPTA), a hepatobiliary substrate used in clinical imagin...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/14/7928 |
| _version_ | 1797446452893450240 |
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| author | Catherine M. Pastor Valérie Vilgrain |
| author_facet | Catherine M. Pastor Valérie Vilgrain |
| author_sort | Catherine M. Pastor |
| collection | DOAJ |
| description | Pyrrolizidine alkaloid monocrotaline (MCT) induces sinusoidal obstruction syndrome (SOS) in rats characterised by a sinusoidal congestive obstruction. Additionally, MCT administration decreases the biliary excretion of gadobenate dimeglumine (BOPTA), a hepatobiliary substrate used in clinical imaging. BOPTA crosses hepatocyte membranes through organic anion transporting polypeptides, multidrug-resistance-associated protein 2, and Mrp3/4 transporters, and a modified function of these transporters is likely to explain the decreased biliary excretion. This study compared BOPTA transport across hepatocytes in livers isolated from normal (Nl) rats and rats with intragastric administration of MCT. BOPTA hepatocyte influx clearance was similar in both groups, while biliary clearance and bile concentrations were much lower in MCT than in Nl livers. BOPTA efflux clearance back to the sinusoids compensated for the low biliary excretion, and hepatocyte concentrations remained similar in both groups. This SOS-associated changes of transporter functions might impact the pharmacokinetics of numerous drugs that use similar transporters to cross hepatocytes. |
| first_indexed | 2024-03-09T13:41:43Z |
| format | Article |
| id | doaj.art-c972b351be7e488fb0bd7b79141f277d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:41:43Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c972b351be7e488fb0bd7b79141f277d2023-11-30T21:06:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314792810.3390/ijms23147928Monocrotaline Toxicity Alters the Function of Hepatocyte Membrane Transporters in RatsCatherine M. Pastor0Valérie Vilgrain1Department of Radiology, University Hospital of Geneva, 1205 Geneva, SwitzerlandCentre de Recherche sur L’inflammation, Inserm, U1149, CNRS, ERL8252, 75006 Paris, FrancePyrrolizidine alkaloid monocrotaline (MCT) induces sinusoidal obstruction syndrome (SOS) in rats characterised by a sinusoidal congestive obstruction. Additionally, MCT administration decreases the biliary excretion of gadobenate dimeglumine (BOPTA), a hepatobiliary substrate used in clinical imaging. BOPTA crosses hepatocyte membranes through organic anion transporting polypeptides, multidrug-resistance-associated protein 2, and Mrp3/4 transporters, and a modified function of these transporters is likely to explain the decreased biliary excretion. This study compared BOPTA transport across hepatocytes in livers isolated from normal (Nl) rats and rats with intragastric administration of MCT. BOPTA hepatocyte influx clearance was similar in both groups, while biliary clearance and bile concentrations were much lower in MCT than in Nl livers. BOPTA efflux clearance back to the sinusoids compensated for the low biliary excretion, and hepatocyte concentrations remained similar in both groups. This SOS-associated changes of transporter functions might impact the pharmacokinetics of numerous drugs that use similar transporters to cross hepatocytes.https://www.mdpi.com/1422-0067/23/14/7928sinusoidal obstruction syndromehepatocyte transportersperfused rat livershepatocyte concentrationsclearances |
| spellingShingle | Catherine M. Pastor Valérie Vilgrain Monocrotaline Toxicity Alters the Function of Hepatocyte Membrane Transporters in Rats International Journal of Molecular Sciences sinusoidal obstruction syndrome hepatocyte transporters perfused rat livers hepatocyte concentrations clearances |
| title | Monocrotaline Toxicity Alters the Function of Hepatocyte Membrane Transporters in Rats |
| title_full | Monocrotaline Toxicity Alters the Function of Hepatocyte Membrane Transporters in Rats |
| title_fullStr | Monocrotaline Toxicity Alters the Function of Hepatocyte Membrane Transporters in Rats |
| title_full_unstemmed | Monocrotaline Toxicity Alters the Function of Hepatocyte Membrane Transporters in Rats |
| title_short | Monocrotaline Toxicity Alters the Function of Hepatocyte Membrane Transporters in Rats |
| title_sort | monocrotaline toxicity alters the function of hepatocyte membrane transporters in rats |
| topic | sinusoidal obstruction syndrome hepatocyte transporters perfused rat livers hepatocyte concentrations clearances |
| url | https://www.mdpi.com/1422-0067/23/14/7928 |
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