Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents
Background: Acute exposure to high concentrations of microcystin-LR (MC-LR) can cause significant hepatocyte injury. Aim. To document the effects of long-term, low-dose MC-LR exposure on hepatic inflammation and fibrosis in mice with healthy and diseased livers. Material and methods: Male CD1 mice (...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-11-01
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| Series: | Annals of Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268119304648 |
| _version_ | 1819107352771559424 |
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| author | Meaghan Labine Yuewen Gong Gerald Y. Minuk |
| author_facet | Meaghan Labine Yuewen Gong Gerald Y. Minuk |
| author_sort | Meaghan Labine |
| collection | DOAJ |
| description | Background: Acute exposure to high concentrations of microcystin-LR (MC-LR) can cause significant hepatocyte injury. Aim. To document the effects of long-term, low-dose MC-LR exposure on hepatic inflammation and fibrosis in mice with healthy and diseased livers. Material and methods: Male CD1 mice (N = 20/group) were exposed to 1.0 μg/L of MC-LR in drinking water; 1.0 μg/L MC-LR plus 300 mg/L of the hepatotoxin thioacetamide (MC-LR/TAA); or 300 mg/L TAA alone for 28 weeks. Liver biochemistry and histology were documented at the end of the study period. In addition, hepatic stellate cells (HSCs), were exposed in vitro to MC-LR (0.1-10,000 μg/L) and monitored for changes in cell metabolism, proliferation and activation. Results: Liver biochemistry and histology were essentially normal in MC-LR alone exposed mice. MC-LR/TAA and TAA alone exposed mice had significant hepatic inflammation and fibrosis but the extent of the changes were similar in the two groups. In vitro, MC-LR had no effect on HSC metabolism, proliferation or activation. Conclusion: Long-term, low-dose exposure to MC-LR is unlikely to lead to chronic liver disease in the setting of a normal liver or exacerbate existing liver disease in the setting of ongoing hepatitis. |
| first_indexed | 2024-12-22T02:52:41Z |
| format | Article |
| id | doaj.art-f014729ee0bb41cc8cc1a4ce8815881f |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-12-22T02:52:41Z |
| publishDate | 2017-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-f014729ee0bb41cc8cc1a4ce8815881f2022-12-21T18:41:21ZengElsevierAnnals of Hepatology1665-26812017-11-01166959965Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in RodentsMeaghan Labine0Yuewen Gong1Gerald Y. Minuk2Department of Pharmacology and Therapeutics, Faculties of Medicine. University of Manitoba,Winnipeg,Manitoba,CanadaPharmacy. University of Manitoba,Winnipeg,Manitoba,CanadaDepartment of Pharmacology and Therapeutics, Faculties of Medicine. University of Manitoba,Winnipeg,Manitoba,Canada; Correspondence and reprint request: G.Y. Minuk, M.D. Morberg Family Chair in Hepatology University of Manitoba. John Buhler Research Centre 715 McDermot Ave. Winnipeg, MB R3E 3P4 Phone: (204) 789-3204. Fax: (204) 789-3987Background: Acute exposure to high concentrations of microcystin-LR (MC-LR) can cause significant hepatocyte injury. Aim. To document the effects of long-term, low-dose MC-LR exposure on hepatic inflammation and fibrosis in mice with healthy and diseased livers. Material and methods: Male CD1 mice (N = 20/group) were exposed to 1.0 μg/L of MC-LR in drinking water; 1.0 μg/L MC-LR plus 300 mg/L of the hepatotoxin thioacetamide (MC-LR/TAA); or 300 mg/L TAA alone for 28 weeks. Liver biochemistry and histology were documented at the end of the study period. In addition, hepatic stellate cells (HSCs), were exposed in vitro to MC-LR (0.1-10,000 μg/L) and monitored for changes in cell metabolism, proliferation and activation. Results: Liver biochemistry and histology were essentially normal in MC-LR alone exposed mice. MC-LR/TAA and TAA alone exposed mice had significant hepatic inflammation and fibrosis but the extent of the changes were similar in the two groups. In vitro, MC-LR had no effect on HSC metabolism, proliferation or activation. Conclusion: Long-term, low-dose exposure to MC-LR is unlikely to lead to chronic liver disease in the setting of a normal liver or exacerbate existing liver disease in the setting of ongoing hepatitis.http://www.sciencedirect.com/science/article/pii/S1665268119304648CyanobacteriaBlue-green algaeCyanotoxinsMicrocystinsHepatic fibrosisCirrhosis |
| spellingShingle | Meaghan Labine Yuewen Gong Gerald Y. Minuk Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents Annals of Hepatology Cyanobacteria Blue-green algae Cyanotoxins Microcystins Hepatic fibrosis Cirrhosis |
| title | Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents |
| title_full | Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents |
| title_fullStr | Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents |
| title_full_unstemmed | Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents |
| title_short | Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents |
| title_sort | long term low dose exposure to microcystin lr does not cause or increase the severity of liver disease in rodents |
| topic | Cyanobacteria Blue-green algae Cyanotoxins Microcystins Hepatic fibrosis Cirrhosis |
| url | http://www.sciencedirect.com/science/article/pii/S1665268119304648 |
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