Effect of gadolinium chloride on liver regeneration following thioacetamide-induced necrosis in rats
Gadolinium chloride (GD) attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. The effect of GD was studied in reference to postnecrotic liver regeneration induced in rats by thioacetamide (TA). Rats, intravenously pretreated with a single dose of GD (0.1 mmol/Kg), were i...
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Published in | International journal of molecular sciences Vol. 11; no. 11; pp. 4426 - 4440 |
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Main Authors | , , , , |
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Language | English |
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04.11.2010
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Abstract | Gadolinium chloride (GD) attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. The effect of GD was studied in reference to postnecrotic liver regeneration induced in rats by thioacetamide (TA). Rats, intravenously pretreated with a single dose of GD (0.1 mmol/Kg), were intraperitoneally injected with TA (6.6 mmol/Kg). Hepatocytes were isolated from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication, and samples of blood and liver were obtained. Parameters related to liver damage were determined in blood. In order to evaluate the mechanisms involved in the post-necrotic regenerative state, the time course of DNA distribution and ploidy were assayed in isolated hepatocytes. The levels of circulating cytokine TNFα was assayed in serum samples. TNFα was also determined by RT-PCR in liver extracts. The results showed that GD significantly reduced the extent of necrosis. The effect of GD induced noticeable changes in the post-necrotic regeneration, causing an increased percentage of hepatocytes in S phase of the cell cycle. Hepatocytes increased their proliferation as a result of these changes. TNFα expression and serum level were diminished in rats pretreated with GD. Thus, GD pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. No evidence of TNFα implication in this enhancement of hepatocyte proliferation and liver regeneration was found. These results demonstrate that Kupffer cells are involved in TA-induced liver damage, as well as and also in the postnecrotic proliferative liver states. |
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AbstractList | Gadolinium chloride (GD) attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. The effect of GD was studied in reference to postnecrotic liver regeneration induced in rats by thioacetamide (TA). Rats, intravenously pretreated with a single dose of GD (0.1 mmol/Kg), were intraperitoneally injected with TA (6.6 mmol/Kg). Hepatocytes were isolated from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication, and samples of blood and liver were obtained. Parameters related to liver damage were determined in blood. In order to evaluate the mechanisms involved in the post-necrotic regenerative state, the time course of DNA distribution and ploidy were assayed in isolated hepatocytes. The levels of circulating cytokine TNFα was assayed in serum samples. TNFα was also determined by RT-PCR in liver extracts. The results showed that GD significantly reduced the extent of necrosis. The effect of GD induced noticeable changes in the post-necrotic regeneration, causing an increased percentage of hepatocytes in S phase of the cell cycle. Hepatocytes increased their proliferation as a result of these changes. TNFα expression and serum level were diminished in rats pretreated with GD. Thus, GD pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. No evidence of TNFα implication in this enhancement of hepatocyte proliferation and liver regeneration was found. These results demonstrate that Kupffer cells are involved in TA-induced liver damage, as well as and also in the postnecrotic proliferative liver states. |
Author | Cascales, María Andres, David Bautista, Mirandeli Morales-González, José A Sánchez-Reus, María Isabel |
AuthorAffiliation | 2 Instituto de Bioquímica (CSIC–UCM), Facultad de Farmacia, Ciudad Universitaria, Plaza de Ramón y Cajal S/N, 28040 Madrid, Spain; E-Mail: mireus@farm.ucm.es (M.I.S.-R.) 1 Área Académica de Farmacia, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla, 42080 Pachuca de Soto, Hgo, Mexico; E-Mail: jmorales101@yahoo.com.mx (J.A.M.-G.) |
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Author_xml | – sequence: 1 givenname: Mirandeli surname: Bautista fullname: Bautista, Mirandeli email: jmorales101@yahoo.com.mx organization: Área Académica de Farmacia, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla, 42080 Pachuca de Soto, Hgo, Mexico; E-Mail: jmorales101@yahoo.com.mx (J.A.M.-G.) – sequence: 2 givenname: David surname: Andres fullname: Andres, David – sequence: 3 givenname: María surname: Cascales fullname: Cascales, María – sequence: 4 givenname: José A surname: Morales-González fullname: Morales-González, José A – sequence: 5 givenname: María Isabel surname: Sánchez-Reus fullname: Sánchez-Reus, María Isabel |
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Keywords | kupffer cells gadolinium chloride cell cycle thioacetamide hepatotoxicity |
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SubjectTerms | Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Cell cycle Cell Proliferation Chloride Cytokines DNA - metabolism Drug dosages Gadolinium - pharmacology Gadolinium - therapeutic use gadolinium chloride Hepatectomy Hepatocytes - drug effects Hepatocytes - metabolism kupffer cells Kupffer Cells - drug effects Kupffer Cells - metabolism Liver Liver - pathology Liver Regeneration - drug effects Male Necrosis - chemically induced Necrosis - drug therapy Ploidies Rats Rats, Wistar Thioacetamide - toxicity thioacetamide hepatotoxicity Tumor Necrosis Factor-alpha - blood Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-TNF |
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Title | Effect of gadolinium chloride on liver regeneration following thioacetamide-induced necrosis in rats |
URI | https://www.ncbi.nlm.nih.gov/pubmed/21151447 https://www.proquest.com/docview/1525999963 https://pubmed.ncbi.nlm.nih.gov/PMC3000091 https://doaj.org/article/25a6a1ec286e4d0fb6656fb5dddd4b85 |
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