Browsing by Subject "Thioacetamide"

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    Experimental thioacetamide-induced cirrhosis of the liver
    (Murcia : F. Hernández, 1991) Muñoz Torres, E.; Paz-Bouza, J.I.; López Bravo, A.; Abad Hernández, M.M.; Carrascal Marino, E.
    Hepatic cirrhosis is a complex disease in which several biological, biochemical and chemical alterations are combined, none of these alone being sufficient for diagnosis. The morphological characteristics of the final stages of cirrhosis are well known, but the initial lesions and intermediate stages still have not been fully clarified. An experimental model of hepatic cirrhosis by chronic administration over 30 weeks of thioacetamide (50 mglkg twice weekly) to female Wistar rats has been produced. In a macroscopic, microscopic and ultrastructural study. The different lesions that appeared were evaluated according to the dose of the toxic agent administered up, until hepatic cirrhosis was finally installed; this was after 60 doses of the toxic agent (30 weeks). Discussion is made of the different types of administration and the doses employed to obtain a suitable survival rate for these cases; in our experiments this was 95%. It has been demonstrated in both human and experimental pathology that once the disease itself has been installed, currently there is no rational or useful treatment for it. A beneficial effect has been demonstrated for certain substances, improving the initial and intermediate lesions. so we conclude by stating that it is necessary to further study the hepatic lesions preceeding cirrhosis. Knowledge of these lesions could form the basis for establishing a useful and rational therapy for such cases.
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    M1- and M2-macrophage polarization in thioacetamide (TAA)-induced rat liver lesions; a possible analysis for hepato-pathology
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Wijesundera, Kavindra Kumara; Izawa, Takeshi; Murakami, Hiroshi; Tennakoon, Anusha Hemamali; Golbar, Hossain M.; Katou-Ichikawa, Chisa; Tanaka, Miyuu; Kuwamura, Mitsuru; Yamate, Jyoji
    “Classically activated macrophages (M1)” and “alternatively activated macrophages (M2)”, which appear in injured tissues, control either inflammation or remodeling. The mechanism remains unclear. To clarify the M1-/M2-macrophage polarization in acute liver injury, M1- and M2-related factors were analysed in F344 rats by a single injection of TAA (300 mg/kg BW), and liver samples were collected on post injection (PI) hour 10 and days 1 to 10. Macrophage immunopheno-types were analyzed by single and double immuno-labeling. M1-/M2-related factors were analyzed by real-time RT-PCR. On PI hour 10 (when centrilobular lesions were not still developed), expressions of IFN-γ, TNF-α, IL-1ß, and IL-6 for M1, and IL-4 for M2 were already increased, followed by increased expressions of IL-10 and TGF-ß1 for M2 on PI days 1-3 with development of centrilobular lesions and subsequent reparative fibrosis. On PI hour 10, CD204+ and MHC class II+ macrophages already increased in the intact periportal/Glisson’s sheath regions, accompanied by an increased number of granzyme B+ NK cells. Reactive cells at PI hour 10 might produce M1-related factors. In addition to these macrophages, CD68+ and CD163+ macrophages, and CD3+ T cells appeared in the injured centrilobular region on PI days 1-3; there were macrophages reacting simultaneously to CD68/MHC class II, CD163/MHC class II, CD68/CD204, CD163/CD204, and MHC class II/CD204 in varying degrees. Although CD68+ and CD163+ macrophages are regarded as M1- and M2-types, respectively, the double labeling indicated that macrophage immunophenotypes are interchangeable in injured regions and subsequent fibrosis. An M1-/M2-macrophage paradigm would be useful to analyze hepatotoxicity and to understand the pathogenesis. Histol Histopathol 29, 497-511 (2014)
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    Protective effect of alpha-mangostin on thioacetamide-induced liver fibrosis in rats as revealed by morpho-functional analysis
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Rodniem, Siripa; Tiyao, Vilailak; Nilbu nga, Cheng; Poonkhum, Raksawan; Pongmayteegul, Sirinun; Pradidarcheep, Wisuit
    Liver fibrosis is an excessive accumulation of scar tissue resulting from inflammation and cell death. Thioacetamide (TAA) is a well-known hepatotoxin that induces liver fibrosis. A marker of injured hepatocytes is transforming growth factor-beta 1 (TGF-β1), while alpha-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinase 1 (TIMP-1) are markers of activated hepatic stellate cells. Alpha-mangostin, a major xanthone derivative from the mangosteen pericarp, has been shown to have anti-oxidant and anti-inflammatory activities. The objective of this study was to determine whether alpha-mangostin has a protective effect on TAA-induced liver fibrosis in rats. The rats were treated by intraperitoneal injection of compounds for eight weeks. For the control group a mixture of dimethyl sulfoxide and phosphate buffered saline was administered. Two hundred mg/kg BW of TAA was administered three times weekly. Alpha-mangostin was administered at 5 mg/kg BW and silymarin at 100 mg/kg BW, both twice weekly. TAA induced histologically recognizable liver damage and fibrosis, as anticipated. Furthermore, it increased immunohistochemically detectable TGF-β1, α-SMA, and TIMP-1. Coadministration of alpha-mangostin or silymarin with TAA prevented or ameliorated the effects of TAA administration alone. The anti-fibrotic effect of alphamangostin was stronger than that of silymarin.