thioacetamide and Thrombocytopenia

Thrombocytopenia is usually associated with liver injury, elevated plasma aspartate aminotransferase and alanine aminotransferase levels, and high antiplatelet immunoglobulin (Ig) titers, although the mechanism behind these effects remains elusive. Deciphering the mechanism behind acute liver disease-associated thrombocytopenia may help solve difficulties in routine patient care, such as liver biopsy, antiviral therapy, and surgery. To determine whether liver damage is sufficient per se to elicit thrombocytopenia, thioacetamide (TAA)-induced hepatitis rodent models were employed. The analysis results indicated that TAA treatment transiently induced an elevation of antiplatelet antibody titer in both rats and mice. B-cell-deficient (BCD) mice, which have loss of antibody expression, exhibited markedly less thrombocytopenia and liver damage than wild-type controls. Because TAA still induces liver damage in BCD mice, this suggests that antiplatelet Ig is one of the pathogenic factors, which play exacerbating role in the acute phase of TAA-induced hepatitis. TNF-α was differentially regulated in wild-type versus BCD mice during TAA treatment, and anti-TNF treatment drastically ameliorated antiplatelet Ig induction, thrombocytopenia, and liver injury, suggesting that the TNF pathway plays a critical role in the disease progression.

Topics: Animals; Antigens, Human Platelet; Autoantibodies; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Disease Progression; Humans; Male; Mice; Rats; Thioacetamide; Thrombocytopenia; Tumor Necrosis Factor-alpha

This study was designed to evaluate hematological disorders and the orchestrating roles of hepcidin and IL-6 in rat models of thioacetamide (TAA) and carbon tetrachloride (CCl4) hepatotoxicity.. Rats were intraperitoneally injected with TAA (10 mg/100 g rat weight dissolved in isosaline) or CCl4 (100 μL/100 g rat weight diluted as 1:4 in corn oil) twice weekly for eight consecutive weeks to induce subchronic liver fibrosis. Blood and tissue samples were collected and analyzed.. CCl4 but not TAA significantly decreased the RBCs, Hb, PCV, and MCV values with minimal alterations in other erythrocytic indices. Both hepatotoxins showed leukocytosis, granulocytosis, and thrombocytopenia. By the end of the experiment, the erythropoietin level increased in the CCl4 model. The serum iron, UIBC, TIBC, transferrin saturation%, and serum transferrin concentration values significantly decreased, whereas that of ferritin increased in the CCl4 model. TAA increased the iron parameters toward iron overload. RT-PCR analysis revealed increased expression of hepatic hepcidin and IL-6 mRNAs in the CCl4 model and suppressed hepcidin expression without significant effect on IL-6 in the TAA model.. These data suggest differences driven by hepcidin and IL-6 expression between CCl4 and TAA liver fibrosis models and are of clinical importance for diagnosis and therapeutics of liver diseases.

Topics: Animals; Blood Chemical Analysis; Carbon Tetrachloride; Hepcidins; Injections, Intraperitoneal; Interleukin-6; Iron; Leukocytosis; Liver Cirrhosis; Male; Rats; Thioacetamide; Thrombocytopenia; Transferrin

Topics: Animals; Catheter Ablation; Electromagnetic Phenomena; Hypersplenism; Liver Cirrhosis, Experimental; Methylcellulose; Rats; Splenectomy; Thioacetamide; Thrombocytopenia; Time Factors

Thrombocytopenia due to hypersplenism is usually a serious condition in cirrhotic patients who have undergone invasive procedures. We designed a new treatment method using a high-frequency alternating electromagnetic force to treat the disease condition in a rat model.. Sprague-Dawley rats were given thioacetamide in drinking water and injected with methylcellulose intraperitoneally to create a cirrhotic hypersplenism model. Spleen volume was determined using the Carlson method. The Control Group consisted of 14 rats, 15 weeks old, that were used to determine the normal platelet count and normal spleen size. Experimental Group I, consisting of 15 rats, received electromagnetic thermoablation of their spleens, after which the spleen was returned to the abdomen. Group II consisted of 13 rats, receiving the same electromagnetic thermoablation as Group I, but the ablated portion was removed. Group III consisted of 14 rats receiving total splenectomies.. Cirrhotic hypersplenism was confirmed during laparotomy and pathological examination. Spleen volume enlarged from 1513 +/- 375 mm(3) (Control Group) to 7943 +/- 2822 mm(3) (experimental groups). Platelet counts increased from 0.35 +/- 0.21 x 10(6)/mm(3) to 0.87 +/- 0.24 x 10(6)/mm(3) for Group I, from 0.52 +/- 0.23 x 10(6)/mm(3) to 1.10 +/- 0.20 x 10(6)/mm(3) for Group II, and from 0.47 +/- 0.23 x 10(6)/mm(3) to 1.18 +/- 0.26 x 10(6)/mm(3) for Group III. No rats died due to the treatment in any of the experimental groups.. Our animal model performed successfully and our proposed electromagnetic thermotherapy effectively treated thrombocytopenia due to cirrhotic hypersplenism.

Topics: Animals; Catheter Ablation; Electromagnetic Phenomena; Hypersplenism; Liver Cirrhosis, Experimental; Male; Methylcellulose; Platelet Count; Rats; Rats, Sprague-Dawley; Splenectomy; Thioacetamide; Thrombocytopenia; Time Factors