Thioacetamide-induced liver damage and thrombocytopenia is associated with induction of antiplatelet autoantibody in mice

Abstract

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.

Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling

“…Furthermore, proteins by pending of NF-κB signaling pathway were normalized by GF ( Figure 3 E,F). Our findings are well comprised of the representative pathophysiological status of hepatic inflammation by TAA-induced hepatic liver injury [ 22 , 23 ] and sufficient to support anti-hepatic inflammation effects on liver fibrosis by attenuations of pro-inflammatory cytokines as well as Kupffer cells activation related molecules ( Figure 3 A–F).…”

Silver Nanoparticles Protect Skin from Ultraviolet B-Induced Damage in Mice

“…Wild-type male C57BL/6J mice (6–8 weeks old) were purchased from the National Laboratory Animal Center and housed in the Laboratory Animal Center, Tzu-Chi University, until they were 8–9 weeks old [ 31 , 42 ]. The hair on the backs of the mice was removed using a commercial hair removal cream containing thioglycolate trihydrate (approximately 250 µL/mouse) 2–3 days prior to the UVB-irradiation experiments.…”

“…The samples were placed on ice during processing. TNF–α, IL–1β, IL–6, and IL–10 levels in the skin, which represents the degree of inflammation, were measured using ELISA kits (BioLegend, San Diego, CA, USA), following previously described methods [ 31 , 42 ]. For histological examination, the skin tissues were cut into three strips, preserved in 4% formaldehyde solution, dehydrated, and embedded in paraffin wax.…”

“…For histological examination, the skin tissues were cut into three strips, preserved in 4% formaldehyde solution, dehydrated, and embedded in paraffin wax. The tissue sectioning and hematoxylin–eosin (H&E) staining were conducted following previously described methods [ 31 , 42 ]. Thickness from the stratum granulosum to the stratum basale of the skin samples were measured at three random sites on each tissue strip [ 31 ].…”

Suppressed humoral immunity is associated with dengue nonstructural protein NS1-elicited anti-death receptor antibody fractions in mice

“…Using SDS-PAGE and NIH-Image J software (version 1.6.2), the purified Igs were estimated approximately 87%-91% pure. Experimental mice and rabbits were maintained at a specific pathogen free condition with consistent temperature and humidity controls, and 12 h light/dark cycles [75][76][77] . All protocols used in rabbit and mouse experiments were carried out in accordance with the guidelines of and approved by the Institutional Animal Care and Use Committee of Tzu-Chi University (approval ID: 101019).…”