RESUMO
Acetaminophen (APAP) overdose is one of the major causes of acute liver failure. Severe liver inflammation and the production of oxidative stress occur due to toxic APAP metabolites and glutathione depletion. Growing evidence has proved that vitamin D (VD) exerts anti-inflammatory and antioxidative functions. Our objective was to explore the protective role of calcitriol (VD3) in acute APAP-induced liver injury. Methods: Adult male mice were randomized into three groups; control (n = 8), APAP (n = 8), and VD3 group (n = 8). All mice, except controls, received oral administration of APAP (400 mg/kg) and were sacrificed 24 h later. In the VD3 group, calcitriol (10 µg/kg) was injected intraperitoneally 24 h before and after exposure to APAP. Blood samples were collected to assess serum aminotransferase and inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)]. Liver tissues were analyzed for hepatic glutathione (GSH), malondialdehyde (MDA), and histopathology. Results: APAP administration significantly increased serum aminotransferase, inflammatory cytokines, and induced cellular inflammation and necrosis. APAP also depleted hepatic GSH and elevated oxidative stress, as indicated by high MDA levels. In the APAP group, 25% of the mice (two out of eight) died, while no deaths occurred in the VD3 group. Treatment with calcitriol significantly reduced serum aminotransferase, TNF-α, and IL-6 levels in the VD3 group compared to the APAP group. Additionally, VD3 effectively restored GSH reserves, reduced lipid peroxidation, and attenuated hepatotoxicity. Conclusions: These findings demonstrate that VD3 prevents APAP-induced acute liver injury and reduces mortality in mice through its anti-inflammatory and antioxidative activity. Thus, VD3 might be a novel treatment strategy for APAP-induced hepatotoxicity.
RESUMO
BACKGROUND: Endoscopists' experience influences narrow-band imaging (NBI)-guided gastric intestinal metaplasia (GIM) diagnostic performance. We aimed to evaluate the general gastroenterologists (GE) performance in NBI-guided GIM diagnosis compared to NBI experts (XP) and assess GEs' learning curve. METHODS: A cross-sectional study was conducted between 10/2019 and 2/2022. Histology-proven GIM who underwent esophagogastroduodenoscopy (EGD) were randomly assessed by 2XPs or 3GEs. Endoscopists' performance on NBI-guided diagnoses were compared to the pathological diagnosis (gold standard) in five areas of the stomach according to the Sydney protocol. The primary outcome were GIM diagnosis validity scores of GEs compared to XPs. The secondary outcome was the minimum number of lesions required for GEs to achieve an accuracy of GIM diagnosis ≥ 80%. RESULTS: One thousand one hundred and fifty-five lesions from 189 patients (51.3% male, mean age 66 ± 10 years) were examined. GEs performed EGD in 128 patients with 690 lesions. the GIM diagnosis sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of GEs compared to the XPs, were 91% vs.93%, 73% vs.83%, 79% vs.83%, 89% vs.93%, and 83% vs.88%, respectively. GEs demonstrated lower specificity (mean difference - 9.4%; 95%CI - 16.3, 1.4; p = 0.008) and accuracy (mean difference - 5.1%; 95%CI - 3.3, 6.3; p = 0.006) compared to XPs. After 100 lesions (50% GIM), GEs achieved an accuracy of ≥ 80% and all diagnostic validity scores were comparable to the XPs (p < 0.05 all). CONCLUSIONS: Compared to XPs, GEs had lower specificity and accuracy for GIM diagnosis. The learning curve for a GE to achieve comparable performance to XPs would necessitate at least 50 GIM lesions. Created with BioRender.com.