RESUMEN
To evaluate the efficacy of the 18F-AlF-NOTA-RGD2 positron emission tomography (PET)/computed tomography (CT) molecular probe for the noninvasive staging of liver fibrosis in mini pigs, a potential alternative to invasive diagnostic methods was revealed. This study used 18F-AlF-NOTA-RGD2 PET/CT imaging of mini pigs to assess liver fibrosis. The methods included synthesis and quality control of the molecular probe, establishment of an animal model of liver fibrosis, blood serum enzymatic tests, histopathological examination, PET/CT imaging, collagen content and expression, and mitochondrial reserve function assessment. The 18F-AlF-NOTA-RGD2 PET/CT molecular probe effectively differentiated various stages of liver fibrosis in mini pigs. Blood serum enzymatic tests revealed distinct stages of liver fibrosis, revealing significant increases in AST, ALT, TBIL, and DBIL levels as fibrosis advanced. Notably, ALT levels increased markedly in severe fibrosis patients. A gradual increase in collagen deposition and increasing α-SMA RNA expression and protein levels effectively differentiated between mild and severe fibrosis stages. Pathological examinations and Sirius Red staining confirmed these findings, highlighting substantial increases in collagen accumulation. PET/CT imaging results aligned with histopathological findings, showing that increased radiotracer uptake correlated with fibrosis severity. Assessments of mitochondrial function revealed a decrease in total liver glutathione content and mitochondrial reserve capacity, especially in patients with severe fibrosis. The 18F-AlF-NOTA-RGD2 PET/CT molecular probe is a promising tool for the noninvasive assessment of liver fibrosis, offering potential benefits over traditional diagnostic methods in hepatology.
RESUMEN
Long-term alcohol overconsumption impairs intestinal and hepatic structure and function, along with dysregulation of zinc homeostasis. We previously found that zinc-glutathione (Zn-GSH) complex effectively suppressed alcohol-induced liver injury in mice. This study was undertaken to test the hypothesis that Zn-GSH suppresses alcohol-induced liver injury by modulating intestinal zinc transporters. Mice were subjected to long-term ethanol feeding, as per the NIAAA model, with groups receiving either an ethanol diet alone or an ethanol diet supplemented with Zn-GSH. Treatment groups were carefully monitored for alcohol consumption and subjected to a final binge drinking exposure. The results showed that Zn-GSH increased the survival rate and decreased the recovery time from binge drinking-induced drunkenness. Histopathological analyses demonstrated a reduction in liver steatosis and the preservation of intestinal integrity by Zn-GSH. It was observed that Zn-GSH prevented the reduction of Zn and GSH levels while increasing alcohol dehydrogenase and aldehyde dehydrogenase in both liver and intestine. Importantly, the expression and protein abundance of zinc transporters ZnT-1, ZIP-1, ZIP-4, ZIP-6, and ZIP-14, all of which are critically involved in intestinal zinc transport and homeostasis, were significantly increased or preserved by Zn-GSH in response to alcohol exposure. This study thus highlights the critical role of Zn-GSH in maintaining intestinal zinc homeostasis by modulating zinc transporters, thereby preventing alcohol-induced intestinal and hepatic injury.