Fig. 3: Navitoclax and Venetoclax in cerulein- and EtOH/POA-induced models of AP.

A Representative hematoxylin and eosin (H&E) stained images of mouse pancreata from the cerulein-induced AP model. Both Navitoclax and Venetoclax significantly reduced tissue injury and edema. Scale bar: 100 µm. Images taken with a 20 × magnification objective. B Heatmap displaying the histological evaluation scores of pancreata from the cerulein-induced AP model. Evaluated parameters included edema (Edm, 0/1/2/3), inflammatory infiltration (Infltr, 0/1/2/3), fat necrosis (FNec, 0/3/5/7), parenchymal necrosis (PNec, 0/3/5/7), and hemorrhages (Hem, 0/3/5/7) [20]. C Overall histological severity score (0−27) for each group in the cerulein-induced AP model, derived from the average assessments of two blinded investigators. Results are presented as mean ± SD. D Representative H&E stained images of mouse pancreata from the EtOH/POA-induced AP model. Application of Navitoclax and Venetoclax resulted in markedly reduced tissue injury and edema. Scale bar: 100 µm. E Heatmap depicting the histological evaluation scores of pancreata from the EtOH/POA-induced AP model. Scores for edema (Edm, 0/1/2/3), inflammatory infiltration (Infltr, 0/1/2/3), fat necrosis (FNec, 0/3/5/7), parenchymal necrosis (PNec, 0/3/5/7), and hemorrhages (Hem, 0/3/5/7) are presented, similar to B [20]. F Overall histological severity score (0−27) for each group in the EtOH/POA-induced AP model, calculated from blinded assessments by two independent investigators. Results are presented as mean ± SD. G Representative immunohistochemical staining images of cleaved caspase-3 in pancreata from the cerulein-induced AP model, indicating apoptosis. Scale bar: 50 µm. H-I Quantification of apoptotic cells per mm² in the cerulein-induced AP model, determined through immunohistochemical staining for cleaved caspase-3. Analyses were performed on whole tissue sections and results are presented as mean ± SD. The graphs show the same values for Sham and AP. J Percentage of necrotic areas in mouse pancreata from the cerulein AP model. Results are presented as mean ± SD. K Platelet counts from postmortem blood samples of mice from the cerulein AP model, analyzed using the ABC VET hematology analyzer. Results presented as mean ± SD. L Representative images of immunohistochemical staining of cleaved caspase-3 in pancreata from the EtOH/POA-induced AP model, indicating apoptosis. Scale bar: 50 µm. Images captured with a 40 × magnification objective. M, N Quantification of apoptotic cells per mm² in the EtOH/POA-induced AP model, analyzed on whole tissue sections and results presented as mean ± SD. The graphs show the same values for Sham and AP. O Percentage of necrotic areas in mouse pancreata from the EtOH/POA-induced AP model. Results presented as mean ± SD. P Platelet counts from postmortem blood samples of mice from the EtOH/POA-induced AP model, analyzed using the ABC VET hematology analyzer. Results presented as mean ± SD. Statistical analyses: For the cerulein-induced AP model, n = 6 for all groups; for the EtOH/POA-induced AP model, n = 5, except for the AP Navi group with n = 4. The statistical analyses were performed using the non-parametric Kruskal-Wallis test followed by Dunn’s post hoc test, applied due to some datasets not being normally distributed or when n < 6. Figure Abbreviation Legend: Sham (saline + vehicle), Navi (saline + Navitoclax), Ven (saline + Venetoclax), AP (cerulein or EtOH/POA + vehicle), AP + Navi (cerulein or EtOH/POA + Navitoclax), AP + Ven (cerulein or EtOH/POA + Venetoclax).