Effect of RGZ on adipokine levels in mice with AP.

<p>Mice in the LFD (green columns), LFD + RGZ (orange columns), HFD (blue columns) or HFD + RGZ (pink columns) groups received two injections of IL-12+ IL-18 and were evaluated at Day 1 and Day 7. Control mice received vehicle. Circulating levels of leptin (<b>A</b>) and adiponectin (APN) (<b>B</b>) were measured by ELISA. Data are mean +/− SEM of 8–12 mice per group.</p

Effect of RGZ on hematological parameters in mice with AP.

<p>Mice received two injections of IL -12+ IL-18 and were evaluated at Day 1 and Day 7. Control mice received vehicle. Circulating while blood cells (WBC) (<b>A</b>), % neutrophils (<b>B</b>), % lymphocytes (<b>C</b>) and % monocytes (<b>D</b>) as well as red blood cells (RBC) (<b>E</b> absolute value, <b>F</b> % change from baseline), concentration of hemoglobin (<b>G</b> absolute value, <b>H</b> % change from baseline), and hematocrit (<b>I</b> absolute value, <b>I</b> % change from baseline) were quantified in blood obtained from LFD (green columns), LFD + RGZ (orange columns), HFD (blue columns) or HFD + RGZ (pink columns) groups. Data are mean +/− SEM of 8–12 mice per group.</p

Experimental design.

<p>Timing of LFD and HFD feeding with and without RGZ, administration of vehicle or IL-12+ IL-18 (2 injections, 24 h apart), and termination of the experiment is shown.</p

Effect of RGZ on the pancreatic inflammatory infiltrate.

<p>Mice received two injections of IL -12+ IL-18 and were evaluated at Day 1 and Day 7. Control mice received vehicle. Infiltration by neutrophils (<b>A</b>), macrophages (<b>B</b>) and lymphocytes (<b>C</b>) was quantified by a pathologist in sections of pancreas obtained from LFD (green columns), LFD + RGZ (orange columns), HFD (blue columns) or HFD + RGZ (pink columns) groups. Data are mean +/− SEM of 8–12 mice per group.</p

Effect of RGZ on AP induced by IL-12+ IL-18.

<p>Mice in the LFD (green columns), LFD + RGZ (orange columns), HFD (blue columns) or HFD + RGZ (pink columns) groups received two injections of IL-12+ IL-18 and were evaluated at Day 1 and Day 7. Control mice received vehicle. <b>R</b>epresentative H&E staining of sections of the pancreas as shown in Panel A. Histological scores for pancreatic acinar necrosis (<b>B</b>), fat necrosis (<b>C</b>), inflammatory infiltrate (<b>D</b>) and edema (<b>E</b>) as well as VAT saponification (<b>F)</b> were calculated as described in the Methods section. Levels of amylase (<b>G</b>) and IFN-gamma (<b>H</b>) were measured in plasma. Data are mean +/− SEM of 8–12 mice per group.</p

Effect of RGZ in control mice.

<p>Body and pancreas weight, % fat mass, average daily food intake during the last week of feeding with the various diets, plasma levels of leptin, adiponectin, glucose, insulin, triglycerides (TG) and amylase, were measured in LFD and HFD groups with or without RGZ. Data are mean +/− SEM of 6–8 mice per group.</p>a<p>p<0.001 <i>vs.</i> LFD groups;</p>b<p>p<0.05,</p>c<p>p<0.001 <i>vs.</i> respective group without RGZ by ANOVA.</p

Effect of RGZ on survival from AP in LFD and HFD mice.

<p>Mice in the LFD (green line), LFD + RGZ (orange line), HFD (blue line) or HFD + RGZ (pink line) received two injections of IL-12+ IL-18 at 150 and 750 ng/mouse each, respectively and survival monitored for 15 days. No further lethality was observed after Day 7. Data are from 10–15 mice per group.</p

Effect of RGZ on pancreatic and circulating inflammatory mediators.

<p>Mice received two injections of IL -12+ IL-18 and were evaluated at Day 1 and Day 7. Control mice received vehicle. Levels of by IL-6 (<b>A–B</b>), osteopontin (OPN) (<b>C–D</b>), TIMP1 (<b>E–F</b>) and Galectin-3 (Gal3) (<b>G–H</b>) were quantified in pancreatic homogenates (<b>A, C, E, G</b>) and plasma (<b>B, D, F, H</b>) obtained from LFD (green columns), LFD + RGZ (orange columns), HFD (blue columns) or HFD + RGZ (pink columns) groups. Data are mean +/− SEM of 8–12 mice per group.</p

Effect of RGZ on hematological parameters in control mice.

<p>White blood cell (WBC) counts, Neutrophil (NE), Lymphocyte (LY), Monocyte (MO), Eosinophil (EO) and Basophil (BA) absolute numbers and percentages, Red Blood cell (RBC) numbers, Hemoglobin (Hgb) levels, Hematocrit (Hct), Mean corpuscolar volume (MCV), Mean corpuscolar hemoglobin (MCH), platelet number and Mean Platelet Volume (MPV) were evaluated on EDTA-anticoagulated peripheral blood using a Hemavet 950FS. Data are mean +/− SEM of 6–8 mice per group.</p>a<p>p<0.05 vs. each other group;</p>b<p>p<0.001 vs. respective group without RGZ by ANOVA.</p