For cerulein-induced acute pancreatitis, male mice (age, 8-10 wk) received 7 hourly intraperitoneal injections of 50 g/kg cerulein in sterile saline. Olanzapine was repeatedly administered orally by gavage at a dose of 5 mg/kg to mice at 3 and 12 hours after the first cerulein injection, while controls were treated by oral administration with vehicle (smooth peanut butter).The parameters of acute pancreatitis were assessed 12 hours after the last cerulein treatment. For the induction of chronic pancreatitis, male mice (age, 8-10 wk) were fed a LieberDeCarli ethanol (5% vol/vol) liquid diet for 4 weeks (F1258; Bio-Serv, Flemington,NJ).In parallel, olanzapine was administered orally by gavage at a dose of 5 mg/kg to mice (3 times per week, over 4 weeks), while controls were treated by oral administration with vehicle. The parameters of chronic pancreatitis were assessed in mice 4 weeks after feeding them the LieberDeCarli ethanol liquid diet.

The 8-weeks old male Sprague-Dawley rats (bodyweight 250-300 g) were purchased from Liaoning changsheng biotechnology co. LTD (Benxi, China). The rats in the taurocholate-induced acute pancreatitis group (Taur, n = 6) were fasted overnight, after anesthesia the hepatic portal of the bile duct was clamped and 3.5% sodium taurocholate (Aladdin, Shanghai, China) in a volume of 1 ml/kg were retrogradely injected into the biliopancreatic duct at a constant speed (0.1 ml/min). The rats in the Sham group (n = 6) were received the laparotomy and the same volume of saline solution. The rats in the disulfiram treatment group (Taur + Disul, n = 6) were administrated with 100 mg/kg pyroptosis antagonist disulfiram (Aladdin) by intraperitoneal (i.p.) injection before the surgery. The rats in the ferrostatin-1 treatment group (Taur + Fer-1, n = 6) were i.p. administered 2.5 mol/kg ferroptosis antagonist ferrostatin-1 (Aladdin) 1 h before the surgery.

For cerulein-induced acute pancreatitis, male mice (age, 8-10 wk) received 7 hourly intraperitoneal injections of 50 g/kg cerulein in sterile saline. Olanzapine was repeatedly administered orally by gavage at a dose of 5 mg/kg to mice at 3 and 12 hours after the first cerulein injection, while controls were treated by oral administration with vehicle (smooth peanut butter).The parameters of acute pancreatitis were assessed 12 hours after the last cerulein treatment. For the induction of chronic pancreatitis, male mice (age, 8-10 wk) were fed a LieberDeCarli ethanol (5% vol/vol) liquid diet for 4 weeks (F1258; Bio-Serv, Flemington,NJ).In parallel, olanzapine was administered orally by gavage at a dose of 5 mg/kg to mice (3 times per week, over 4 weeks), while controls were treated by oral administration with vehicle. The parameters of chronic pancreatitis were assessed in mice 4 weeks after feeding them the LieberDeCarli ethanol liquid diet.

Male C57BL/6 mice (8 weeks old; SPF; weighing 24-26 g, n = 16 in total) were purchased from SPF (Beijing) Biotechnology Co., Ltd. All mice were housed in an environmentally controlled room at a temperature ranging from 20 to 24 on a 12 h light/dark cycle and used in the experiments following an overnight fast with water, availablead libitum. All procedures followed the Principles of Laboratory Animal Care (NIH publication number 85Y23, revised in 1996), and the experimental protocol was approved by the Animal Care Committee, Nanjing Medical University (NMU-2021JK-085).

Male C57BL/6 mice (8 weeks old; SPF; weighing 24-26 g, n = 16 in total) were purchased from SPF (Beijing) Biotechnology Co., Ltd. All mice were housed in an environmentally controlled room at a temperature ranging from 20 to 24 on a 12 h light/dark cycle and used in the experiments following an overnight fast with water, availablead libitum. All procedures followed the Principles of Laboratory Animal Care (NIH publication number 85Y23, revised in 1996), and the experimental protocol was approved by the Animal Care Committee, Nanjing Medical University (NMU-2021JK-085).

Pancreatic-specific gpx4 knockout mice were produced and identified in our laboratory by crossing floxed Gpx4 (a gift from Dr. Qitao Ran, UT Health San Antonio) and Pdx1-Cre (the Jackson Laboratory, 014647) transgenic mice (C57BL/6J background). For cerulein-induced acute pancreatitis, female mice (8-10 weeks) received seven hourly i.p. injections of 50 ug/kg cerulein in sterile saline. We repeatedly administered iHPCAL1 by i.p. at a dose of 10 mg/kg to mice at 3 and 12 h after the first cerulein injection, while controls were treated by administration with vehicle. The parameters of acute pancreatitis were assessed 12 h after the last cerulein treatment.

Pancreatic-specific gpx4 knockout mice were produced and identified in our laboratory by crossing floxed Gpx4 (a gift from Dr. Qitao Ran, UT Health San Antonio) and Pdx1-Cre (the Jackson Laboratory, 014647) transgenic mice (C57BL/6J background). For cerulein-induced acute pancreatitis, female mice (8-10 weeks) received seven hourly i.p. injections of 50 ug/kg cerulein in sterile saline. We repeatedly administered iHPCAL1 by i.p. at a dose of 10 mg/kg to mice at 3 and 12 h after the first cerulein injection, while controls were treated by administration with vehicle. The parameters of acute pancreatitis were assessed 12 h after the last cerulein treatment.