3-aminobenzamide protects against colitis associated diabetes mellitus in male BALB/c mice: Role of PARP-1, NLRP3, SIRT-1, AMPK

Diabetes and ulcerative colitis are chronic diseases associated with inflammation, dysbiosis, impaired immune function and infection risk. In patients with type 1 diabetes enteropathy, gastrointestinal manifestations are seen relatively frequently. The current investigation was aimed to decipher the role of 3-aminobenzamide (3-AB) in ulcerative colitis associated Diabetes mellitus in male BALB/c mice. Ul-cerative colitis associated Diabetes mellitus experimental murine model was developed by 3 cycles (each cycle consists of seven days) of Dextran Sulphate Sodium (DSS; 2.5 %w/v) with recovery time of one week in-between along with Streptozotocin (STZ; 40 mg/kg; i.p. x 5 days; consecutively) was given at the Ist recovery period. As an intervention, 3-aminobenzamide (3-AB; 5 and 10 mg/kg; intraperitoneally) was given beginning with the second DSS cycle and then continue till sacrifice. 3-aminobenzamide treatment significantly reduced the severity of colitis-associated diabetes mellitus by altering the expression of a number of molecular targets, including sirtuin 1 (SIRT 1), proliferating cell nuclear antigen (PCNA), poly [ADP-ribose] polymerase 1 (PARP-1), cysteine protease-1 (Caspase-1), nuclear factor kappa-light-chain -enhancer of activated B cells (NFkBp65), NLR family pyrin domain containing 3 (NLRP3), insulin growth factor 1 (IGF-1), interleukin-1(3 (IL-1(3), interleukin-10 (IL-10) and (3-catenin. Further, 3-AB at high dose (10 mg/kg; intraperitoneally) significantly restored the epithelial tight junction integrity as evaluated by TEM analysis and restored occludin expression analysed by immunofluorescence analysis. Present study revealed that the high dose of 3-AB (10 mg/kg; intraperitoneally) showed significant and consistent protective effects against colitis associated Diabetes mellitus by modulating various molecular targets.(c) 2023 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

Automated summary

Diabetes and ulcerative colitis are chronic diseases associated with inflammation, dysbiosis, impaired immune function, and infection risk. This study aimed to investigate the role of 3-aminobenzamide (3-AB) in ulcerative colitis-associated diabetes mellitus. The results showed that 3-AB significantly reduced the severity of colitis-associated diabetes mellitus by altering the expression of multiple molecular targets.