- THE NITRONE SPIN TRAP 5,5-DIMETHYL-1-PYRROLINE N-OXIDE REDUCES LIVER NEUTROPHILIC INFLAMMATION IN A MOUSE MODEL OF DIET-INDUCED OBESITY

GUZMAN CF ; CHACON I DEL V; BARRERA FS; RAMÍREZ JM; RIVEROS L, ; MORALES ; BARBIERIS S; SANTILLÁN L; TOLEDO F; DARIO C RAMIREZ; GOMEZ MEJIBA, SANDRA;

san luis

Congreso; SBC; 2024

009 - THE NITRONE SPIN TRAP 5,5-DIMETHYL-1-PYRROLINE N-OXIDE REDUCES LIVERNEUTROPHILIC INFLAMMATION IN A MOUSE MODEL OF DIET-INDUCED OBESITYGuzman CF1, Chacon I del V1, Barrera FS2, Ramírez JM1,2, Riveros L3, Morales I3, Barbieris S3, Santillán L1, Toledo F1, Ramírez DC1, GómezMejiba SE21Laboratory of Experimental and Translational Medicine. 2Laboratory of Nutrition and Experimental Therapeutics.3Laboratory of Bromatology.CONICET-San Luis & National University of San Luis, San Luis, Argentina. E-mail: florguzman56@gmail.comA chronic positive-energy balance causes low-grade systemic inflammation in diet-induced obesity (DIO) models. This causes the activation of theexpression of inflammatory biomarkers, such as inducible nitric oxide synthase (iNOS), inflammatory cytokines, and adhesion molecules forneutrophils in tissue microvasculatures. In this study, our objective was to determine whether the nitrone 5,5-dimethyl-1-pyrroline N-oxide (DMPO)is capable of reducing hepatic neutrophilic inflammation, and systemic inflammation; and consequently improving insulin sensitivity in a DIO mousemodel. To achieve this goal, we fed male C57 mice a control diet (CoD, rodent chow and tap water) or a hypercaloric diet (ObD, 22% bovine fat +10% fructose in drinking water) for 24 weeks. Food and water intake, body weight, and caloric intake were measured weekly. At the end of the dietaryregime, serum IL-6, iNOS, nitrotyrosine formation (a marker of NO-induced oxidative stress), chlorotyrosine (a marker commonly used as a measureof neutrophilic inflammation), and MPO content were assessed by ELISA in liver homogenates. Mice fed the ObD for 24 weeks showed lower foodintake than the CoD group, but higher water with fructose consumption, resulting in a higher total caloric intake, which was reflected in increased bodyweight, and higher epididymal fat content, adiposity index, and insulin resistance (glucose tolerance test). Additionally, ObD mice showed higher IL-6 concentration in serum, suggesting a state of chronic systemic low-grade inflammation and insulin resistance. Mice injected with DMPO (2.5μmol/mice/day for 7 days) or saline, a week before the end of the regimen, showed decreased hepatic inflammation, as well as improved insulinsensitivity, as compared to those mice injected with saline. By blocking the expression of neutrophil adhesion molecules and pro-inflammatorycytokines, DMPO can reduce hepatic neutrophilic inflammation and improve insulin resistance in obesity.