INVOLVEMENT OF INFLAMMATION AND OXIDATIVE STRESS IN THE ADRENOCORTCIAL DYSFUNCTION IN INSULIN RESISTANT RATS: EFFECT OF HEMIN TREATMENT

VECINO, CV; CALDARERI, LILIAN JULIA; WISZNIEWSKI, M; REPETTO, EM; CYMERYNG, CB

Nueva Orleans

Congreso; ENDO 2019 Abstracts - 101st Annual Meeting of the Endocrine Society; 2019

Endocrine Society

The increased consumption ofsweetened beverages has been linked to changes in the prevalence of obesity andinsulin resistance (IR) worldwide. In rats with IR, induced by administrationof a sucrose rich diet, we have previously demonstrated a dysregulation of adrenocorticalsteroid production. As oxidative stress generation and a chronic inflammatorystate have been singled out as hallmarks of this disease, in this study wesought to analyze the effects of HO-1 (an antioxidant enzyme) induction onfunctional parameters in the adrenal cortex. Rats were randomly distributedinto Control (C) and SRD- treated groups. After 12 weeks of treatment, animalsfrom both groups were treated with hemin (15 mg/kg i.p every 48 h; H and SRDHgroups). All animals were sacrificed 2 weeks after and blood and adrenal glandswere excised. Statistical significance of data was analyzed by ANOVA followedby Tukey?s test.Results showed that fastingglucose (p<0.01), triglycerides (p<0.01) and non-esterified fatty acid levels(p<0.05) in serum were increased in both SRD and SRD+H groups compared to Cand H animals. Induction of HO-1 was demonstrated in the adrenal cortex of bothhemin-treated groups (p<0.01 vs.C).Analysis of adrenocorticalmakers of oxidative stress in SRD-treated rats indicates an increase inlipoperoxide levels (p<0.001) while glutathione (p<0.05) and catalase levelswere significantly reduced (p<0.01). These effects were mitigated by hemintreatment.Immunohistochemical studies indicatedan increase in the number of Iba1+ (p<0.01) (monocytederived) cells and higher levels of the inflammasome components ASC and caspase1 in the SRD-group (p<0.001). Interleukin 1β and iNOS protein levels werealso elevated (p<0.05). An increased number of apoptotic cells was alsodetected in the adrenal cortex of SRD-treated rats (TUNEL+) (p<0.05).These effects were not observed in the DRSH group (p<0.01 vs. DRS). Animalsin the SRD group exhibited a lower response in the ACTH stimulation test(p<0.05 vs. C). This effect was not observed in the SRDH group (p<0,001vs DRS). In summary, induction of HO-1 inthe adrenal cortex of SRD-treated rats prevented increases in pro-inflammatorymediators, oxidative stress parameters and in the apoptotic index and restoresthe functional capacity of the adrenal gland upon ACTH stimulation.