Hemin treatment improves glucocorticoid response to experimental sepsis in diet-induced insulin resistant rats

CALDARERI, LILIAN; MEISNER, FRANCO; WISZNIEWSKI, MORENA; MARTINEZ CALEJMAN, C; REPETTO, EM; CYMERYNG, CORA B

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Sociedad Argentina de Investigación Clínica

An exacerbatedresponse to infection, resulting in systemic inflammation, is observed duringsepsis. Under these conditions, an ad- equate production of glucocorticoids iscritical since they prevent an excessive and unbalanced immune response and forits effects on the cardiovascular system and metabolism. We have previously demonstratedthe onset of adrenocortical insufficiency in rats made insulin resistant by theadministration of a sucrose rich diet (SRD). An increase in oxidative stressand inflammation parameters were detected in the adrenal cortex of SRD-treatedrats. The goal of the present study was to evaluate the production of GCs inSRD-treated rats in a model of sepsis by cecal ligation and puncture (CLP) andto assess the effects of hemin treatment, an inductor of an antioxidant andanti-inflammatory response, on the adrenal function. Adult male Wistar ratswere fed a standard diet (controls, C) or a SRD, and then treated with/withouthemin (SRDH, 15 mg/kg every 48 hours) for the last 2 weeks before surgery. Atthe end of the 12th week rats underwent CLP and were sacrificed 24 or 72 hourslater (survival curve). Hormone determinations and RT-PCR were performed. Ourresults show higher plasma ACTH levels in the SRD-group 24 h after CLP(p<0.05 vs. C). These animals exhibited a diminished response to exogenousACTH (p<0.01 vs. C), an effect that was not observed in the DRSH group. Asignificant increase in StAR protein levels was also observed in DRSH treatedrats (p<0.01 vs. DRS). Lower serum corticosterone levels were detected 72 hafter CLP in DRS-treated rats (p<0.01 vs. C or DRSH). The rate of survivalto sepsis was higher in SRDH group (p<0.05 vs. DRS). In summary, administrationof a SRD for several weeks affects the steroidogenic function of the adrenalcortex. Hemin treatment appears to prevent this adrenal dysfunction observed inDRS treated rats in sepsis and improves its survival rate.