Effects of hemin treatment on hepatic metabolic parameters in a rat model of non-alcoholic fatty liver disease (NAFLD)

CALDARERI L; VECINO C; MORI D; CYMERYNG CB; WISZNIEWSKI, M; PEZZANITI A; REPETTO EM

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia 2019; 2019

Sociedad Argentina de Investigación Clínica

Non-Alcoholic fatty liver disease (NAFLD) isthe most common chronic liver disease. It has been associated withcardiometabolic risk factors. Previous results from our laboratory showed anincrease in oxidative stress parameters in the liver of rats fed a sucrose richdiet (SRD) for 12 weeks. A normalization of these parameters was observed afterthe administration of hemin (15mg/kg ip, every 48hs) for the last two weeks of thedietary modification. Since oxidative stress has been associated with theinduction of tissue damage and/or with metabolic changes in the tissue, in thepresent study we proposed to evaluate the effects of this pharmacologicaltreatment on liver histology and metabolic parameters. Male Wistar rats wererandomly distributed into control (C) and SRD groups (30% sucrose in thedrinking water). Hemin treatment was administered as described (H and SRD+Hgroups). Animals fed a SRD showed lower insulin sensitivity than controls, as assessedby an insulin tolerance test (p<0,0001 vs. C) and the KITT wasnot affected by hemin treatment. Similar results were obtained by analyzing theTAG/HDL-c index, a secondary marker for IR (p<0,0001 vs. C). Hepatic insulinresistance was assessed by a pyruvate tolerance test (PTT). An increasedglucose output was observed in SRD-treated animals (p<0,05 vs. C). Inagreement, protein levels of PEPCK, a gluconeogenic enzyme, were also increasedin this group (p<0,05, vs. C). Hemin treatment corrected both parameters(p<0,05 vs. SRD) The histological analysis showed a higher ballooning scorein the hepatic tissue of animals fed a SRD (p< 0,05 vs. C), and a greater NAFDLactivity score (p<0,05 vs. C). These parameters were not affected by hemintreatment. In summary, hemin treatment of IR-rats is associated with an improvementin insulin sensitivity in the liver, while no changes in systemic insulinresistance and histological parameters associated with tissue damage.