Naringin avoids the hepatic mitochondrial dysfunction caused by the experimental type 1 diabetes

GUIZZARDI S; PEREZ A; RODRÍGUEZ V; TOLOSA DE TALAMONI N

Mar del Plata

Congreso; Reunión Anual SAIC-SAI-SAFIS; 2020

In a previous work we have shown that naringin (NAR), a natural flavonoid, protects against the liver damage caused by STZ (streptozotocin)-induced diabetes. The aim of this study was to determine whether NAR modifies the redox state of liver mitochondria altering the Krebs cycle function, which could lead to perturbations in the mitochondrial dynamics and biogenesis. Male Wistar rats were divided into three groups: 1) controls, 2) STZ rats (diabetes induced by 60 mg/kg b.w. STZ), 3) STZ rats treated daily with NAR (40 mg/kg b.w.) for 30 days. Rat liver mitochondria were isolated from the different groups of animals. Oxidative stress parameters, activities of Krebs cycle enzymes and ATP synthase as well as mitochondrial dynamics and biogenesis markers were determined. Results were evaluated by ANOVA and Bonferroni test. STZ rats showed decreased isocitrate dehydrogenase (ICDH) and malate dehydrogenase (MDH) activities affecting ATP synthesis. NAR completely blocked these alterations. STZ rats also presented hepatic mitochondrial oxidative stress, as indicated by a lower GSH level and higher superoxide anion and protein carbonyl contents and catalase activity. NAR administration avoided these changes. STZ rats decreased the gene expression of Drp-1 and Mfn-2, two molecules involved in the mitochondrial dynamics, an effect that was blocked by NAR. The gene expression of Pgc1-α and Tfam, two molecules involved in the mitochondrial biogenesis, remained unchanged in all groups. In conclusion, the experimental diabetes produces oxidative stress, decrease in the activity of enzymes from the Krebs cycle and ATP synthase and alteration in the mitochondrial dynamics. NAR protects the liver mitochondria against the dysfunction produced by STZ-induced diabetes.