Spironolactone Effect in Hepatic Ischemia/Reperfusion Injury in Wistar Rats

Abstract

Introduction. Ischemia/reperfusion (IR) injury, often associated with liver surgery, is an unresolved problem in the clinical practice. Spironolactone is an antagonist of aldosterone that has shown benefits over IR injury in several tissues, but its effects in hepatic IR are unknown. Objective. To evaluate the effect of spironolactone on IR-induced damage in liver. Materials and Methods. Total hepatic ischemia was induced in rats for 20 min followed by 60 min of reperfusion. Spironolactone was administered and hepatic injury, cytokine production, and oxidative stress were assessed. Results. After IR, increased transaminases levels and widespread acute inflammatory infiltrate, disorganization of hepatic hemorrhage trabeculae, and presence of apoptotic bodies were observed. Administration of SPI reduced biochemical and histological parameters of liver injury. SPI treatment increased IL-6 levels when compared with IR group but did not modify either IL-1β or TNF-α with respect to IR group. Regarding oxidative stress, increased levels of catalase activity were recorded in IR + SPI group in comparison with group without treatment, whereas MDA levels were similar in IR + SPI and IR groups. Conclusions. Spironolactone reduced the liver damage induced by IR, and this was associated with an increase in IL-6 production and catalase activity.

Effects of mineralocorticoid receptor antagonists on responses to hemorrhagic shock in rats

“…Several reports have suggested that MR antagonists modulate the production of cytokines, such as TNF-α, IL-6, and IL-1β, in various organs after IRI[ 9 - 13 ]. Pérez et al[ 10 ] showed that SPL reduces liver damage caused by IRI induced by increases in catalase activity in the liver. Therefore, we hypothesized that pretreatment with MR antagonists has beneficial effects on the expression of genes encoding cytokines, such as TNF-α, IL-6, IL-1β, and ICAM-1, in the liver after recovery from HS.…”

Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model

“…There are a variety of potential modifications of the technique detailed here and some have previously been described in the literature. Depending on the model used molecules have been delivered using inhalation 11 , epidural infusion 12 , intraperitoneal injection 17 18 21 22 , intravenous administration 10 14 15 19 23 24 or injection into the peripheral superior mesenteric vein 8 .…”

“…Variable hilar clamp models have been used by researchers to study the protective effects of anti-oxidants and other small molecules 6 7 8 9 10 11 12 13 14 . Points of variation include which vessels are clamped, which segment are made ischemic, whether or not the bile duct is included and the length of the period of reperfusion 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 . Additionally, when this model is used to study the impact of administration of a molecule the route of administration is also heterogeneous 8 10 11 12 14 15 17 18 19 21 22 23 24 .…”

“…The first is to clamp the portal vein and hepatic artery supplying the left lateral and median lobes, but exclude the bile duct 15 . A second modification is to induce total hepatic ischemia by clamping the portal vein, hepatic artery and bile duct prior to their division 16 17 18 19 20 . A third modification includes clamping of the hilar vessels to the right lobe for 30 to 60 min 8 .…”

Treatment with sodium (S)-2-hydroxyglutarate prevents liver injury in an ischemia-reperfusion model in female Wistar rats

“…As a reference, we considered a previously reported serum activity of ALT of 494 ± 84 U/L for rats subjected to the same IR-injury-induction protocol we used ( Jiménez Pérez et al., 2016 ). We calculated the sample size expecting a 40% decreasing of the serum ALT activity after the treatment (with no change in the standard deviation) and considered a two-tail statistical significance (α) of 0.01 and a statistical power (1−β) of 95%, obtaining a total of 7 rats per group.…”