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.

Figure 1

Dose-response study of spironolactone on hepatic injury in total normothermic IR. The effects of SPI treatment on ALT and AST levels were assessed. Rats were treated with SPI (0, 1,000, 2,600, 5,000, 10,000, and 20,000 μg/kg). Transaminase levels were measured after 1 h of reperfusion. Means without a common letter are different; P < 0.05.

Figure 2

Effect of spironolactone on biochemical parameters of liver injury in total normothermic IR. ALT and AST levels were measured in plasma. ^∗ P < 0.05 versus Sham; ⁺ P < 0.05 versus IR.

Figure 3

Hematoxylin and eosin staining of hepatic tissue. The Sham group (a) showed conserved cellular architecture. IR group (b) showed numerous inflammatory cell groups predominantly perivenular and presence of apoptotic bodies isolated surrounded by inflammation. The IR + SPI group (c) showed conserved cellular architecture, isolated pockets of acute inflammation, and apoptotic bodies.

Figure 4

Effect of spironolactone on biochemical parameters of liver injury in normothermic PIR. ALT and AST levels were measured in plasma. ^∗ P < 0.05 versus Sham; ⁺ P < 0.05 versus PIR.

Figure 5

Effect of spironolactone on cytokine production in normothermic IR injury. IL-1β, IL-6, and TNF-α levels were measured in plasma. ^∗ P < 0.05 versus Sham; ⁺ P < 0.05 versus IR.

Figure 6

Effect of spironolactone on oxidative stress in normothermic IR injury. Total antioxidant capacity, catalase activity, and MDA levels were measured in plasma. ^∗ P < 0.05 versus Sham; ⁺ P < 0.05 versus IR.