Protective effects of spironolactone against hepatic ischemia/reperfusion injury in rats

Abstract

Objective: In the present study, it was aimed to study the antioxidant effects of spironolactone (SPL) to determine its possible protective effects in hepatic ischemia reperfusion injury. Material and Methods: Hepatic artery, portal vein, and bile duct of Wistar albino rats were clamped for 45 minutes under anesthesia to form an ischemia period. Then reperfusion was allowed and the rats were decapitated 60 minutes later. SPL (20 mg/kg, p.o.) or SF was orally administered for 30 minutes before ischemia. Rats in the control arm underwent sham surgery and were administered isotonic saline. Liver function was studied by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-α), and interleukin 1beta (IL-1β) levels. Malondialdehyde (MDA), glutathione (GSH), luminol, and lucigenin levels, myeloperoxidase (MPO) and Na +-K +-ATPase enzyme activities were analyzed to study tissue injury under light microscope. Results: While IR increased AST, ALT, TNF-α, and IL-1β levels and MDA, luminol, and lusigenin levels and MPO activities, it caused a decrease in GSH levels and Na + K +-ATPase activity. Spironolactone administration significantly improved these values. Conclusion: Protective effects of SPL against ischemia/reperfusion injury via various mechanisms suggest that this agent may become a novel treatment agent in clinical practice.

Targeting PI3K/p‐Akt/eNOS, Nrf2/HO‐1, and NF‐κB/p53 signaling pathways by angiotensin 1–7 protects against liver injury induced by ischemia–reperfusion in rats

“…The present study demonstrated that there was a significant increase in hepatic immunohistochemical expression of NF‐κB p65 and serum TNF‐α and IL‐6 levels in rats exposed to HIR compared to sham‐operated groups, which is in accordance with Kamel and colleagues, 5,11,33 who reported that ROS produced soon after reperfusion are the key players in inducing activation of NF‐κB. The phosphorylation of NF‐κB triggers the production of TNF‐α and other proinflammatory cytokines, which in turn leads to further liver damage 36 . Moreover Yoon et al 29 mentioned that the inflammatory reactions notably cause tissue damage that results from HIR.…”

“…5,8,[33][34][35] According to Rabie et al, 11 transaminases are reliable markers for estimating the severity of acute liver injury because they are highly expressed in the serum following the damage of liver cells. In addition, Atalay et al 36 pointed out that although there are a number of techniques for evaluating the liver functions in case of IR injury, measuring AST and ALT activities is now considered to be the most popular technique because it is known that the activities of these enzymes increase after hepatic injury. On the other hand, HIR rats pretreated with ang-(1-7) had significantly lower serum levels of AST and ALT than HIR rats.…”

“…The phosphorylation of NF-κB triggers the production of TNF-α and other proinflammatory cytokines, which in turn leads to further liver damage. 36 Moreover Yoon et al 29 mentioned that the inflammatory reactions notably cause tissue damage that results from HIR. One of the main cell types engaged in the inflammatory reactions following HIR injury is the Kupfer cells, which become activated and produce inflammatory cytokines such as TNF-α, IL-1β, and IL-6 when HIR injury first occurs.…”

Antioxidant Activity Of Rat Liver With A Low Resistance To Hypoxia After Systemic Ischemia Reperfusion

“…Such pattern persisted until the end of the experiment, which allowed the aldosterone effects to manifest themselves. That is why, no significant increase in liver enzymes and TNF-α was observed in rats injected with aldosterone antagonists 30 minutes prior to the IRP simulation [17]. Therefore, we conclude that an increase in aldosterone after systemic IRP stimulates liver damage, while its antagonists have hepatoprotective properties.…”

Could Ambroxol reduce cytokines in hepatic ischemia-reperfusion injury in rats?

“…TNF-α directly contributes to liver injury by activating or triggering important infl ammatory factors and increasing neutrophil infi ltration and parenchymal damage. Similarly, IL-1β causes liver cell damage with some effects, such as activating NF-kB, increasing leukocyte aggregation, and upregulating TNF-α production by Kupffer cells (17,25,26). Some studies have reported that Ambroxol reduces the production and release of cytokines (10,11).…”