Protective Effects of Levosimendan and N-Acetylcysteine on Remote Liver Injury Associated with Renal Ischemia–Reperfusion in Pediatric Rats

Background and Objectives: Renal ischemia–reperfusion (I/R) injury can cause remote liver injury. This study compared levosimendan and N-acetylcysteine (NAC) against renal I/R-induced kidney dysfunction and remote liver injury in pediatric rats. Materials and Methods: Male Sprague–Dawley rats (postnatal day 25; n = 104) were assigned to Control, Sham, levosimendan (LV), NAC, I/R, I/R+NAC, and I/R+LV groups. Renal I/R was induced by 30 min of right renal pedicle clamping and 24 h of reperfusion; levosimendan (24 µg/kg) or NAC (150 mg/kg) was given intraperitoneally 30 min before ischemia. Serum urea, creatinine, ALT, and AST, renal and hepatic histopathology, and hepatic heat shock and apoptosis-related proteins (Western blotting) were evaluated. Results: Compared with Sham, renal I/R caused tubular injury and significantly increased serum urea, creatinine, ALT, AST, and the hepatic histopathological injury score. Both treatments significantly reduced the serum markers and the hepatic injury score; urea and creatinine did not differ significantly from Sham, whereas transaminases and hepatic injury scores remained elevated. In exploratory Western blot analyses, hepatic Hsp70 was lower in the I/R+LV group than in the I/R group; Hsp90, pro-caspase-3, and cleaved caspase-3 did not differ significantly, and the lower Bax/Bcl-2 ratio with levosimendan was significant only after log transformation. No serum or histopathological parameter differed significantly between the two treatments. Conclusions: NAC and levosimendan both attenuated renal I/R-induced kidney dysfunction and remote liver injury in juvenile rats. Further studies are needed to determine whether this hepatoprotection is direct or secondary to reduced renal injury.