Anti-inflammatory Effects of Valproic Acid in a Rat Model of Renal Ischemia/Reperfusion Injury: Alteration in Cytokine Profile

Abstract

Valporic acid (VPA) has been implicated to have anti-inflammatory and anti-oxidant activities in several ischemic/reperfusion (I/R) injury models. This study intended to evaluate whether VPA could affect the inflammatory/anti-inflammatory cytokines balance and severity of renal I/R injury in rat. I/R injury was induced in two groups of animals, vehicle normal saline and VPA-treated (IP injection, 150 mg/kg) rats, by 45 min occlusion of both left and right renal arteries followed by 3, 24 and 120 h reperfusion in separate groups. After each time point, kidneys and blood samples were collected for cytokine genes (TNF-α, IL-1β, IL-10 and TGF-β) expression analysis and histological examinations in the kidney tissues. Serum creatinine levels were measured for evaluation of renal function. We observed significantly downregulated mRNA expressions for IL-1β and TNF-α in blood and tissue samples 24 and 120 h post I/R injury in VPA-treated animals compared to control groups (P < 0.0001). On the other hand, mRNA expression levels for IL-10 and TGF-β were significantly increased in the blood samples from VPA-treated animals at two time points after I/R injury (P < 0.0001) and at 120 h in tissue samples (P < 0.001). Histopathology analysis showed downgraded ischemic changes in VPA group compared to sham control. Also, decreased serum creatinine levels were observed in VPA-treated animals particularly 120 h post I/R injury (P < 0.0001) that was correlated with less pathological changes in this group. Our results indicate that VPA can attenuate pro-inflammatory responses and augment the anti-inflammatory condition in favor of faster renal recovery from ischemic changes and improved renal function after renal I/R injury.

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