Role of Folic Acid on Ischemia-Reperfusion-Induced Renal Injury in Rats: Folic Acid Prophylactic Effect Revisited

Abstract Background Acute kidney injury (AKI) is a medical condition that has been associated with high morbidity and mortality rates all over the world. Ischemia-reperfusion (IR) has been claimed for AKI incidence especially among hospitalized patients. Unfortunately, there are no definitive preventive measurements or treatment for such a condition stemming from the underpinning complicated pathophysiologic mechanisms. Folic acid has been used for decades as a supplementary nutrient with many positive effects in different pathologies. Aim Our study aims for characterizing the impact of folic acid supplementation on acute kidney injury induced by IR, understanding the molecular mechanisms involved. Materials and Methods The study was conducted on 50 male Wister rats. Experiments were assigned randomly into 4 experimental groups. Group I; Sham-operated control, Group II; FA- treated, Group III; subjected to IR injury, and Group IV: FA- treated and subjected to IR injury. The kidney function was assessed by serum urea and creatinine level, hand in hand with the histopathological analysis. Moreover, plasma total homocysteine (Hcy) level was measured as an independent marker for renal injury. In addition, we measured oxidative stress parameters, inflammatory indicators and apoptotic/ antiapoptotic markers. Results FA pretreatment in renal IR group resulted in a statistically significant reduction in serum creatinine and urea levels, plasma total homocysteine levels and renal tissue levels of malondialdehyde, (MDA), nitrite, high mobility group box-1 (HMGB1), nuclear factor kappa-B (NF-κB) and caspase-3. Meanwhile, FA pretreatment in IR group caused a marked and statistically significant increase in the renal tissue superoxide dismutase (SOD) activity and mitochondrial membrane potential (MMP), when compared to the untreated IR group. The histopathological analysis confirmed the biochemical results underscoring the renoprotective effect of FA. Conclusion Our data show, and for the first time, the beneficial protective impact of FA treatment against renal IR injury, that is associated with subsequent lowering of the renal inflammatory, oxidative stress and apoptotic status. This valuable renoprotective effect of FA could have a positive influence on the trajectory renal function.