الفهرس 
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Abstract
AKI is a serious medical condition that results in a high morbidity and mortality rates among patients all over the world. Ischemia-reperfusion injury in kidneys is one of the major causes for AKI in hospitalized patients. A plethora of pathophysiologic mechanisms underpins the renal ischemia-reperfusion injury for example hypoxia, inflammation, apoptosis, and oxidative stress. Currently, there is no definitive prophylactic treatment for patients susceptible for RIRI.
Stemming from the aforementioned facts, trying a novel potential prophylactic approach was a very tempting target. Folic acid, which has been used for a long time as a prophylactic agent against prenatal and congenital anomalies, some neurological and hematological disorders, was chosen for the present study to test its possible protective role against RIRI in adult Wistar Albino male rats.
50 rats were used in the experimental design and were randomly allocated into four experimental groups as following:
(1) Sham-operated control group (n=12)
(2) Folic acid-treated group (n=12):
Rats in this group received folic acid (50 mg/kg) orally by gavage, 6 days/ week for 4 weeks, then were subjected to sham renal IR operation.
(3) Renal ischemia-reperfusion group (n=12):
Rats in this group were subjected to 45 minutes of renal ischemia, followed by 48 hours of reperfusion.
(4) Folic acid-treated renal ischemia-reperfusion group (n=14):
Rats in this group received folic acid as group 2 for 4 weeks, then were subjected to renal IR as group 3.
Rats in all studied group were subjected to determination of:
1) Serum levels of urea and creatinine
2) Plasma level of total homocysteine
3) Renal tissue levels of:
• Oxidative stress markers: malondialdehyde (MDA) and superoxide dismutase (SOD) activity.
• Inflammatory markers: nuclear factor-kappa B (NF-κB) and high mobility group box 1 (HMGB1)
• Nitrite
• Mitochondrial function marker: mitochondrial membrane potential (MMP)
• Apoptotic marker: caspase-3
4) Kidney histopathology.
These chosen markers covered different susceptible pathological territories that could be affected by our treatment.
In the present study, renal IR group revealed significant increase in serum levels of creatinine and urea, plasma level of total homocysteine and renal tissue levels of MDA, nitrite, HMGB1, NF-κB, and caspase-3, and significant decrease in renal tissue levels of SOD and MMP. In addition, histopathological examination showed disturbed renal architecture.
Folic acid pretreatment to renal IR group resulted in significant reduction in serum creatinine and urea levels, plasma homocysteine levels and renal tissue levels of MDA, nitrite, HMGB1, NF-κB and caspase-3 and significant increase in renal tissue levels of SOD and MMP. Also, the altered histopathological status was alleviated as manifested by well-preserved glomerulo-tubular cells and brush border and hindrance of the interstitial, and perivascular fibrosis together with attenuation of renal histopathological injury scores.
Therefore, it could be concluded that prophylactic FA treatment exerts a clear renoprotective influence on the present model for AKI through combating different pathophysiological mechanisms triggered by IR, via its antioxidant, anti-inflammatory, and anti-apoptotic effects, NO alleviation and improving mitochondrial function. These folic acid beneficial effects were mediated in part directly and via its Hcy lowering property.