Protective Effects Of Protocatechuic Acid In Murine Model Of UUO-induced Renal Injury

Chronic kidney disease (CKD) is a global public health problem, affecting millions of people worldwide. CKD can result from obstructive nephropathy; a condition that arises from urinary flow obstruction in the kidneys, leading to renal inflammation and injury. Protocatechuic acid (PCA) is a natural phenolic compound that showed a promising protective effect in cardiovascular diseases. In the current study, we investigated the reno-protective effects of PCA in mice model of unilateral ureteral obstruction (UUO). Male C57BL/6J mice (10-12 weeks old) were divided into 4 groups (n=6-8/group). Sham control, Sham/P (sham plus PCA (50 mg/kg IP daily for two weeks), UUO, and UUO plus PCA. Induction of UUO significantly decreased creatinine clearance (CrCl) and increased pulse wave velocity (PWV), a marker of arterial stiffness, relative to sham control (CrCl; sham control: 60.6 ± 14 vs. UUO: 24.5 ± 6.0 ml/day and PWV; sham control: 1.58 ± 0.1 vs. UUO: 3.35 ± 0.22 m/s). Immuno-histochemical analysis revealed that KIM-1 expression, a marker of tubular injury, was elevated in UUO mice vs. sham control and PCA reduced this elevation, however there was no significance difference in urinary KIM-1 excretion. Moreover, UUO significantly increased renal oxidative stress and inflammation as evidenced by elevation in renal TBARs, IL-6, active caspase-1 and active MMP2 compared to sham control (TBARs; sham control: 8.3 ± 0.9 vs. UUO: 30.5 ± 3.33 nmol/mg protein, renal IL-6; sham control: 1 ± 0.07 vs. UUO: 24.35 ± 8.55 pg/mg protein, active caspase-1; sham control: 1.7 x 10 3 ± 95 vs. UUO: 2.79 x 10 3 ± 145 cpm/μg protein and MMP2; sham control: 1.6 ± 0.4 vs. UUO: 6 ± 0.6 ng/μg protein). PCA treatment significantly improved the UUO-induced decline in creatinine clearance (52.5 ± 10.2 ml/day) and attenuated UUO-induced elevation in renal PWV (1.95 ± 0.1 m/s). Furthermore, PCA treatment significantly decreased renal TBARs (5.2 ± 1.12 nmol/mg protein), IL-6 (5.39 ± 1.4 pg/mg protein) and active MMP2 (1.1 ± 0.3 ng/μg protein) in UUO-induced renal injury. Collectively, these data suggests that PCA provides renal protection in murine model of UUO via reduction of renal oxidative stress, inflammation and fibrosis.