Preventive mechanism of protocatechuic aldehyde on cyclophosphamide-induced acute kidney injury via anti-apoptosis
Objective To explore the preventive effect and mechanism of protocatechuic aldehyde(PAL)on acute kidney injury induced by cyclophosphamide(CTX).Methods Twenty-four SPF male KM mice were randomly divided into normal control group,model group,low,high dose PAL group(15,30 mg·kg-1),with six mice in each group.Except for the normal control group and model group,which were given normal saline by gavage,the mice of other groups were given corresponding drugs by gavage once daily.After 14 d,all the mice were given a single intraperitoneal injection of CTX(200 mg·kg-1)except for those of normal control group which were injected with normal saline.On the next day,after weighing and anesthesia,blood and kidneys were obtained.The serum was separated to detect biochemical indicators such as creatinine(CRE),superoxide dismutase(SOD),and catalase(CAT).Hematoxylin eosin(HE)staining was conducted to observe the changes in renal pathological damage.Fluorescence staining was made to detect the expression of TUNEL in mice kidneys.Western blotting was adopted to detect the expression of apoptosis-related proteins such as B-cell lymphoma-2(Bcl-2)and Bcl-2-related X protein(BAX).Results Compared with the control group,the kidney index of the mice in the model group was significantly decreased(P＜0.01).The serum CRE was significantly increased(P＜0.001).The levels of serum SOD,CAT,and GSH-Px were significantly reduced(P＜0.05,0.01,0.001),while the level of MDA was significantly increased(P＜0.01).The kidney cells of the mice in model group were arranged in a disordered manner,with obvious infiltration of inflammatory cells,accompanied by tubular vacuolar degeneration and tubular dilation.The positive expression of TUNEL in the mice kidneys of the model group were significantly increased(P＜0.001).Moreover,the expressions of Caspase-3 and Bcl-2 in the kidneys were significantly decreased(P＜0.01,0.001),while the expressions of cleaved-Caspase-3 and BAX were significantly increased(P＜0.01,0.001).Compared with the model group,the kidney indexes of the mice in PAL-treated groups were significantly increased(P＜0.05).The serum CRE level of the mice in H-PAL-treated group was significantly reduced(P＜0.001).The levels of SOD,CAT,and GSH-Px in the serum of the mice in PAL-treated groups were significantly increased(P＜0.05,0.01,0.001),while the levels of MDA were significantly decreased(P＜0.05).The arrangement of kidney cells in PAL treatment groups was relatively regular,with rare pathological changes such as inflammatory cell infiltration,tubular vacuolar degeneration,and tubular dilation.The positive expression of TUNEL in the kidneys of the PAL treatment groups was decreased(P＜0.01,0.001),the expressions of Caspase-3 and Bcl-2 were obviously increased(P＜0.05,0.01,0.001),and the expressions of cleaved-Caspase-3 and BAX were remarkably decreased(P＜0.01,0.001)in a dose-dependent manner.Conclusion PAL could prevent acute kidney injury caused by CTX,and its mechanism might be related to anti-cell apoptosis.
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