Nephrotoxicity of cyclovirobuxine D in rats

OBJECTIVE To observe the effect of cyclovirobuxine D(CVB-D) on nephrotoxicity in rats and the reversibility of nephrotoxicity.METHODS One hundred and twenty rats were randomly divided into normal control group,CVB-D 2.5,5 and 10 mg·kg-1 groups.Rats in CVB-D groups were ip given CVB-D for 2 months.At the end of first and second month,blood urea nitrogen(BUN),creatinine(SCr),Tamm Horsfall protein(THP) and β2-microglobulin(β2-MG) were detected and N-acetyl-β-D-glucosaminidase(NAG),microalbumin(mAlb),immunoglobulin G(IgG),retinol binding protein(RBP),β2-microglobulin(β2-MG) and transferrin(TRF) in urine were tested while the pathological changes in renal tissue were observed by electron microscope.After the third month,all the indicators for the remaining 10 rats in each group were recorded during the recovery phase.RESULTS Compared with normal control group,after rats were ip given CVB-D for 1 month β2-MG in serum in CVB-D group was significantly increased,but THP levels were sharply reduced in CVB-D 5 and 10 mg·kg-1groups.BUN level increased in CVB-D 10 mg·kg-1 group.NAG,TRF,β2-MG and IgG levels increased in CVB-D 10 mg·kg-1 group,and mAlb and RBP levels in urine increased in CVB-D 5 and 10 mg·kg-1 groups.After rats were given CVB-D for 2 months,compared with normal control group,β2-MG levels in serum in CVB-D 5 and 10 mg·kg-1 groups were significantly increased(P0.05).The BUN level was significantly higher in CVB-D 5 mg·kg-1and THP was significantly lower in CVB-D 10 mg·kg-1group(P0.05).The contents of NAG and IgG in urine rats in CVB-D 10 mg·kg-1 remarkably increased(P0.05,P0.01),also β2-MG and TRF raised significantly(P0.01).Histopathology showed glomerular and tubular necrosis was observed in CVB-D 2.5 mg·kg-1 group and tissue autolysis in CVB-D 5 mg·kg-1 group.In the recovery phase,some serum and urine indicators were higher than those in normal control group.Also,histopathology showed some units within a small amount of renal interstitial infiltration of inflammatory cells or varying degrees of congestion.CONCLUSION CVB-D for long-term use may cause nephrotoxicity,which can not be completely recovered after the drug is suspended.