Study of the Effect of Aristolochic Acid on Mice Kidney and the Effect of Withdrawal: Histological and Immunohistochemical Study

Abstract

Aristolochic acid (AA), one of the commonly used herbal medicines was reported to cause harmful effect on kidney. In this work, we aimed to study the effect of AA on renal tissue and to investigate the effect of its withdrawal. Methods: Forty five adult male mice were randomly assigned to three groups. Control group, Group 1 where mices were treated with aristolochic acid (AA) i.p. in a dose of 3 mg/kg every 3 days for 6 weeks. In group 2 the (remodeling group), AA was administered i.p. in a dose of 3 mg/kg every 3 days for 6 weeks, followed by 6 weeks remodeling (withdrawal) time. Urine and blood samples were collected; creatinine, BUN and P/C ratio were estimated. Renal specimens were processed for histological examination by H&E, Masson trichrome and immunohistochemical stain for PCNA. Results: in group 1 treated with AA, histological examination revealed that some tubules were atrophied collapsed while others were dilated. Tubular cells exhibited cytoplasmic vacuolation, flattening, necrosis and even shedding. The matrix between tubules was expanded. In the surrounding interstitial areas, mononuclear cell infiltration was observed. Tubulointerstitial cell proliferation was significantly increased as indicated by PCNA immunostaining. This correlates with worsening of renal parameters. However, in group 2, withdrawal of AA led to marked improvement of renal parameters, preservation of renal tissue and reduction of tubular damage and cellular infiltrate. Also, the number of PCNA-positive cells was significantly reduced. In conclusion, aristolochic acid is nephrotoxic and cessation of its administration leads to reduction of this toxicity as was evidenced by laboratory, histological and immunohistochemical methods.