Effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs

Objective: To investigate the nephrotoxic effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs. Method: Beagle dogs were randomly divided into negative control group( blank tablet),methyl cantharidimide tablets group( 6. 11,12. 21,24. 42 mg·kg-1),continuously 30 days of oral administration,once a day. The drug and control group were collected and determined fresh urine in 1,2,3 and 4 weeks of the administration; Serum urea nitrogen( BUN),creatinine( Crea),total protein( TP) and albumin( ALB) as well as sodium,potassium,chloride electrolyte were determined on 15 and 30 days of the administration; Urine albumin( m Alb),kidney injury molecule-1( KIM-1),neutrophil gelatinase-associated lipocalin( NGAL),N-acetyl-β-D-glucosaminidase( NAG),clusterin,β2-microglobulin( β2-MG),α1-microglobulin( α1-MG),alanine aminopeptidase( AAP) and immunoglobulins Ig G were tested on 15 and 30 days of the administration. Result: Compared with the control group,urine protein and white blood cells was significantly increased in each dose group. On 15 days of the administration,m Alb were higher in each dose group,KIM-1,NGAL,clusterin,NAG and AAP were significantly higher in high-dose group,while the middle and low dose group had no significant difference,as well as blood SCr and BUN no obvious abnormalities. On 30 days,m Alb,KIM-1,clusterin,NAG,AAP were increased in each dose group,appearing dose-effect relationship,β2-MG and NGAL levels were significantly increased in high-dose group. Contents above indicators were increased with significant dose and time relationship,and serum BUN,Scr were correlated,suggesting that urine m Alb,KIM-1,clusterin,NAG and AAP indicators that can sensitively respond the changes of proteins and enzymes in urine. Conclusion: Methyl cantharidimide tablets has a renal toxicity,urine m Alb,KIM-1,clusterin,NAG and AAP can be used as the early nephrotoxic biomarkers of methyl cantharidimide tablets.