Effects of the Acute and Subacute Administration of 1-(N-methyl) piperazinyl-3-phenyl-isoquinoline on Rat Kidney

  • Lim, Dong-Koo (College of Pharmacy and Institute for drug development Chonnam National University) ;
  • Park, Sun-Hee (College of Pharmacy and Institute for drug development Chonnam National University) ;
  • Noh, Eun-Young (College of Pharmacy and Institute for drug development Chonnam National University) ;
  • Kim, Han-Soo (College of Pharmacy and Institute for drug development Chonnam National University) ;
  • Cho, Won-Jea (College of Pharmacy and Institute for drug development Chonnam National University)
  • 발행 : 2000.03.01

초록

To evaluate the renal toxicity of the antitumor agent, 1-(N-methyl) piperazinyl-3-phenyl-isoquinoline(CWJ-$\alpha$-5), rats were terated with CWJ-$\alpha$-5 (acute : 100mg/kg, i.p., single and subacute : 10mg/kr, i.p., daily for 7 days). The changes in the body weights, water consumption, kidney weights and urine volume after and during the treatment were observed. The concentrations of urinary creatinine, the activities of N-acetyl-$\beta$-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), $\gamma$-glutamyl transpeptidase ($\gamma$-GT) and lactate dehydrogenase (LDH) in 24 hr urine were also determined. The body weight and water consumption were decreased after the acute and subacute administration. However, the excretion of urine was not changed except the 1 day after the acute treatment. The excretion of creatinine was significantly decreased from 1 day after acute administration and continuously decreased. Also the excretion of creatinine was decreased during subacute administration. However, the protein excretion did not changed in both treatment. Those indicate that CWJ-$\alpha$-5 might decrease the metabolic rate of muscle. The urinary activities of NAG, AAP, $\gamma$-GT, and LDH were significantly affected by the drug treatment. The urinary activities of NAG, AAP and $\gamma$-GT were significantly increased 1 and 3 days after the acute administration and then returned to the control value. However, the urinary activities of LDH were increased 7 days after acute treatment. During subacute treatment, the urinary activities of $\gamma$-GT were not changed. However, the urinary activities of NAG, AAP and LDH were only significantly increased after the third administration. These results indicate that either the high acute dose or the subacute administration with low dose of the compound might induce a temporal damage in the kidney cells.

키워드

참고문헌

  1. J. Nat. Prod. v.47 A potential anticancer agents XXXI N-demethylation of fagaronine Arisawa, M.;Pezzuto, J.M.;Bevelle, C.;Cordell, G.
  2. Lactate dehydrogenase. UV-assay with pyruvate and NADH in Methods of Enzymatic analysis Bergmeyer, H.U.;Bernt, E.;Bergmeyer, H.U.(ed.)
  3. Report of Ministry of Health and Welfare Studies of the anticancer agents for new drug development Cheon, S.H.;Cho, W.J.;Chung, B.H.;Lim, D.K.;Chang, S.J.
  4. Jap. J. Pharmacol. v.54 Nephrotoxic indicators in rats Harauchi, T.;Yoshizaki, T.
  5. Arch. Int. Physiol. Biochem. v.89 Diurnal rhythmicity in rat kidney γ-glutamyl transpeptidase activity Hoffman, J.;Hardland, R.
  6. Clin. Chem. Acta v.160 Value of enzyme determination in urine for the diagnosis of nephrotoxicity in rat Hofmeister, R.;Bhagava, A.S.;Gunzel, P.
  7. Clin. Chem. v.2 An optimized assay of alanine aminopeptidase activity in urine Jung, K.;Scholz, D.
  8. Laboratory and diagnostic tests with nursing implications Kee, J.L.
  9. Enzymogta v.37 Enzymes of rat urine: I.A. metabolism cage for the complete separation of urine and faeces Leathwood, P.D.;Plummer, D.T.
  10. Clinical chemistry test Creatine and Creatinine Lee, K.Y.
  11. J. Biol. Chem. v.193 Protein measurement with folin phenol reagent Lowery, O.H.;Rosebrough, N.J.;Farr, A.L.;Randall, R.J.
  12. Clin. Chim. Acta. v.73 Rapid colorimetric assay of β-galactosidase and N-acetyl-β-D-glucosaminidase in human urine Maruhn, D.
  13. J. Toxicol. Sci. v.12 Urinalysis for detection of chemically induced renal damage [1]: Changes in urinary excretion of enzymes and various component caused by mercuric chloride and gentamicin Ohata, H.;Momose, K.;Takahashi, A.;Omori, Y.
  14. J. Cell Biol. v.64 A morphological study of cellular autophagy including diurnal variations in kidncy tubules of normal rat Pfeifer, U.;Scheller, H.
  15. Nitrogen metabolites and renal function in Fundamentals of Clinical Chemistry Rock, R.C.;Walker, W.C.;Jennings, C.D.;Tietz, N.M.(ed.)
  16. Report of NISR Korea v.2 Nephrotoxicity assessment by determination of urinary alanine aminopeptidase in the rat Shin, D.H.;Jang, D.D.;Lee, S.G.;Choi, J.Y.;Cho, J.C.;Hyeon, S.H.
  17. Report of NISR Korea v.3 Nephrotoxicity assessment by determination of urinary enzyme Activities in the rat Shin, D.H.;Jang, D.D.;Lee, S.G.;Choi, J.Y.;Jung, J.Y.;Cho, J.C.;Lee, C.W.;Park, E.B.
  18. γ-Glutarmyl transpeptidase in Methods of Enzymtic Analysis Szasz, G.;Bergmeyer, H.U.(ed.)
  19. Methods in Cancer Research Sufness, M.;Douros, J.;De Vita, V.T.(ed.);Busch, H.(ed.)
  20. Toxicol. Appl. Pharmacol. v.63 Quantification of acute cephaloridine nephrotoxicity in rats: Correlation of serum and 24 hour-urine analysis with proximal tubule injuries Wachsmuth, E.D.