Decreased ATPase activity in adriamycin nephrosis is independent of proteinuria
In previous studies from this laboratory it has been shown that ATP-ase activity in situ in the glomerular basement membrane (GBM) is clearly reduced in rats rendered nephrotic after treatment with adriamycin (ADR). The question was raised whether this reduction of ATP-ase activity in the GBM is due to toxic activity of ADR or rather a result of the nephrotic condition per se. Therefore, we studied ATP-ase activity using the cerium-based method in kidneys from ADR-treated rats without proteinuria (48 hr after ADR injection), or with proteinuria (approximately 150 mg/24 hr) several weeks after ADR injection. Also kidneys from rats rendered nephrotic by surgical ablation and from non-nephrotic rats treated with local X-irradiation (2000 rads) as well as from normal control rats were studied. The results show that in the GBM of ADR-treated or irradiated rats, clear reduction of ATP-ase activity is observed irrespective of their proteinuria, whereas in the GBM of rats rendered nephrotic by renal ablation (approximately 156 mg/24 hr mean protein excretion) no reduction of enzyme activity is found. It is concluded that decreased ATP-ase activity of the glomerular filtration barrier in ADR-treated rats is due to an early toxic activity of this drug and not a result of the nephrotic state per se. In view of the identical results in X-irradiated rats, it is likely that ADR may act through production of toxic radicals leading to damage of this membrane-associated enzyme system.
- Research Organization:
- Univ. of Groningen, The Netherlands
- OSTI ID:
- 6351926
- Journal Information:
- Kidney Int.; (United States), Vol. 3
- Country of Publication:
- United States
- Language:
- English
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ATP-ASE
ENZYME ACTIVITY
DOXORUBICIN
TOXICITY
KIDNEYS
BIOLOGICAL RADIATION EFFECTS
UROGENITAL SYSTEM DISEASES
PATHOGENESIS
ENDOTHELIUM
EPITHELIUM
NEPHRECTOMY
RATS
X RADIATION
ACID ANHYDRASES
ANIMAL TISSUES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BODY
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
HYDROLASES
IONIZING RADIATIONS
MAMMALS
MEDICINE
ORGANS
PHOSPHOHYDROLASES
RADIATION EFFECTS
RADIATIONS
RODENTS
SURGERY
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VERTEBRATES
560152* - Radiation Effects on Animals- Animals