Correlation between the physicochemical property of some nonsteroidal anti-inflammatory drugs and changes in adenosine triphosphate, glutathione and hemoglobin in rat erythrocytes.

This study was conducted to explore the relationship between physicochemical property and toxic effectiveness using rat red blood cells (RBCs). The toxic effectiveness of acid nonsteroidal anti-inflammatory drugs (NSAIDs) was systemically examined by the depletion of intracorpuscular adenosine triphosphate (ATP), glutathione (GSH), and hemoglobin (Hb) at various doses, increased every 5 fmol/RBC. When the RBCs were incubated with NSAIDs, the drugs attained maximum levels within RBC, and the levels were then reduced. The ATP depletion seemed to be observed on the excretion of the drugs prior to the depletions of GSH and Hb. The physicochemical properties of NSAIDs were obtained from QMPRPlus, SMILES code, and CS ChemRaw Ultra. Correlation between their physicochemical properties and their doses for the depletions of ATP, GSH and Hb was performed in comparison with those of the membrane bound enzyme (MBE) inhibiting- and methemoglobin (MHb)-generating drugs. The ATP depletion by NSAIDs was correlated with the GSH depletion and intracorpuscular levels of the drugs, but not with the Hb depletion. The GSH depletion was correlated with the Hb depletion and participated in the lipophilicity of the drugs.

[1]  J. Fagan,et al.  The ATP-independent pathway in red blood cells that degrades oxidant-damaged hemoglobin. , 1992, The Journal of biological chemistry.

[2]  K. Eckert The metabolism of aminophenols in erythrocytes. , 1988, Xenobiotica; the fate of foreign compounds in biological systems.

[3]  P. Eder,et al.  Phosphorylation reduces the affinity of protein 4.1 for spectrin. , 1986, Biochemistry.

[4]  T. Karasawa,et al.  Inhibitory effect of zonisamide on human carbonic anhydrase in vitro. , 1993, Arzneimittel-Forschung.

[5]  R. Sik,et al.  The Effect of Static Magnetic Fields on the Photohemolysis of Human Erythrocytes by Ketoprofen , 1998, Photochemistry and photobiology.

[6]  J. Bond,et al.  Glucose intolerance following cis-platinum treatment in rats. , 1982, Toxicology.

[7]  L. Beck,et al.  Fluorometric estimation of GSH-OPT. , 1968, Analytical biochemistry.

[8]  G. Sahin,et al.  In vitro effects of NSAIDS and paracetamol on oxidative stress-related parameters of human erythrocytes. , 2001, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[9]  C. Haest,et al.  Evidence for a role of the multidrug resistance protein (MRP) in the outward translocation of NBD-phospholipids in the erythrocyte membrane. , 1998, Biochimica et biophysica acta.

[10]  C. Poyart,et al.  Organic phosphates modulate anion self-exchange across the human erythrocyte membrane. , 1984, Biochimica et biophysica acta.

[11]  O. Sabzevari,et al.  Idiosyncratic NSAID drug induced oxidative stress. , 2002, Chemico-biological interactions.

[12]  B. Eberlein-König,et al.  Phototoxicity of non-steroidal anti-inflammatory drugs: in vitro studies with visible light. , 1996, Acta dermato-venereologica.

[13]  M. Fama,et al.  MOLECULAR MECHANISM OF DRUG PHOTOSENSITIZATION–II. PHOTOHEMOLYSIS SENSITIZED BY KETOPROFEN , 1989, Photochemistry and photobiology.

[14]  M. Gladwin,et al.  Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. , 2002 .

[15]  P. Eyer Detoxication of N-oxygenated arylamines in erythrocytes. An overview. , 1988, Xenobiotica; the fate of foreign compounds in biological systems.

[16]  Homberg Jc [Drug-induced autoimmune hemolytic anemia]. , 1999 .

[17]  M. Büyükokuroğlu,et al.  In vitro effects of some anesthetic drugs on enzymatic activity of human red blood cell glucose 6-phosphate dehydrogenase. , 2002, Polish journal of pharmacology.

[18]  E. Ling,et al.  Modulation of red cell band 4.1 function by cAMP-dependent kinase and protein kinase C phosphorylation. , 1988, The Journal of biological chemistry.

[19]  A. Goldberg,et al.  Red blood cells contain a pathway for the degradation of oxidant-damaged hemoglobin that does not require ATP or ubiquitin. , 1986, The Journal of biological chemistry.

[20]  M. Comporti,et al.  Iron release, lipid peroxidation, and morphological alterations of erythrocytes exposed to acrolein and phenylhydrazine. , 1994, Experimental and molecular pathology.

[21]  M. Shimizu,et al.  Effects of aspirin and/or salicylate on hydrolysis and glucuronidation of indomethacin in rat erythrocytes and hepatocytes. , 2003, Biological & pharmaceutical bulletin.

[22]  A. Hayes Principles and methods of toxicology , 1982 .

[23]  J. Belli,et al.  Changes in intra- or extracellular pH do not mediate P-glycoprotein-dependent multidrug resistance. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Marcia Sanford-Driscoll,et al.  Induction of Hemolytic Anemia by Nonsteroidal Antiinflammatory Drugs , 1986, Drug intelligence & clinical pharmacy.

[25]  C. Saldanha,et al.  Red blood cell membrane integrity in primary open angle glaucoma: ex vivo and in vitro studies , 1999, Eye.

[26]  A. Zbehlik,et al.  Benzocaine-Induced Methemoglobinemia: Report of a Severe Reaction and Review of the Literature , 1994, The Annals of pharmacotherapy.

[27]  P. Rouger,et al.  Anémie hémolytique induite par les médicaments , 2001 .

[28]  B. Eberlein-König,et al.  Interaction of ultraviolet‐B‐rich and ultraviolet‐A‐rich radiation in ketoprofen‐induced photohemolysis , 1996, Photodermatology, photoimmunology & photomedicine.

[29]  M. Comporti,et al.  Iron release and membrane damage in erythrocytes exposed to oxidizing agents, phenylhydrazine, divicine and isouramil. , 1992, The Biochemical journal.

[30]  B. K. Park,et al.  The use of a three compartment in vitro model to investigate the role of hepatic drug metabolism in drug-induced blood dyscrasias. , 1993, British journal of clinical pharmacology.

[31]  M. Rendell,et al.  Red cell filterability determined using the cell transit time analyzer (CTTA): effects of ATP depletion and changes in calcium concentration. , 1992, Biochimica et biophysica acta.

[32]  V. H. Cohn,et al.  A fluorometric assay for glutathione. , 1966, Analytical biochemistry.

[33]  P. Boivin Role of the phosphorylation of red blood cell membrane proteins. , 1988, The Biochemical journal.

[34]  P. Kintz,et al.  Simultaneous HPLC analysis of the hypnotic benzodiazepines nitrazepam, estazolam, flunitrazepam, and triazolam in plasma. , 1991, Journal of analytical toxicology.

[35]  H. Miyazaki,et al.  Binding of sulfonamides to erythrocytes and their components. , 1989, Chemical & pharmaceutical bulletin.