title: Correlation between the physicochemical property of some nonsteroidal anti-inflammatory drugs and changes in adenosine triphosphate, glutathione and hemoglobin in rat erythrocytes.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Showa Pharmaceutical University, Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tatsuno
authors.forename: Reiko
authors.initials: R
authors.lastname: Matsushita
authors.forename: Junko
authors.initials: J
authors.lastname: Totsuka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Inoue
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ohta
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kuniya
authors.forename: Naomi
authors.initials: N
authors.lastname: Fujii
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fukasawa
authors.forename: Nobuo
authors.initials: N
authors.lastname: Watanabe
authors.forename: Emiko
authors.initials: E
authors.lastname: Iwata
authors.forename: Megumi
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Makiko
authors.initials: M
authors.lastname: Hoshino
authors.forename: Miho
authors.initials: M
authors.lastname: Onda
authors.forename: Masae
authors.initials: M
authors.lastname: Matsumura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Chizuru
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Hamada
authors.forename: Aki
authors.initials: A
authors.lastname: Tsuyuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Furuta
authors.forename: Chie
authors.initials: C
authors.lastname: Kadokura
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kamiyama
authors.forename: Goh
authors.initials: G
authors.lastname: Kitahara
authors.forename: Kayoko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Ei
authors.initials: E
authors.lastname: Sejima
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Masamichi
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000097:blood*; D006454:Hemoglobins / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006454:Hemoglobins; D000255:Adenosine Triphosphate; D005978:Glutathione