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.
Shimizu
Makiko
M
Department of Clinical Pharmacology and Toxicology, Showa Pharmaceutical University, Tokyo, Japan.
Tatsuno
Masahiro
M
Matsushita
Reiko
R
Totsuka
Junko
J
Inoue
Yuko
Y
Ohta
Kumiko
K
Kuniya
Kensuke
K
Fujii
Naomi
N
Fukasawa
Yoko
Y
Watanabe
Nobuo
N
Iwata
Emiko
E
Miyazaki
Megumi
M
Hoshino
Makiko
M
Onda
Miho
M
Matsumura
Masae
M
Kikuchi
Yuichi
Y
Yamamoto
Chizuru
C
Hamada
Masashi
M
Tsuyuki
Aki
A
Furuta
Takashi
T
Kadokura
Chie
C
Kamiyama
Yoshimi
Y
Kitahara
Goh
G
Suzuki
Kayoko
K
Sejima
Ei
E
Matsumoto
Yoshiaki
Y
Fukuoka
Masamichi
M
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006454:Hemoglobins; D000255:Adenosine Triphosphate; D005978:Glutathione