Long-term effects of a novel phosphorothionate (RPR-II) on detoxifying enzymes in brain, lung, and kidney rats.
The effects of a phosphorothionate, 2-butenoic acid-3-(diethoxyphosphinothioyl) methyl ester (RPR-II), on the activities of glutathione S-transferase (GST) and UDP-glucuronyltransferase (UDPGT) and the level of glutathione (GSH) were evaluated in rats after administration of RPR-II at 0.014 (low), 0.028 (medium), and 0.042 (high) mgkg(-1)day(-1) for 90 days and also at 28 days (withdrawal) after stopping treatment. Brain GST activity and GSH level decreased significantly at the high dose on the 45th and 90th days of treatment. Dose- and time-dependent decreases in GST activity and GSH was level were observed in lung at medium and high doses and in kidneys at all three doses on both the 45th and 90th days. UDPGT activity increased significantly in kidneys at the medium and high doses at 45 and 90 days. Brain and lung did not display any significant variations in UDPGT activity when compared with the control. Interestingly, the withdrawal study revealed that the effect was reversible within 28 days of cessation of treatment, when enzyme activity reverted to levels close to those of controls. The study revealed that RPR-II affected the GSH- and GST-dependent detoxification system of the treated tissues of rat and its potential to modulate the enzymes is in the order kidneys>lung>>brain. The present subacute study suggests that RPR-II may bring about physiological upsets by altering GSH- and GST-dependent events in different tissues of exposed organisms.
Mahboob
M
M
Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India. mahboob@iict.ap.nic.in
Siddiqui
M K J
MK
D000818:Animals; D001921:Brain / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis* / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D008168:Lung / Q000201:enzymology*; D008297:Male; D008999:Monocrotophos / Q000009:adverse effects* / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000009:adverse effects*; D014018:Tissue Distribution
D013438:Sulfhydryl Compounds; C066789:RPR 2; D008999:Monocrotophos; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D005978:Glutathione