Effects of thymic hormone on reactive oxygen species-scavengers and renal function in tacrolimus-induced nephrotoxicity.
The effects of a thymic hormone (Facteur thymique serique; FTS) on renal reactive oxygen species-scavenging enzymes or substances in heminephrectomized rats with and without tacrolimus-induced nephrotoxicity were studied. Rats received both oral dose of tacrolimus (5 mg/kg/day) and subcutaneous administration of three dosages of FTS (5, 50, and 250 microg/kg/day) over 28 days (Group A). In Group B, they received three dosages of FTS alone (0.5, 5, and 50 microg/kg/day) or FTS 50 microg/kg/day with tacrolimus over 28 days. Each dose of FTS (Group A) partially elevated renal creatinine clearances. Tacrolimus enhanced renal glutathione reductase (GSH-R) activities and glutathione (GSH) and depressed catalase (CAT) activities. FTS increased GSH levels and GSH-R activities. Although FTS alone did not change CAT activities, CAT activities recovered as a result of concomitant use of FTS (Groups A and B). A significant positive correlation was found between CAT activity and creatinine clearance. These findings suggest that FTS is useful for the prevention of tacrolimus-induced nephrotoxicity, and that the increase of renal CAT activity in the defense mechanism of FTS might be important for cell protection against active oxygen species.
Tada
Hitoshi
H
Department of Pharmaceutical Science, Akita University Hospital, Hondo, Japan.
Nakashima
Atsuko
A
Awaya
Akira
A
Fujisaki
Akiko
A
Inoue
Kazuyuki
K
Kawamura
Koichi
K
Itoh
Kunihiko
K
Masuda
Hirotake
H
Suzuki
Toshio
T
D000818:Animals; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000378:metabolism; D006086:Graft vs Host Disease / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D016559:Tacrolimus / Q000633:toxicity*; D013935:Thymic Factor, Circulating / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; D013935:Thymic Factor, Circulating; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D016559:Tacrolimus