Regulation of total ovarian glutathione content in the rat.
Glutathione (GSH) is an important intracellular thiol capable of altering metabolism following exposure to certain important biologic toxicants including radiation and cyclophosphamide. In order to evaluate the inhibition of glutathione synthesis in the ovary, 30-day-old Sprague Dawley rats were treated with either saline or 0.6 mumol/kg (0.133 mg/kg), 6.0 mumol/kg (1.33 mg/kg), or 4.5 mmol/kg (1000 mg/kg) buthionine sulphoximine (BSO) IP and sacrificed at 0, 1, 2, 4, 6, 8, and 24 h. There was an inhibition of glutathione synthesis with 4.5 mmol/kg (1000 mg/kg) BSO with a nadir at 8 h (P less than 0.001) and complete recovery at 24 h. In the subsequent experiments rats were divided into four groups. All animals received either saline or BSO 4.5 mmol/kg/day (1000 mg/kg/day) from day 27 to 30 of life and either saline or PMSG 5 IU IP on day 29 of life. BSO reduced ovarian content of GSH (saline-saline compared with BSO-saline, P less than 0.0001), which was countered by the prior administration of PMSG (BSO-saline compared with BSO-PMSG, P less than 0.005). Glutathione levels were as follows: saline-saline 4.3 +/- 0.04; saline-PMSG 5.0 +/- 0.4; BSO-saline 2.13 +/- 0.2; BSO-PMSG 3.24 +/- 0.2 nmol/mg ovary. These findings suggest the ovary is susceptible to GSH depletion by in vivo administration of BSO. Gonadotropin (PMSG) is capable of effecting a partial return of total ovarian GSH content.
Department of Obstetrics and Gynaecology, Foothills Hospital, University of Calgary, Alberta, Canada.
J F
JF
Jarrell
M
M
Sevcik
G
G
Stuart
D000818:Animals; D019328:Buthionine Sulfoximine; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000378:metabolism*; D006064:Gonadotropins, Equine / Q000494:pharmacology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives; D010053:Ovary / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D006064:Gonadotropins, Equine; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione