Responses of brain cytosolic and microsomal glutathione S-transferases to theophylline in adult and suckling rats
Responses of brain cytosolic and microsomal glutathione (GSH) S-transferases (GSTs) to the effects of various doses of theophylline have been investigated in adult and suckling rats. Normally cytosolic GSH content and activities of GSTs were higher in adult brain as compared to those in growing rats. Different doses of theophylline (10, 20, 30 and 50 mg/kg b.w) have been examined and comparative studies have been carried out with a dose of 50 mg/kg. A single i.p dose of the drug resulted in a maximum 25 and 55% depletion in cytosolic brain GSH in adult and suckling rats, respectively. Depletion of GSH in brain of adult and growing rats was noticed 4 hrs after theophylline injection, but the time of resynthesis was relatively slow in the developing brain. It is interesting to note that the level of GSH remains significantly high for at least 24 hrs after theophylline injection in the growing brain. Additionally, brain microsomal and cytosolic GSTs have been induced (p<0.05) due to theophylline, in suckling rats as compared to those of adults. The maximum rate of induction of both cytosolic and microsomal GSTs in growing brain was 1.8 and 2.7-times, respectively.. These results together with SDS-PAGE data obtained from the analysis of affinity-purified GSTs, showed that the pattern of changes in GST classes in both age groups is different. In addition to microsomal GST, a-class of cytosolic enzyme (GST-alpha) is differentially induced in the brains of the two age groups in response to theophylline. It is suggested that the response of glutathione system is implicated in the protection against theophylline-mediated oxidative stress due to the bulk of the drug, which is believed to cross-underdeveloped blood-brain barrier in immature rats.