Surgical stress increases renal glutathione content via increased glucocorticoid, and resistance to subsequent oxidative injury in the rat: Significant link between endocrine response and cell defense system under the stress

Systemic and nonspecific stress response effects on the cellular defense me chanism were studied in the male rat kidney. Two days after laparotomy-indu ced surgical stress, rats showed increased serum corticosterone and renal c ortical reduced glutathione (GSH). Rats were then injected s.c. with mercur ic chloride (HgCl2) to oxidatively injure renal tubuli. Increased serum cre atinine levels indicated that laparotomy pretreatment lessened renal damage . To study the effects of the activated pituitary-adrenal axis on renal cor tical GSH content and vulnerability to subsequent oxidative injury, rats we re injected s.c. with ACTH on two consecutive days. ACTH administration inc reased both corticosterone and aldosterone. These rats showed increased, do se-dependent renal cortical GSH content, i.e., controls (n=7): 1.25 +/- 0.2 3 mu mol/g tissue, daily dose of 10 mu g/100 gBW (n=7): 1.53 +/- 0.24 mu mo l/g tissue, and daily dose of 40 mu g/100 gBW (n=7): 2.31 +/- 0.23 mu mol/g tissue. Rats receiving daily doses of 40 mu g of ACTH/100 gBW acquired res istance to oxidative injury, indicated by serum creatinine levels: controls (n=6), 22 +/- 4 mu mol/L; HgCl2 (n=6), 145 +/- 88 mu mol/L; ACTH and HgCl2 (n=6), 37 +/- 11 mu mol/L. Morphological evidence indicated that ACTH pret reatment in HgCl2-injected rats prevented renal tissue from inflammatory ce ll infiltration but not from tubular degeneration. Cellular GSH content of LLC-PK1 cells, porcine renal-tubule-derived culture cells, increased signif icantly in incubation with dexamethasone or aldosterone, suggesting that ad renal steroids directly stimulate renal cell GSH. We demonstrated that stre ss or ACTH administration activates the defense mechanism in the kidney via increased GSH. This stress-activatable defense system may therefore indica te a connection between endocrine stress response and the cellular defense mechanism.