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 mechanism were studied in the male rat kidney. Two days after laparotomy-induced surgical stress, rats showed increased serum corticosterone and renal cortical reduced glutathione (GSH). Rats were then injected s.c. with mercuric chloride (HgCl2) to oxidatively injure renal tubuli. Increased serum creatinine levels indicated that laparotomy pretreatment lessened renal damage. To study the effects of the activated pituitary-adrenal axis on renal cortical GSH content and vulnerability to subsequent oxidative injury, rats were injected s.c. with ACTH on two consecutive days. ACTH administration increased both corticosterone and aldosterone. These rats showed increased, dose-dependent renal cortical GSH content, i.e., controls (n=7): 1.25 +/- 0.23 micromol/g tissue, daily dose of 10 microg/100 gBW (n=7): 1.53 +/- 0.24 micromol/g tissue, and daily dose of 40 microg/100 gBW (n=7): 2.31 +/- 0.23 micromol/g tissue. Rats receiving daily doses of 40 microg of ACTH/100 gBW acquired resistance to oxidative injury, indicated by serum creatinine levels: controls (n=6), 22 +/- 4 micromol/L; HgCl2 (n=6), 145 +/- 88 micromol/L; ACTH and HgCl2 (n=6), 37 +/- 11 micromol/L. Morphological evidence indicated that ACTH pretreatment in HgCl2-injected rats prevented renal tissue from inflammatory cell infiltration but not from tubular degeneration. Cellular GSH content of LLC-PK1 cells, porcine renal-tubule-derived culture cells, increased significantly in incubation with dexamethasone or aldosterone, suggesting that adrenal steroids directly stimulate renal cell GSH. We demonstrated that stress or ACTH administration activates the defense mechanism in the kidney via increased GSH. This stress-activatable defense system may therefore indicate a connection between endocrine stress response and the cellular defense mechanism.
Ogasawara
M
M
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Japan.
Nomura
K
K
Shibata
N
N
Ujihara
M
M
Kobayashi
M
M
Demura
H
H
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants; D002460:Cell Line; D003345:Corticosterone / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007813:Laparotomy; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000209:etiology / Q000378:metabolism*; D013552:Swine
D000975:Antioxidants; D005938:Glucocorticoids; D000450:Aldosterone; D008627:Mercuric Chloride; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003404:Creatinine; D003345:Corticosterone