Alteration of Activities of Hepatic Antioxidant Defence Enzymes in Developing Chick Embryos After Glucocorticoid Administration - A Factor to Produce Some Adverse Effects?

Abstract

Liver tissue is one of the principal targets of glucocorticoids, therefore changes in the balance between hepatic oxidative and reductive capacity may greatly influence adverse effects of glucocorticoid therapy. In this study, effects of glucocorticoid on the activities of hepatic antioxidant defence enzymes were examined by using developing chick embryos. After the administration of 0.25 micromol hydrocortisone sodium succinate, a typical glucocorticoid, to 15-day-old chick embryos, glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase in the liver generally began to decrease at around 4 h, reaching 60-70% of control levels between 24 and 48 h. These changes were observed much earlier than the elevation of the hepatic thiobarbituric acid reacting substance (TBARS) level which began to increase from 20h, reaching about six times the control level at 48 h after hydrocortisone administration. Conversely, the elevated TBARS level decreased back to the normal level with the recoveries of these enzyme activities. Furthermore, it was found that the aniline hydroxylase activity, measured as a marker of oxidative activity, began to increase after around 12 h. These results suggested that TBARS levels were possibly produced by the suppression of antioxidant defence abilities and the significant induction of oxidative activity in the liver by glucocorticoid. As the elevated TBARS in the liver can be distributed to tissues, TBARS will be involved in the occurrence of some of the glucocorticoid-induced adverse effects such as cataract formation.

Walker‐256 tumor growth causes oxidative stress in rat brain

“…1996). The increase in plasma levels of glucocorticoids may be partially responsible for the inhibition of this enzyme in the tumor‐bearing rats (Argiles and Azcon‐Bieto 1988; Lee et al . 1998).…”

Suppressive Effects of Thyroxine on Glucocorticoid (GC)-induced Metabolic Changes and Cataract Formation on Developing Chick Embryos

“…Effect of thyroxine (T4) on the elevation in serum triglyceride and non-esteri®ed fatty acid (NEFA) In chick embryos, GC alters the activities of antioxidant defense enzymes in the liver (Lee, Iwatsuru and Nishigori, 1998), which can result in the elevation of LPO in humoral components such as liver. Based on our previous ®ndings, GC-induced cataracts may be induced by oxidative stress that possibly arises in the liver (Nishigori et al, 1984b;Lee et al, 1991;Setogawa et al, 1994;Watanabe et al, 2000).…”

Changes in the glutathione system of lung cell lines after treatment with hydrocortisone

“…Therefore, it was surprising to find a decrease in GSH content of the alveolar epithelial cells in this study. Only the ocular lens is known to show a decrease in GSH levels after GC treatment, which might lead to cataracts as observed in man and animal (Lee et al 1998;Setogawa et al 1994). On the other hand, Rahman et al (1999) also found a decrease of glutamylcysteine synthetase heavy chain (the catalytic subunit of the rate limiting enzyme in glutathione synthesis) in A549 cells, leading to a decreased GSH content, after dexamethasone administration.…”