Effects of different antioxidants on lipid peroxidation in brain homogenates, induced by L-thyroxine administration in rats.

OBJECTIVE: It is known that thyrotoxicosis induces lipid peroxidation (LPO). In contrast, propylthiouracil (PTU), a thyrostatic drug is a well-known antioxidant. Also melatonin has been shown to protect against free radical-induced neuronal destruction. At the same time, it is generally accepted that the brain is the most vulnerable tissue to oxidative stress.

METHODS: The goal of the study was to examine the components of LPO, i.e., conjugated dienes (CD), malondialdehyde (MDA) and Schiff's bases (SB), in the brain of male Wistar rats. Two experiments were performed, with two control groups created for each experiment: Group 1--intact animals and Group 2--animals injected with 0.9% NaCl. In Experiment I, the animals received L-thyroxine (L-T4) in a dose of 100 microg/kg BW, i.p., daily, for two weeks (Groups 3-5). After one week of L-T4 treatment, the following agents were added during a subsequent week: Group 4--PTU in drinking water (45 mg/kg BW/day); Group 5--melatonin (5 mg/kg BW, daily). In Experiment II, lasting 7 days, the animals were divided into the following groups: Group 1--intact animals; Group 2--animals injected with 0.9% NaCl; Group 3--PTU in drinking water (45 mg/kg BW/day); Group 4--melatonin (5 mg/kg BW, daily).

RESULTS: In Experiment I, we observed a significantly higher SB level in saline treated animals and a significant increase in both CD and SB levels in rats treated with L-T4, compared to those in non treated control. CD levels were also elevated in rats treated with L-T4, compared to values in the saline only treated animals. Melatonin and PTU reduced CD levels and melatonin diminished SB levels, as compared to those in L-T4-treated rats. In Experiment II, we observed significantly higher CD, SB and MDA levels in saline treated rats, when compared to respective values in non treated control. Melatonin decreased CD levels, when compared to CD levels in both the non treated and saline injected controls. Additionally, melatonin reduced SB levels relative to change in the brains of saline treated rats. Furthermore, PTU decreased CD levels in brain homogenates compared to non-treated animals.

CONCLUSIONS: (1) L-thyroxine administration stimulates LPO in the rat brain; (2) All the examined antioxidants decrease LPO in L-T4-administered animals; (3) All the examined antioxidants reduce the basal LPO; 4) Stress, when induced by handling, intensifies oxidative processes in the organism.