Reactive oxygen species involvement in ricin-induced thyroid toxicity in rat.

Ricin is known to have diverse effects on the cells of different organs like liver, kidney, pancreas, intestines and parathyroid. Acute decrease in serum thyroid hormone level 24 h after ricin administration (1.5 micrograms/100 g) led us to suspect the toxic action of ricin on the thyroid. We monitored the lipid peroxidation (LP) and anti-oxidant status of the thyroid tissue to determine the role, if any, played by reactive oxygen species (ROS) in this pathology. An increase of 39% in LP and 47% in superoxide dismutase, along with a 8.5% decrease in catalase points to the imbalance in the antioxidant defence involving hydrogen peroxide and its univalent reduction product, the hydroxyl radical. Thyroid histopathology shows destruction of thyroid follicles and necrosis, which may be due to ROS and may partly explain the 50% reduction in circulating thyroid hormones seen after ricin administration.

Changes in lipid peroxide levels and the activity of reactive oxygen scavenging systems in thyroid tissue after exposure to radioactive iodine in rats.

Exposure to ionizing radiation causes radiolysis of water in tissues leading to generation of reactive oxygen species (ROS), which are known to affect the antioxidant defense systems and induce lipid peroxidation (LP). Use of radioactive iodine (131I) for diagnosis and therapy of thyroid disorders may also generate ROS in the thyroid. Early (24 and 48 hours) and late (18 days) effects of subablation doses of 131I (370/555/1110 kBq) on the antioxidant defense and LP in the thyroid tissues have been studied. LP was elevated in all 131I treated groups by 10% to 41%. Although there was no change in catalase (CAT), the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities showed evidence of change from 48 hours onwards--SOD decreased by 32% to 56% and GPx increased by 15% to 43%. Nonprotein thiols (reduced glutathione, GSH) showed an elevation of 16% at 24 hours, but later declined by 15% by day 18 after 370 KBq of 131I. Thus, the increase in LP observed may be due to beta irradiation induced ROS by 131I. The parallel decrease in SOD could be due to inactivation by ROS. The increase in GPx may be a consequence of induction due to elevated LP and/or ROS, which may be inadequate to lower the LP. In spite of elevated LP, the thyroid function appears to be normal.

Role of tissue antioxidant defence in thyroid cancers.

Reactive oxygen species (ROS), consisting mainly of superoxide, hydrogen peroxide and hydroxyl radical, have been implicated in many diseases including cancer. ROS have been known to play an important role in the initiation and promotion of multistage carcinogenesis. The cellular antioxidant defence plays a crucial role in neoplastic disease. However, very little is known about the tissue antioxidant defence in thyroid cancers. We therefore undertook a study to assess the role of ROS in the pathogenesis of thyroid cancers. Our samples consisted of post-operated thyroid tissues (normal, goiters, follicular adenomas, follicular carcinomas and papillary carcinomas). The parameters studied were lipid peroxidation (LP), antioxidant enzymes--superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)--and non-protein thiols (GSH). Compared to normal thyroid no changes were seen in goiters. LP was significantly higher in adenomas (16%) and carcinomas (60-69%). SOD was decreased by 15% in adenomas while in carcinomas it increased by 9-12%. GPx was raised in carcinomas by 10-21%. Follicular carcinomas showed a 4% increase in CAT activity while GSH was raised in adenomas and papillary carcinomas by 17%. Thus, in adenomas (initial stage) involvement of superoxide radicals and in carcinomas (later stage) hydrogen peroxide and, possibly, hydroxyl radical involvement cannot be ruled out. These ROS may be responsible for elevated LP observed in adenomas and carcinomas.