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Propylthiouracil (PTU)-Induced Hypothyroidism Protects Ionizing Radiation-Induced Multiple Organ Damage in Rats

 

Abstract


The objective of this study was to examine the potential radioprotective properties of propylthiouracil (PTU)-induced hypothyroidism against oxidative organ damage induced by irradiation (IR). Sprague Dawley rats were pretreated with saline or PTU (10 mg/kg i.p.) for 15 days, and were then exposed to whole-body IR (800 cGy).

 

 

A group of rats were decapitated at 6-h after exposure to irradiation, while another group was followed for 72-h after IR, during which saline or PTU injections were repeated once daily. Lung, liver, kidney and ileum samples were obtained for the determination of malondialdehyde (MDA; an index of lipid peroxidation) and glutathione (GSH, an antioxidant) levels, myeloperoxidase activity (MPO; an index of tissue neutrophil accumulation) and collagen contents, while oxidant- induced DNA fragmentation was evaluated in the ileal tissues.

 

All tissues were also examined microscopically and assayed for the production of reactive oxidants using chemiluminescence (CL). Lactate dehydrogenase (LDH)-an indicator of tissue damage and TNF- a were assayed in serum samples. Irradiation caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity, CL levels and collagen content of the studied tissues (P<0.05-0.001). Similarly, serum TNF-a and LDH were elevated in the irradiated rats as compared with control group.

 

On the other hand, PTU treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Our results suggest that PTU- induced hypothyroidism reduces oxidative damage in the lung, hepatic, renal and ileal tissues probably due to hypometabolism, which is associated with decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms.

Journal of Endocrinology

Göksel Sener1, Levent Kabasakal1, Beste Melek Atasoy2, Can Erzik3, Ayliz Velioglu-Ögünç4, Sule Çetinel5, Gazi Contuk5, Nursal Gedik6 and Berrak Ç Yegen7 1School of Pharmacy, Department of Pharmacology, School of Medicine, Departments of 2Radiation Oncology, 3Medical Biology, 5Histology-Embriology and 7Physiology, 4Vocational School of Health Related Professions, Marmara University, Haydarpasa, Istanbul 34668 / Turkey 6Division of Biochemistry, Kasimpasa Military Hospital, Istanbul, Turkey