The objective of this study was to examine the potential radioprotective properties of propylthiouracil (PTU)-induced hypothyroidism against oxidative organ damage induced by irradiation. Sprague–Dawley rats were pre-treated with saline or PTU (10 mg/kg i.p.) for 15 days, and were then exposed to whole-body irradiation (800 cGy). A group of rats were decapitated at 6 h after exposure to irradiation, while another group was followed for 72 h after irradiation, 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 tumour necrosis factor-α (TNFα) were assayed in serum samples. Irradiation caused a significant decrease in GSH level, which was accompanied by significant increases in MDA levels, MPO activity, CL levels and collagen content of the tissues studied (P<0.05–0.001). Similarly, serum TNFα and LDH were elevated in the irradiated rats as compared with the control group. On the other hand, PTU treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Our results suggested 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.

Alendronate sodium, a primary amino bisphosphonate, is widely used in the treatment of various diseases that are associated with bone resorption, such as postmenopausal osteoporosis and Paget’s disease of bone. Although the adverse effects of biphosphonates on the gastrointestinal system have been demonstrated in experimental and clinical studies, the exact mechanisms underlying this damage are not clear yet. Ghrelin, a 28 amino acid peptide produced predominantly by the stomach, was shown to exert a potent protective action on the stomach of rats exposed to ethanol or stress.

Our objective was to evaluate the possible anti-oxidant and anti-inflammatory effects of ghrelin against alendronate-induced gastric damage. Wistar albino rats were administered alendronate (20 mg/kg) by gavage for 4 days, along with either ghrelin (10 ng/kg per day) or saline given i.p. After decapitation, stomach tissues were removed for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and tissue collagen content, while the extent of tissue damage was analyzed microscopically. Formation of reactive oxygen species was determined by chemiluminesence using a luminol probe in fresh gastric tissues. Serum tumor necrosis factor (TNF-α) and lactate dehydrogenase levels were assessed in trunk blood.

Oral administration of alendronate-induced significant gastric damage, accompanied by increased MPO activity, collagen content, MDA and luminol levels (P< 0.01–P< 0.001), while tissue GSH was decreased (P< 0.01). On the other hand, ghrelin treatment reversed these alterations (P< 0.05–P<0.001) as well as elevating serum TNF-α levels significantly (P< 0.001).

The findings of the present study suggest that alendronate induces oxidative gastric damage by a local irritant effect, and ghrelin ameliorates this damage by its possible antioxidant and anti-inflammatory properties.