Aminoguanidine ameliorates radiation-induced oxidative lung damage in rats

Abstract

Clin Invest Med 2008; 31 (4): E182-E188.Abstract Purpose: To investigate the possible protective effects of aminoguanidine (AG ) on lung damage in whole body irradiated rats. Methods: To evaluate the biological damage of radiation on rat lung tissue, lipid peroxidation products were measured using biochemical parameters. Thirty Wistar albino rats were divided into three subgroups: control (C) , irradiation alone (RT), and RT + AG combined. After sacrificing the rats, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities and malondiadehyde (MDA), nitric oxide (NO) levels were evaluated in lung tissue. Results: Administration of AG resulted in an increase in the activities of CAT, SOD and GSHPx in the lungs. All were reduced after radiatio. In addition, AG administration resulted in a decrease in both NO and MDA levels in lung compared with the irradiated group. Conclusion: Amnoguanidine increased the endogenous antioxidant defence mechanism in rats and protected the animals from radiation-induced lung toxicity. Moreover, AG may protect against ionizing radiation-induced lung damage because of its antioxidant effect.Radiation therapy (RT) is a crucial component of application for many thoracic malignancies. Radiationinduced lung toxicity remains a major factor that limits the ability to escalate radiation doses in the application of thoracic tumours. RT-related pulmonary symptoms occur in up to 30% of patients irradiated for lung cancer, breast cancer, lymphoma, or thymoma. Pulmonary toxicity from thoracic irradiation is also an important problem in other settings, including combined modality treatment of Hodgkin's disease and esophageal cancer, and bone marrow transplantation with total body irradiation. 1 Ionizing radiation is a well-established carcinogen due to the resulting oxidative damage, and the molecule most often reported to be damaged by this physical agent is DNA. 2 Aproximately 60-70% of cellular DNA damage produced by ionizing radiation is caused by OH, formed from the radiolysis of water. 3 Besides DNA, lipids and proteins are also attacked by free radicals induced by ionizing radiation. 4 Lipid peroxidation is believed to be an important cause of destruction and damage to cell membranes and has been suggested to be a contributing factor to the development of oxygen radicals-mediated tissue damage. 5 Oxidative stress occurs when there is excessive free radical production and/or low antioxidant defence, and results in chemical alterations of biomolecules causing structural and functional ORIGINAL RESEARCH

Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide‐induced hemorrhagic cystitis in rat

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Protective effect of aminoguanidine against cyclophosphamide-induced oxidative stress and renal damage in rats

“…[11][12][13][14][15][16] In a recent study, 17 AG has been shown to reduce cisplatin-induced nephrotoxicity due to its antioxidant effect. In another recent study, 18 AG has been shown to increase the endogenous antioxidant defense mechanism in rats and protect the animals from radiation-induced lung toxicity. AbdelZaher et al 19 have shown that AG markedly inhibits acetaminophen-induced hepatic and renal depletion of antioxidants as well as nitric oxide overproduction.…”

Role of Migratory Inhibition Factor in Age-Related Susceptibility to Radiation Lung Injury via NF-E2–Related Factor–2 and Antioxidant Regulation

“…Oxidative stress is a major factor in the initiation and perpetuation of RILI (20)(21)(22). Our previous expression-profiling data from radiated mouse lungs demonstrated significant deregulation of the redox-sensitive transcription factor NF-E2-related factor-2 (Nrf2) in RILI (23), a key protein in orchestrating cellular antioxidant defenses and maintaining redox homeostasis.…”