Melatonin protects against ionizing radiation‐induced oxidative damage in corpus cavernosum and urinary bladder in rats

Abstract:  The objective of this study was to examine the potential radioprotective properties of pharmacological doses of melatonin on corpus cavernosum and bladder tissues of whole‐body irradiated (IR) rats. A total of 32 male Sprague–Dawley rats were exposed to irradiation performed with a LINAC which produced 6 MV photons at a focus 100 cm distant from the skin. Under ketamine anesthesia, each rat received a single whole‐body dose of 800 cGy. Immediately before and after IR, rats were treated with either saline or melatonin (20 and 10 mg/kg, i.p.) and decapitated at 12 hr after exposure to irradiation. Another group of rats was followed for 72 hr after IR, where melatonin injections were repeated once daily. Tissue levels of malondialdehyde (MDA), an index of lipid peroxidation, and glutathione (GSH), a key antioxidant, were estimated in corpus cavernosum and urinary bladder. Tissues were also examined microscopically. The results demonstrate that both 12 and 72 hr following IR, tissue levels of MDA were elevated (P < 0.001), while GSH levels were reduced (P < 0.01) in both tissues. On the other hand, melatonin reversed these changes significantly (P < 0.05–0.01), concomitant with the improvement in histological appearances. Our results show that whole‐body irradiation causes oxidative damage in the tissues of the genitourinary system. As melatonin administration reversed oxidative organ injury, as assessed by biochemical and histopathological findings, it is suggested that supplementing cancer patients with adjuvant therapy of melatonin may have some benefit for successful radiotherapy.

[1]  Sato Honma,et al.  Melatonin induces γ-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells , 1999 .

[2]  Vijayalaxmi,et al.  Melatonin: from basic research to cancer treatment clinics. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  B. Yeğen,et al.  Melatonin ameliorates ionizing radiation-induced oxidative organ damage in rats. , 2003, Life sciences.

[4]  S. Szabó,et al.  Glutathione, protein sulfhydryls and cysteine proteases in gastric mucosal injury and protection. , 1992, Clinica chimica acta; international journal of clinical chemistry.

[5]  J. Ward,et al.  DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability. , 1988, Progress in nucleic acid research and molecular biology.

[6]  D. Chandra,et al.  Radiation induced oxidative stress: II Studies in liver as a distant organ of tumor bearing mice , 2001, Molecular and Cellular Biochemistry.

[7]  R. Reiter,et al.  Actions of Melatonin in the Reduction of Oxidative Stress , 2000, Journal of Biomedical Science.

[8]  G. Şener,et al.  The effects of melatonin on ischemia-reperfusion induced changes in rat corpus cavernosum. , 2002, The Journal of urology.

[9]  Vanesa Martín,et al.  Regulation of antioxidant enzymes: a significant role for melatonin , 2004, Journal of pineal research.

[10]  E. Beutler Glutathione in red blood cell metabolism , 1975 .

[11]  G. Şener,et al.  Melatonin treatment protects against ischemia/reperfusion‐induced functional and biochemical changes in rat urinary bladder , 2003, Journal of pineal research.

[12]  M. Sevilla,et al.  Influence of oxygen on the repair of direct radiation damage to DNA by thiols in model systems. , 1994, International journal of radiation biology.

[13]  A. M. Lefer,et al.  Cardiac venous endothelial dysfunction after myocardial ischemia and reperfusion in dogs. , 1992, The American journal of physiology.

[14]  Z. Mornjaković,et al.  [Morphometric characteristics of thyroid cells in irradiation-stressed rats treated with pinealectomy and melatonin]. , 1992, Medicinski arhiv.

[15]  Seyithan Taysi,et al.  Melatonin reduces lipid peroxidation and nitric oxide during irradiation‐induced oxidative injury in the rat liver , 2003, Journal of pineal research.

[16]  S. Aust,et al.  Microsomal lipid peroxidation. , 1978, Methods in enzymology.

[17]  R. Reiter,et al.  Melatonin: reducing the toxicity and increasing the efficacy of drugs , 2002, The Journal of pharmacy and pharmacology.

[18]  M. Kassayová,et al.  The influence of melatonin on metabolic changes in female rats induced by continuous irradiation and/or administration of 7,12-dimethylbenz/a/anthracene. , 1997, Neoplasma.

[19]  R. Reiter,et al.  A review of the evidence supporting melatonin's role as an antioxidant , 1995, Journal of pineal research.

[20]  Z. Mornjaković,et al.  [Morphometric characteristics of Leydig cells after total irradiation of rats treated with melatonin]. , 1998, Medicinski arhiv.

[21]  R. Krane,et al.  Overactivity and structural changes in the chronically ischemic bladder. , 1999, The Journal of urology.

[22]  C. Gentile,et al.  The chemistry of melatonin's interaction with reactive species , 2003, Journal of pineal research.

[23]  Z. Kundurović,et al.  Histoenzymological reactions of the thyroid gland in irradiated and previously melatonin-treated irradiated rats. , 1989, Acta medica Iugoslavica.

[24]  R. Reiter,et al.  Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. , 2000, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[25]  Z. Mornjaković,et al.  [Morphometric aspects of seminiferous tubules in rats treated with melatonin and whole body irradiation (stereologic analysis)]. , 1991, Medicinski arhiv.

[26]  Vijayalaxmi,et al.  Melatonin reduces gamma radiation-induced primary DNA damage in human blood lymphocytes. , 1998, Mutation research.