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ORIGINAL RESEARCH ARTICLE

Establishing the Use of Melatonin as an Adjuvant Therapeutic Against Paraquat-Induced Lung Toxicity in Rats

Ercan Göcgeldi^*, Bülent Uysal, Ahmet Korkmaz^,, Recai Ogur, Russel J. Reiter, Bülent Kurt^||, Sükrü Öter^,1, Turgut Topal and Metin Hasde^*

^* Department of Public Health and Department of Physiology, Gülhane Military Medical Academy, Ankara, Turkey 06018; Department of Cellular and Structural Biology, University of Texas, Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Environmental Medicine and ^|| Department of Pathology, Gülhane Military Medical Academy, Ankara, Turkey 06018

To whom requests for reprints should be addressed at ¹ Gülhane Askeri Tip Akademisi, Fizyoloji Anabilim Dali, 06018 – Etlik / Ankara, Turkey. E-mail: fizyoter{at}gmail.com; oters{at}gata.edu.tr

It is well known that the intake of paraquat (PQ) causes severe tissue injury leading to numerous fatalities. Considering that the main target for PQ toxicity is the lung and involves the production of reactive oxygen and nitrogen species, transcription factors and inflammatory cytokines, it may be hypothesized that the combination of a potent antiinflammatory and antioxidant agent may counteract more of PQ’s effects than an antiinflammatory agent alone. For this purpose, combination of dexamethasone (Dex) and melatonin (Mel) was compared with Dex alone. A total of 40 male Wistar albino rats were divided into four groups as control, PQ, Dex only, and Dex plus Mel. The animals were given intraperitoneally a toxic dose of 19 mg/kg PQ dissolved in 1 ml saline. Control animals were injected with the same amount of saline only. A dose of 1 mg/kg Dex was administered 2 hrs after PQ administration. In the combination treatment group, 20 mg/kg Mel was given with Dex. All drugs were given every 12 hrs for a total of six doses. Five animals in PQ group and three animals in Dex only group died by the end of the study. No deaths occurred in the Dex+Mel group. Dex exerted improvements in several oxidative and antioxidative parameters. However, combination treatment provided beneficial effects against PQ toxicity far greater than Dex alone. This difference was also apparent when tissues were histologically compared. In conclusion, Mel exhibited strong additive beneficial effects with Dex and can be considered as a safe treatment modality against PQ toxicity.

Key Words: paraquat • lung damage • nitrosative stress • oxidative stress • dexamethasone • melatonin