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Regular Manuscript

Establishing the use of melatonin as an adjuvant therapeutic against paraquat-induced lung toxicity in rats

¹ Gulhane Military Medical Academy
² University of Texas Health Science Center
³ Univ of Texas HSC

^* To whom correspondence should be addressed. E-mail: fizyoter{at}gmail.com.

	Abstract

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 combination a potent anti-inflammatory and antioxidant agent may counteract more of PQ's effects than an anti-inflammatory 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 a toxic dose of 19 mg/kg PQ dissolved in 1 ml saline intraperitoneally. Control animals were injected the same amount of saline only. 1 mg/kg Dex was administered two hours after PQ administration. In the combination treatment group 20 mg/kg Mel was given with Dex. All drugs were given every 12 hours for a total of 6 doses. Five animals in PQ group and three animals in Dex only group died by the end of the study. No death occurred in the Dex+Mel group. Dex exerted improvements in several oxidative and antioxidative parameters. However, combination treatment provides 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