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Open AccessArticle

Melittin Exerts Beneficial Effects on Paraquat-Induced Lung Injuries in Mice by Modifying Oxidative Stress and Apoptosis

Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt
Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan
Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-75123 Uppsala, Sweden
International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
Author to whom correspondence should be addressed.
Academic Editor: Paula A.C. Gomes
Molecules 2019, 24(8), 1498;
Received: 4 March 2019 / Revised: 5 April 2019 / Accepted: 8 April 2019 / Published: 16 April 2019
(This article belongs to the Special Issue Bioactive Peptides—From Therapy to Nutrition)
Melittin (MEL) is a 26-amino acid peptide with numerous biological activities. Paraquat (PQ) is one of the most widely used herbicides, although it is extremely toxic to humans. To date, PQ poisoning has no effective treatment, and therefore the current study aimed to assess for the first time the possible effects of MEL on PQ-induced lung injuries in mice. Mice received a single intraperitoneal (IP) injection of PQ (30 mg/kg), followed by IP treatment with MEL (0.1 and 0.5 mg/kg) twice per week for four consecutive weeks. Histological alterations, oxidative stress, and apoptosis in the lungs were studied. Hematoxylin and eosin (H&E) staining indicated that MEL markedly reduced lung injuries induced by PQ. Furthermore, treatment with MEL increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity, and decreased malonaldehyde (MDA) and nitric oxide (NO) levels in lung tissue homogenates. Moreover, immunohistochemical staining showed that B-cell lymphoma-2 (Bcl-2) and survivin expressions were upregulated after MEL treatment, while Ki-67 expression was downregulated. The high dose of MEL was more effective than the low dose in all experiments. In summary, MEL efficiently reduced PQ-induced lung injuries in mice. Specific pharmacological examinations are required to determine the effectiveness of MEL in cases of human PQ poisoning. View Full-Text
Keywords: paraquat; lung injury; melittin; oxidative stress; apoptosis paraquat; lung injury; melittin; oxidative stress; apoptosis
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MDPI and ACS Style

El-Aarag, B.; Magdy, M.; AlAjmi, M.F.; Khalifa, S.A.; El-Seedi, H.R. Melittin Exerts Beneficial Effects on Paraquat-Induced Lung Injuries in Mice by Modifying Oxidative Stress and Apoptosis. Molecules 2019, 24, 1498.

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