Abstract
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.
Highlights
Paraquat (PQ, 1,1-dimethyl-4,4-bipyridinium dichloride) is one of the most widely used herbicides globally, mainly in developing countries [1]
The bronchi exhibited a normal cuboidal epithelium that ended with a terminal bronchus that communicated directly with the respiratory portion
The respiratory portion consisted of many alveoli that were lined with two types of alveolar epithelial cells, type I pneumocytes, and type II pneumocytes
Summary
Paraquat (PQ, 1,1-dimethyl-4,4-bipyridinium dichloride) is one of the most widely used herbicides globally, mainly in developing countries [1]. PQ induces pulmonary fibrosis, and oxidative stress plays an important role in this process since the oxidation–reduction. Molecules 2019, 24, 1498 reactions of PQ produce reactive oxygen species (ROS). These species damage alveolar epithelial cells and are assumed to be responsible for direct cell injury [6,7,8]. PQ causes lung toxicity and fibrosis through several molecular mechanisms, such as caspase cleavage, matrix metalloproteinase-9 (MMP-9), peroxisome proliferator-activated receptor-gamma (PPAR-γ), nuclear factor-kappaB (NF-κB), Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK), Nuclear factor-like2/NADPH oxidase (Nrf2/Nox4) redox balance, and transforming growth factor-beta/small mothers against decapentaplegic (TGF-β1/Smad3) signaling pathways [9,10,11,12,13,14]
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