RESUMEN
OBJECTIVES: In addition to its antimicrobial effects, inhibitory effects of minocycline have been demonstrated, including against inflammation, apoptosis, proteolysis, angiogenesis, and tumor metastasis. In this study, we aimed to determine the beneficial effects of minocycline on lung histology and its antioxidant activity in a murine model of pulmonary fibrosis. MATERIALS AND METHODS: Twenty-eight Swiss albino mice were randomly allocated into four groups of seven animals per group. Group I (control group) received intraperitoneal injection of saline. Group II (methotrexate group) received methotrexate orally 3 mg/kg for 28 days. Group III (minocycline group) received methotrexate orally 3 mg/kg and 15 mg/kg of intraperitoneally injected minocycline for 28 days. Group IV (minocycline group) received 15 mg/kg of intraperitoneally injected minocycline for 28 days. Twenty-eight days later, the animals were euthanized. Thereafter, lung tissue samples were harvested. Histological findings of airways were evaluated by light microscopy. The levels of malondialdehyde (MDA), the product of reactive oxygen in lung tissue, and catalase, an antioxidant enzyme, were also determined. RESULTS: In the light microscopic examination, the lung tissues of the control group showed normal histological features. In the methotrexate group, the degree of lung damage (grade 3 fibrosis) was higher than the control and other groups (p: 0.001). In the minocycline-treated group, improvement in lung tissue was noted (median fibrosis score: 3 (MTX group) vs 1 (MTX plus minocycline group); p: 0.001). Only the minocycline group showed normal histological features. Although minocycline reduced the MDA levels in lung tissue, an increase in catalase activity was detected (p: 0.018 and p: 0.014, respectively). CONCLUSIONS: The administration of minocycline may be effective in MTX-induced lung fibrosis in mice. However, further studies with high-dose and long-term treatments are needed.
Asunto(s)
Antioxidantes/farmacología , Pulmón/efectos de los fármacos , Metotrexato , Minociclina/farmacología , Fibrosis Pulmonar/prevención & control , Animales , Catalasa/metabolismo , Citoprotección , Modelos Animales de Enfermedad , Pulmón/metabolismo , Pulmón/patología , Malondialdehído/metabolismo , Ratones , Estrés Oxidativo/efectos de los fármacos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Factores de TiempoRESUMEN
AIM: The study is aimed to determine the beneficial effects of methyl palmitate (MP) which has antioxidant and anti-inflammatory effects demonstrated on murine model of acute lung injury induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: Forty male BALB/C mice were randomly allocated into four groups (n=10, each): control group, methyl palmitate group (300 mg/kg), LPS group, and methyl palmitate -treated groups. Methyl palmitate or vehicle was given with an intraperitoneal administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge. All experimental procedures complied with the requirements of the Animal Care and Ethics Committee of the Adnan Menderes University. RESULTS: Methyl palmitate pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. Methyl palmitate pretreatment also reduced the concentrations of malondialdehyde in lung tissues. CONCLUSIONS: This study indicates that methyl palmitate may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may involve the inhibition of NF-κB. activation.