Ellagic acid alleviates pulmonary inflammation and oxidative stress in mouse model of diisononyl phthalate-induced asthma

Abstract

Polyvinyl chloride is plasticized using diisononyl phthalate (DiNP), and exposure to phthalates has been linked to the emergence of asthma and allergies. The adjuvant impact of DiNP exposure results in allergic airway inflammation. In the current study, we looked into how ellagic acid (ELA) impacted asthma brought on by DiNP. Male BALB/c mice (n=40, 20-30 g) were divided into 4 groups of 10 mice each, and the following treatments were given to each group: group 1 (control) received saline orally for 30 days; group 2 (ELA) received 10 mg/kg of ELA (oral) for 30 days; group 3 (DiNP & ELA) received 10 mg/kg of ELA (oral) for 7 days prior to DiNP (50mg/kg) exposure (intraperitoneal and intranasal); group 4 (DiNP) received 50 mg/kg DiNP. After the last administration, mice were sacrificed, lungs were removed and their bronchoalveolar lavage fluid was collected which was used for biochemical and histopathological analysis. The mice given DiNP had changes in their histoarchitecture, inflammatory cells, antioxidant status, and inflammation markers. Malondialdehyde (MDA) and inflammatory biomarkers (NO, MPO) were considerably higher (p< 0.05) in the lungs of DiNP-treated mice than in the control group. In the lungs, DiNP reduced the concentration of non-enzymatic antioxidants (GSH and AA), and the activity of enzymatic antioxidants (SOD, CAT, and GST). DiNP also altered inflammatory cells (eosinophils, neutrophils, lymphocytes, monocytes, leucocytes) in the BALF. ELA administration ameliorated these changes. Histopathological analysis revealed airway inflammation characterized by inflammatory cell infiltration, oedema, hemorrhage, and constricted alveoli space. Additionally, the mice co-treated with ELA and DiNP experienced mild inflammation of the alveoli and interstitial spaces as well as mild thickening of the alveolar septae. ELA offered a protective effect against DiNP-induced allergic asthma in mice.

Alteration of pulmonary mitochondrial oxidation status, inflammation, energy metabolizing enzymes, oncogenic and apoptotic markers in mice model of diisononyl phthalate-induced asthma

“…This is evident in the findings of this research as DiNP upregulated NO levels and MPO activity, both which are markers of inflammation. The results of this study concur with those of Olajide et al (2023). MPO, a protein found in high concentrations in neutrophils, monocytes, and certain subpopulations of tissue macrophages, is thought to be crucial for both host defences and inflammatory tissue injury.…”

“…Mucus is overexpressed, irritated, and tightened due to enlarged walls and inflammation in contrast to the airways of healthy people which possess a normal airway wall, and relaxed smooth muscle (Shastri et al, 2021). DiNP caused airway inflammation histologically by infiltrating inflammatory cells, oedema, haemorrhage, and limited alveoli space in this study and this is consistent with those of Olajide et al (2023).…”

“…On days 19, 21, and 23, the mice were given an intranasal injection of 50 mg/kg of DiNP diluted in 50 mL of saline. The intranasal injection of 50mg/kg of DiNP was 50µL (Olajide et al, 2023).…”

Assessment of neuro-pulmonary crosstalk in asthmatic mice: effects of DiNP exposure on cellular respiration, mitochondrial oxidative status and apoptotic signaling

“…DiNP exposure has been associated with different forms of physiological impairment such as oxidative stress, leading to the depletion of antioxidants such as reduced glutathione and ascorbic acid, while increasing levels of malondialdehyde (a marker of oxidative damage) 1 , 2 . In the brain, oxidative stress disrupts cellular homeostasis, damages biomolecules, and contributes to neurodegenerative conditions.…”