Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model
Diisononyl phthalate (DiNP) has been associated with the development of allergies, asthma, and allergic airway inflammation. Through a complex interplay of signals and feedback mechanisms, the lungs communicate with the heart to ensure maintenance of homeostasis and supporting the body’s metabolic d...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2024
|
| Online Access: | http://psasir.upm.edu.my/id/eprint/114669/ http://psasir.upm.edu.my/id/eprint/114669/1/114669.pdf |
| _version_ | 1848866561298792448 |
|---|---|
| author | Kehinde, Samuel Abiodun Olajide, Abosede Temitope Fatokun, Tolulope Peter Faroud, Dalia Hadi, Najah R. Elgazzar, Ahmed M. James, Adewale Segun Ashour, Mohamed H. Mazhar |
| author_facet | Kehinde, Samuel Abiodun Olajide, Abosede Temitope Fatokun, Tolulope Peter Faroud, Dalia Hadi, Najah R. Elgazzar, Ahmed M. James, Adewale Segun Ashour, Mohamed H. Mazhar |
| author_sort | Kehinde, Samuel Abiodun |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Diisononyl phthalate (DiNP) has been associated with the development of allergies, asthma, and allergic airway inflammation. Through a complex interplay of signals and feedback mechanisms, the lungs communicate with the heart to ensure maintenance of homeostasis and supporting the body’s metabolic demands. In the current study, we assessed the crosstalk between DiNP-induced asthma and cardiac cellular respiration, oxidative stress, apoptotic potential, and induction of oncogenic factors. Ten male BALB/c mice with a weight range of 20–30 g were divided into two groups, each comprising five mice. Group 1 (control), was administered saline orally for a duration of 30 days. In contrast, group 2 (DiNP group), received 50 mg/kg of DiNP to induce asthma. After the final administration and asthma induction, the mice were euthanized, and their hearts were excised, processed, and subjected to biochemical analyses. The DiNP group had downregulated (P < 0.05) activities of the enzymes of glycolysis, tricyclic acid cycle, and electron transport chain except the hexokinase and succinate dehydrogenase activity which were upregulate relative to control. Also, oxidative distress markers (GSH, CAT, and MDA and SOD) were also perturbed. Biomarkers of inflammation (MPO and NO) were considerably higher (P < 0.05) in the heart of DiNP-induced asthma mice as compared with the control group. Furthermore, DiNP-induced asthma group has an increased cardiac caspase-3, Bax, c-Myc and K-ras, and p53 while the Bcl2 decreased when compared with control. Overall, the findings indicate that DiNP-induced asthma impairs cardiac functions by induction of key cardiac oncogenes, downregulation of cardiac energy, transduction of enzymes, and promotion of oxidative stress and cellular death. Graphical abstract: (Figure presented.). |
| first_indexed | 2025-11-15T14:22:33Z |
| format | Article |
| id | upm-114669 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:22:33Z |
| publishDate | 2024 |
| publisher | Springer |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1146692025-01-22T08:09:25Z http://psasir.upm.edu.my/id/eprint/114669/ Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model Kehinde, Samuel Abiodun Olajide, Abosede Temitope Fatokun, Tolulope Peter Faroud, Dalia Hadi, Najah R. Elgazzar, Ahmed M. James, Adewale Segun Ashour, Mohamed H. Mazhar Diisononyl phthalate (DiNP) has been associated with the development of allergies, asthma, and allergic airway inflammation. Through a complex interplay of signals and feedback mechanisms, the lungs communicate with the heart to ensure maintenance of homeostasis and supporting the body’s metabolic demands. In the current study, we assessed the crosstalk between DiNP-induced asthma and cardiac cellular respiration, oxidative stress, apoptotic potential, and induction of oncogenic factors. Ten male BALB/c mice with a weight range of 20–30 g were divided into two groups, each comprising five mice. Group 1 (control), was administered saline orally for a duration of 30 days. In contrast, group 2 (DiNP group), received 50 mg/kg of DiNP to induce asthma. After the final administration and asthma induction, the mice were euthanized, and their hearts were excised, processed, and subjected to biochemical analyses. The DiNP group had downregulated (P < 0.05) activities of the enzymes of glycolysis, tricyclic acid cycle, and electron transport chain except the hexokinase and succinate dehydrogenase activity which were upregulate relative to control. Also, oxidative distress markers (GSH, CAT, and MDA and SOD) were also perturbed. Biomarkers of inflammation (MPO and NO) were considerably higher (P < 0.05) in the heart of DiNP-induced asthma mice as compared with the control group. Furthermore, DiNP-induced asthma group has an increased cardiac caspase-3, Bax, c-Myc and K-ras, and p53 while the Bcl2 decreased when compared with control. Overall, the findings indicate that DiNP-induced asthma impairs cardiac functions by induction of key cardiac oncogenes, downregulation of cardiac energy, transduction of enzymes, and promotion of oxidative stress and cellular death. Graphical abstract: (Figure presented.). Springer 2024-09-17 Article PeerReviewed text en cc_by_nc_nd_4 http://psasir.upm.edu.my/id/eprint/114669/1/114669.pdf Kehinde, Samuel Abiodun and Olajide, Abosede Temitope and Fatokun, Tolulope Peter and Faroud, Dalia and Hadi, Najah R. and Elgazzar, Ahmed M. and James, Adewale Segun and Ashour, Mohamed H. Mazhar (2024) Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model. Naunyn-Schmiedeberg's Archives of Pharmacology. pp. 1-11. ISSN 0028-1298; eISSN: 1432-1912 https://link.springer.com/article/10.1007/s00210-024-03454-4?error=cookies_not_supported&code=f2efed3e-d5a0-40a4-bab5-0079510cc3ff 10.1007/s00210-024-03454-4 |
| spellingShingle | Kehinde, Samuel Abiodun Olajide, Abosede Temitope Fatokun, Tolulope Peter Faroud, Dalia Hadi, Najah R. Elgazzar, Ahmed M. James, Adewale Segun Ashour, Mohamed H. Mazhar Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model |
| title | Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model |
| title_full | Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model |
| title_fullStr | Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model |
| title_full_unstemmed | Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model |
| title_short | Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model |
| title_sort | dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in dinp-induced asthma in murine model |
| url | http://psasir.upm.edu.my/id/eprint/114669/ http://psasir.upm.edu.my/id/eprint/114669/ http://psasir.upm.edu.my/id/eprint/114669/ http://psasir.upm.edu.my/id/eprint/114669/1/114669.pdf |