This preprint is under consideration at Naunyn-Schmiedeberg's Archives of Pharmacology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research Article
Mona Elhadidy
Mansoura University Faculty of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8002-7478
License:
This work is licensed under a CC BY 4.0 License. Read Full License
purpose: Busulfan is an antineoplastic drug that produces pulmonary fibrosis. This study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats.
Methods: Twenty-four adult male rats were divided into four groups: control, α-lipoic acid (ALA), busulfan, and busulfan plus α-lipoic acid. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically. The pulmonary expression of COX-2 and NOX-4 mRNA were assessed using qRT-PCR.
Results: administration of ALA significantly ameliorated BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues. Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4.
Conclusion: ALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.
Keywords
Busulfan, Pulmonary fibrosis, α-lipoic acid (ALA), apoptosis, COX-2, NOX-4
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Posted 18 Mar, 2021
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This preprint is under consideration at Naunyn-Schmiedeberg's Archives of Pharmacology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Mona Elhadidy
Mansoura University Faculty of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8002-7478
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 18 Mar, 2021
No community comments so far
Reviewers invited
Invitations sent on 15 Mar, 2021
Review #? received
Received 15 Mar, 2021
Editor assigned
On 14 Mar, 2021
First submitted
On 10 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Clinical Pharmacology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
purpose: Busulfan is an antineoplastic drug that produces pulmonary fibrosis. This study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats.
Methods: Twenty-four adult male rats were divided into four groups: control, α-lipoic acid (ALA), busulfan, and busulfan plus α-lipoic acid. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically. The pulmonary expression of COX-2 and NOX-4 mRNA were assessed using qRT-PCR.
Results: administration of ALA significantly ameliorated BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues. Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4.
Conclusion: ALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
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