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Synthetic and non-synthetic inhibition of ADAM10 and ADAM17 reduces inflammation and oxidative stress in LPS-induced acute kidney injury in male and female mice.
- Source :
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European journal of pharmacology [Eur J Pharmacol] 2024 Nov 15; Vol. 983, pp. 176964. Date of Electronic Publication: 2024 Aug 30. - Publication Year :
- 2024
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Abstract
- Acute kidney injury (AKI) is a severe medical condition that can lead to illness and death. A disintegrin and metalloprotease (ADAM) protein family is a potential treatment target for AKI due to its involvement in inflammation, growth, and differentiation. While ADAM10 and ADAM17 have been identified as significant contributors to inflammation, it is unclear whether they play a critical role in AKI. In this study, we induced AKI in male and female mice using lipopolysaccharide, a bacterial endotoxin that causes inflammation and oxidative stress. The role of kaempferol, which is found in many natural products and known to have antioxidant and anti-inflammatory activity in many pre-clinical studies, was investigated through ADAM10/17 enzymes in AKI. We also investigated the efficacy of a selective synthetic inhibitor named GW280264X for ADAM10/17 inhibition in AKI. Blood urea nitrogen and creatinine levels were measured in serum, while tumor necrosis factor-α, vascular adhesion molecule, interleukin (IL)-1β, glucose regulatory protein-78, IL-10, nuclear factor κ-B, thiobarbituric acid reactive substances, total thiol, ADAM10, and ADAM17 levels were measured in kidney tissue. We also evaluated kidney tissue histologically using hematoxylin and eosin, periodic acid-schiff, and caspase-3 staining. This research demonstrates that GW280264X and kaempferol reduces inflammation and oxidative stress, as evidenced by biochemical and histopathological results in AKI through ADAM10/17 inhibition. These findings suggest that inhibiting ADAM10/17 may be a promising therapeutic approach for treating acute kidney injury.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Female
Male
Mice
Kidney drug effects
Kidney pathology
Kidney metabolism
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents therapeutic use
Kaempferols
Acute Kidney Injury drug therapy
Acute Kidney Injury chemically induced
Acute Kidney Injury pathology
Acute Kidney Injury prevention & control
Acute Kidney Injury metabolism
ADAM17 Protein metabolism
ADAM17 Protein antagonists & inhibitors
Oxidative Stress drug effects
ADAM10 Protein metabolism
ADAM10 Protein antagonists & inhibitors
Lipopolysaccharides
Inflammation drug therapy
Inflammation pathology
Inflammation metabolism
Membrane Proteins metabolism
Membrane Proteins antagonists & inhibitors
Amyloid Precursor Protein Secretases metabolism
Amyloid Precursor Protein Secretases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 983
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 39218341
- Full Text :
- https://doi.org/10.1016/j.ejphar.2024.176964