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Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2020 Nov 16; Vol. 21 (22). Date of Electronic Publication: 2020 Nov 16. - Publication Year :
- 2020
-
Abstract
- The protective effects of alpha-1 antitrypsin (AAT) in tacrolimus (TAC)-induced renal injury was evaluated in a rat model. The TAC group rats were subcutaneously injected with 2 mg/kg TAC every day for four weeks. The TAC with AAT group was cotreated with daily subcutaneous injections of TAC and intraperitoneal injections of AAT (80 mg/kg) for four weeks. The effects of AAT on TAC-induced renal injury were evaluated using serum biochemistry, histopathology, and Western blotting. The TAC injection significantly increased renal interstitial fibrosis, inflammation, and apoptosis as compared to the control treatment. The histopathological examination showed that cotreatment of TAC and AAT attenuated interstitial fibrosis (collagen, fibronectin, and α-SMA staining), and α-SMA expression in Western blotting was also decreased. Immunohistochemical staining for inflammation (osteopontin and ED-1 staining) revealed improved interstitial inflammation in the TAC with AAT group compared to that in the TAC group. The TAC treatment increased renal apoptosis compared to the control treatment, based on the results of increased immunohistochemical staining of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), increased caspase-3 activity, and lower Bcl-2 to Bad expression ratio. However, AAT cotreatment significantly changed these markers and consequently showed decreased apoptosis. AAT protects against TAC-induced renal injury via antifibrotic, anti-inflammatory, and antiapoptotic effects.
- Subjects :
- Animals
Fibrosis
Male
Rats
Rats, Sprague-Dawley
Tacrolimus pharmacology
alpha 1-Antitrypsin
Acute Kidney Injury chemically induced
Acute Kidney Injury metabolism
Acute Kidney Injury pathology
Acute Kidney Injury prevention & control
Anti-Inflammatory Agents pharmacology
Apoptosis drug effects
Gene Expression Regulation drug effects
Tacrolimus adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33207690
- Full Text :
- https://doi.org/10.3390/ijms21228628