UGT1A1 morpholino antisense oligonucleotides produce mild unconjugated hyperbilirubinemia in cyclosporine A-induced cardiovascular disorders in BLC57 mice.
Environ Toxicol Pharmacol
; 104: 104321, 2023 Nov.
Article
en En
| MEDLINE
| ID: mdl-37984676
ABSTRACT
This study aimed to investigate the induction of mild unconjugated hyperbilirubinemia in hepatic UGT1A1 inhibition by Morpholinos antisense in CsA-treated BLC57 mice in comparison with the efficacy of chitosan (CH) as an anti-hypolipidemic natural product. Antisense morpholino oligonucleotides were injected intravenously into CsA-treated mice for 14 days thrice a week. Serum biochemical parameters, antioxidant status, and gene expression analysis of eNOS, PPAR-α, NF-kB, cFn, AT1-R, and ETA-R were determined in cardiac tissues with confirmation by histopathology. Inhibition of UGT1A1 significantly elevated serum unconjugated bilirubin within a physiological range. Furthermore, induced mild hyperbilirubinemia reduces hyperlipidemia, improves antioxidant status, and significantly increases the expression of the cardiac PPAR-α gene while decreasing, ETA-R, iNOS, NF-kB, cFn and AT1-R gene expression in CsA-treated mice. Importantly, mild unconjugated hyperbilirubinemia within physiological ranges may be used as a novel therapeutic strategy to lower hyperlipidemia, atherosclerosis, hypertension, and the CVD outcomes in CsA- treated transplant recipients.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Hiperlipidemias
/
Hipertensión
Límite:
Animals
Idioma:
En
Revista:
Environ Toxicol Pharmacol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Egipto