Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent
10.4196/kjpp.2021.25.5.385
- Author:
Mohamed Sadek ABDEL-BAKKY
1
;
Gouda Kamel HELAL
;
El-Sayed Mohamed EL-SAYED
;
Elham AMIN
;
Abdulmajeed ALQASOUMI
;
Ahmad ALHOWAIL
;
Eman Sayed SAID ABDELMOTI
;
Ahmed Saad SAAD
Author Information
1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt
- Publication Type:Original Article
- From:The Korean Journal of Physiology and Pharmacology
2021;25(5):385-393
- CountryRepublic of Korea
- Language:English
-
Abstract:
Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/ lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in Nacetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.
