Modulatory effect of Persea Americana oil against diethylnitrosamine-induced hepatotoxicity in rats: a proposed mechanism

• Published in: Bulletin of the National Research Centre Vol. 45; no. 1; pp. 1 - 10
• Main Authors: Abozaid, Omayma A. R., Anees, Lobna M., Abdel-Hamed, Gehan R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 14-11-2021; Springer Nature B.V; SpringerOpen
• Subjects: Apoptosis; Apoptotic biomarkers; Bcl-2 protein; Biomarkers; Caspase-3; Diethylnitrosamine; Gene expression; Hepatotoxicity; Humanities and Social Sciences; iNOS; Liver; Mitochondria; Molecular Biology and Biotechnology; multidisciplinary; NAD(P)H oxidase; NADPH oxidase; Nitric oxide; Nitric-oxide synthase; Oral administration; Oxidase; PARP-1; Persea; Persea Americana (avocado) oil; Poly(ADP-ribose) polymerase; Ribose; Science; Science (multidisciplinary); iNOS; Apoptotic biomarkers; Hepatotoxicity; PARP-1; NADPH oxidase; Persea Americana (avocado) oil
• ISSN: 2522-8307; 2522-8307
• DOI: 10.1186/s42269-021-00653-4

Background
The purpose of this study was to investigate the effectiveness of Persea Americana (avocado) oil against diethylnitrosamine (DEN)-induced hepatotoxicity in rats.
Methods
For the induction of hepatotoxicity, DEN was administrated orally in a dose of 20 mg/kg B.wt for 6 successive weeks, and then the animals were gavaged with Persea Americana oil in a dose of 4 mL/kg b.wt. daily for another 6 weeks. Serum caspase-3 activity and poly (ADP-ribose) polymerase-1 (PARP-1) levels were estimated; in addition to gene expressions for NADPH oxidase, inducible nitric oxide synthase (iNOS), Bcl-2, and Bax were detected.
Results
The DEN-intoxicated group exhibited a remarkable increase in NADPH oxidase and iNOS expression combined with over-activation of PARP-1 and increased antiapoptotic Bcl-2 gene expression, whereas the expression of apoptotic biomarkers significantly decreased. On the other hand, treatment with Persea Americana oil significantly suppressed the elevated levels of hepatic enzymes and improved histopathological alterations in the liver. Furthermore, these groups displayed marked downregulation in NADPH oxidase and iNOS expressions. Persea Americana oil suppressed the expression of the antiapoptotic Bcl-2, activated the intrinsic mitochondrial apoptosis pathway through upregulation of pro-apoptotic Bax, and induced an obvious increase in caspase-3 activity. Moreover, Persea Americana oil administration markedly inhibited the activity of PARP-1.
Conclusions
This study indicated the promising potential of Persea Americana oil against DEN-induced hepatic injury through its anti-oxidative activity and pro-apoptotic effect via caspase activation and PARP-1 inhibition.