Geraniol activates Nrf-2/HO-1 signaling pathway mediating protection against oxidative stress-induced apoptosis in hepat
- PDF / 4,533,192 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 87 Downloads / 197 Views
ORIGINAL ARTICLE
Geraniol activates Nrf-2/HO-1 signaling pathway mediating protection against oxidative stress-induced apoptosis in hepatic ischemia-reperfusion injury Soad Z. El-Emam 1 & Ayman A. Soubh 2 & Asmaa K. Al-Mokaddem 3 & Dina M. Abo El-Ella 1 Received: 27 January 2020 / Accepted: 28 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Geraniol (GOH) is a natural essential oil that possesses antioxidant, anti-inflammatory, and antiapoptotic properties by various signaling pathways. Liver ischemia-reperfusion injury (IRI) is a serious event that triggers liver dysfunction or even failure. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcriptional factor, maintains cellular defense mechanism through antioxidant and anti-inflammatory properties. To detect GOH effect against liver IRI through the activation of the Nrf2/HO-1 antioxidant pathway, five groups of rats were randomized to normal, sham, IR, GOH, and GOH/IR. Blood samples and liver tissues were collected to measure various biochemical parameters related to liver function, and oxidative stress as well as inflammatory and apoptotic indicators besides liver tissue histopathology was evaluated by light microscopy. GOH induces activation of Nrf2 along with the upregulation of HO-1 expression. Also, the antioxidant activity of GOH was shown by the elevation of total antioxidant capacity and GSH levels, together with normalizing malondialdehyde. Regarding the antiinflammatory effect of GOH, it suppresses the levels of TNF-α, iNOS, and COX-2. Additionally, the antiapoptotic effect of GOH, Bax, and caspase-3, 9 were reduced in liver tissue. GOH is a promising hepatoprotective agent in liver IRI through the activation of Nrf2/HO-1 antioxidant pathway. Keywords Liver ischemia-reperfusion . Nrf2/HO-1 antioxidant pathway . Geraniol . Caspase-3 . Inducible nitric oxide synthase . Cyclooxygenase-2
Abbreviations IRI Ischemia-reperfusion injury Nrf2 Nuclear factor erythroid 2-related factor 2 GOH Geraniol ALT Alanine aminotransferase AST Aspartate aminotransferase TAC Total antioxidant capacity MDA Malondialdehyde GSH Reduced glutathione
* Dina M. Abo El-Ella [email protected] 1
Department of Pharmacology and Toxicology, Faculty of Pharmacy, October 6 University, 6th of October City, Giza 12566, Egypt
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy, ACU University, 4th Industrial Zone, Banks Complex, 6th of October City, Giza 12451, Egypt
3
Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt
TNF-α iNOS COX-2 HO-1
Tumor necrosis factor-alpha Inducible nitric oxide synthase Cyclooxygenase-2 Hemeoxygenase-1
Introduction Disturbance of hepatic blood supply to reduce blood loss during liver transplantation and hepatic resection causes liver ischemia with subsequent reperfusion injury in the hepatocytes. Liver IRI is a serious postsurgical complication accompanied by a high mortality rate (Kudoh et al. 2014). On the molecular level, several interrelating facto
Data Loading...
