Liver protective effects of renin-angiotensin system inhibition have no survival benefits in hepatocellular carcinoma induced by repetitive administration of diethylnitrosamine in mice

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Saber S.; Mahmoud A.; Helal N.; El-Ahwany E.; Abdelghany R.

Journal: Open Access Macedonian Journal of Medical Sciences

Publisher: Open Access Macedonian Journal of Medical Sciences

Publication Date: 6 June 2018

Volume / Issue: Volume 6 / Issue 6

Pages: 955–960

ISSN: 18579655

DOI: 10.3889/oamjms.2018.167

Scopus: View on Scopus

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Saber S., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Mahmoud A., Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; Helal N., Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt; El-Ahwany E., Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt; Abdelghany R., Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt

Abstract

BACKGROUND: Preclinical studies have demonstrated that renin-angiotensin system (RAS) signalling has strong tumour-promoting effects and RAS inhibition was associated with improvement in the overall survival in some cancer types including hepatocellular carcinoma (HCC). OBJECTIVE: We aimed to investigate the effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II-receptor blockers (ARBs) on the survival of mice with diethylnitrosamine (DEN) induced HCC. METHODS: HCC was induced by weekly i.p. administration of DEN. Mice were treated with sorafenib (SO) (30 mg/kg), perindopril (PE) (1 mg/kg), fosinopril (FO) (2 mg/kg), losartan (LO) (10 mg/kg), PE (1 mg/kg) + SO (30 mg/kg), FO (2 mg/kg) + SO (30 mg/kg), or LO (10 mg/kg) + SO (30 mg/kg). Survival analysis was done using the Kaplan-Meier method, and the log-rank test was used for assessing the significance of difference between groups. RESULTS: The administration of PE, FO and LO as monotherapy or as combined with SO resulted in marked improvement in the liver histologic picture with no impact on overall survival of mice. CONCLUSION: Interfering the RAS either through the inhibition of ACE or the blockade of angiotensin II type 1 (AT1) receptors has similar effects on the liver of DEN-induced HCC mice and is not associated with longer survival due to detrimental effects of DEN on other organs. Hence, repetitive administration of DEN in such models of HCC is not suitable for mortality assessment studies. © 2018 Sameh Saber, Amr Mahmoud, Noha Helal, Eman El-Ahwany, Rasha Abdelghany.

Keywords

Diethylnitrosamine; Hepatocellular carcinoma; Renin-angiotensin system; Survival analysis; angiotensin receptor antagonist; dipeptidyl carboxypeptidase inhibitor; fosinopril; losartan; perindopril; sorafenib; animal experiment; animal model; animal tissue; Article; controlled study; liver cell carcinoma; liver protection; male; monotherapy; mouse; nonhuman; overall survival; renin angiotensin aldosterone system; repeated drug dose

Citation Information

Scopus Citations: 28

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