A triterpenoid (corosolic acid) ameliorated AOM-mediated aberrant crypt foci in rats: modulation of Bax/PCNA, antioxidant and inflammatory mechanisms.

Autor: Al-Medhtiy MH; Department of Anatomy and Histology, Faculty of Veterinary Medicine, University of Kufa, Kufa, Najaf Region, 540011, Iraq., Mohammed MT; Department of Microbiology, Faculty of veterinary medicine, University of Kufa, Kufa, Iraq., M Raouf MMH; Department of Biomedical Sciences, College of Applied Science, Cihan University-Erbil, Erbil, Kurdistan Region, 44001, Iraq., Al-Qaaneh AM; Department of Allied Health Sciences, Al-Balqa Applied University (BAU), Al-Salt, 19117, Jordan., Jabbar AAJ; Department of Medical Laboratory Technology, Erbil Technical Health and Medical College, Erbil Polytechnic University, Erbil, 44001, Iraq. ahmed.abuljabbar@epu.edu.iq., Abdullah FO; Department of Chemistry, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq., Mothana RA; Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia., Alanzi AR; Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia., Hassan RR; Department of Medical Laboratory Science, College of Science, Knowledge University, Kirkuk Road, Erbil, 44001, Iraq., Abdulla MA; Department of Medical Analysis, Faculty of Applied Science, Tishk International University, Erbil, Iraq., Saleh MI; Department of Chemistry, Faculty of Science and Health, Koya University, Koya KOY45, Kurdistan Region, Erbil, 44001, Iraq., Hasson S; School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK.
Jazyk: angličtina
Zdroj: Journal of molecular histology [J Mol Histol] 2024 Oct; Vol. 55 (5), pp. 765-783. Date of Electronic Publication: 2024 Aug 10.
DOI: 10.1007/s10735-024-10229-x
Abstrakt: Corosolic acid (CA) is a well-known natural pentacyclic triterpene found in numerous therapeutic plants that can exhibit many bioactivities including anti-inflammatory and anti-tumor actions. The current investigation explores the chemoprotective roles of CA against azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty Sprague Dawley rats were grouped in 5 cages; Group A, normal control rats inoculated subcutaneously (sc) with two doses of normal saline and fed orally on 10% tween 20; Groups B-E received two doses (sc) of azoxymethane in two weeks and treated with either 10% tween 20 (group B) or two intraperitoneal injections of 35 mg/kg 5-fluorouracil each week for one month (group C), while group D and E treated with 30 and 60 mg/kg, respectively, for 2 months. The toxicity results showed lack of any behavioral abnormalities or mortality in rats ingested with up-to 500 mg/kg of CA. The present AOM induction caused a significant initiation of ACF characterized by an increased number, larger in size, and well-matured tissue clusters in cancer controls. AOM inoculation created a bizarrely elongated nucleus, and strained cells, and significantly lowered the submucosal glands in colon tissues of cancer controls compared to 5-FU or CA-treated rats. CA treatment led to significant suppression of ACF incidence, which could be mediated by its modulatory effects on the immunohistochemical proteins (pro-apoptotic (Bax) and reduced PCNA protein expressions in colon tissues). Moreover, CA-treated rats had improved oxidative stress-mediated cytotoxicity indicated by increased endogenous antioxidants (SOD and CAT) and reduced lipid peroxidation indicators (MDA). In addition, CA ingestion (30 and 60 mg/kg) suppressed the inflammatory cascades, indicated by decreased serum TNF-α and IL-6 cytokines and increased anti-inflammatory (IL-10) cytokines consequently preventing further tumor development. CA treatment maintained liver and kidney functions in rats exposed to AOM cytotoxicity. CA could be a viable alternative for the treatment of oxidative-related human disorders including ACF.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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