A triterpenoid (corosolic acid) ameliorated AOM-mediated aberrant crypt foci in rats: modulation of Bax/PCNA, antioxidant and inflammatory mechanisms
الباحث الأول:
Morteta H. Al-Medhtiy
الباحثين الآخرين:
Mohammed T Mohammed, Mohammed M. Hussein M. Raouf, Ayman M. Al-Qaaneh, Ahmed A.j. Jabbar, Fuad Othman Abdullah, Ramzi A. Mothana, Abdullah R. Alanzi, Rawaz Rizgar Hassan, Mahmood Ameen Abdulla, Musher Ismail saleh & Sidgi Hasson
المجلة:
Journal of Molecular Histology
تاريخ النشر:
10 أغسطس، 2024
مختصر البحث:
Abstract
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 chemopr…
Abstract
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.
