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The role of GRP78/ATF6/IRE1 and caspase-3/Bax/Bcl2 signaling pathways in the protective effects of gallic acid against cadmiuminduced liver damage in rats     
Yazarlar
Volkan Gelen
Türkiye
Emin Şengül
Türkiye
Serkan Yıldırım
Türkiye
Doç. Dr. İrfan ÇINAR
Kastamonu Üniversitesi, Türkiye
Özet
Objective(s): Cadmium (CD) causes widespread and severe toxic effects on various tissues. Studies have shown that apoptosis, inflammation, and endoplasmic reticulum stress play a role in organ damage caused by CD. Phenolic compounds with strong antioxidant effects are found in various fruits and vegetables. One of these compounds is Gallic acid (GA), which is found both free and hydrolyzable in grapes, pomegranate, tea, hops, and oak bark. Result of various studies show that GA has active antioxidant, anti-inflammatory, and anti-apoptotic properties. In our study, we investigated the mechanism of the protective effect of GA on CD-induced hepatotoxicity in rats. Materials and Methods: In this study, 50 adult male Sprague Dawley rats weighing approximately 200–250 g were used and the rats were divided into 5 groups: Control, CD, GA50+CD, GA100+CD, and GA100. The rats were treated with GA (50 and 100 mg/kg body weight), and Cd (6.5 mg/kg) was administrated to the rats for 5 consecutive days. The liver enzymes, TB levels in serum samples, oxidative stress, inflammation, ER stresses, apoptosis marker, histopathology, 8-OHDG, and caspase-3 positivity were analyzed. Results: CD administration significantly increased liver enzyme levels (AST, ALT, ALP, and LDH), MDA, IL-1-β, IFN-γ, TNF-α, IL-10, IL-6, GRP78, CHOP, ATF6, p -IRE1, sXBP, Bax mRNA expression, Caspase 3, and 8-OHdG expression (P<0.05). These values were found to be significantly lower in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). CD administration significantly decreased the expression levels of TB, IL-4, SOD, GSH, CAT, GPX, and Bcl-2 mRNA (P<0.05). These values were found to be significantly higher in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). Conclusion: The results of the present study indicated that GA prevented Cd-induced hepatic oxidative stress, inflammation, ER stress, apoptosis, and tissue damage in rats.
Anahtar Kelimeler
Apoptosis | Cadmium | Endoplasmic reticulum - stress | Gallic acid | Hepatotoxicity | Inflammation
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı Iranian Journal of Basic Medical Sciences
Dergi ISSN 2008-3866
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q3
Makale Dili İngilizce
Basım Tarihi 09-2023
Cilt No 2023
Sayı 26
Sayfalar 1326 / 1333
Doi Numarası 10.22038/IJBMS.2023.71343.15525
Makale Linki https://www.researchgate.net/profile/Volkan-Gelen/publication/372406232_The_role_of_GRP78ATF6IRE1_and_caspase-3BaxBcl2_signaling_pathways_in_the_protective_effects_of_gallic_acid_against_cadmium-_induced_liver_damage_in_rats/links/64b50eff8de7ed28baa