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ORAL PRESENTATION / SÖZLÜ SUNUM

Methyl Palmitate Attenuates Methotrexate-induced
Hepatotoxicity via Regulating Bax/Caspase-3 Signaling Pathway

Ruhi Turkmen¹ * Yavuz Osman Birdane Orkun Atik Hasan Huseyin Demirel 2
1
,
1

¹Afyon Kocatepe University Faculty of Veterinary Medicine, Departman of Pharmacology
and Toxicology, Afyonkarahisar, TÜRKIYE
2 Afyon Kocatepe University Bayat Vocational School, Afyonkarahisar, TÜRKIYE

*Correspound Author: ruhiturkmen@gmail.com

Oxidative stress, inflammation, and apoptosis are the primary inducers of methotrexate
(MTX)-induced hepatotoxicity. Methyl palmitate (MP) has antioxidant and anti-inflammatory
properties. This study aimed to determine whether MP can provide protection against MTX-
induced hepatotoxicity. For this purpose, 24 female rats were divided into 4 different groups,
each consisting of six animals (n=6). The control group; MTX (20 mg/kg) group; MP (300 mg/kg)
group; and MP+MTX (300 mg/kg+20 mg/kg) group. On day 29, the rats were sacrificed, and
blood samples and liver tissue were collected. Blood and liver tissue were analyzed for certain
oxidant-antioxidant parameters, including malondialdehyde (MDA), reduced glutathione (GSH),
superoxide dismutase (SOD), and catalase (CAT). Liver tissue 8-hydroxy-2′-deoxyguanosine (8-
OhdG) levels were measured by ELISA. Serum samples were analyzed for certain liver function
parameters (aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine
aminotransferase (ALT), total bilirubin, albumin, lactate dehydrogenase (LDH), and total protein)
using commercial kits. Inflammation markers in liver tissue, including interleukin-10 (IL-10),
interleukin-6 (IL-6), B-cell lymphoma-3 (Bcl-3), cyclooxygenase-2/prostaglandin endoperoxide
synthase 2 (COX-2), and prostaglandin E2 (PGE2) levels were measured using ELISA. Western
blot analysis was performed to detect the protein expression of genes related to the Bax and
caspase-3 pathways in rat liver tissue, while structural damage was examined using light
microscopy. Compared to the control group, there was a significant increase in serum and liver
MDA levels and a significant decrease in GSH levels and SOD and CAT activities in the MTX group.
In addition, 8-OhdG levels were higher in the MTX group than in the control group. Serum AST,
ALP, ALT, total bilirubin, and LDH levels were significantly increased in MTX-treated rats
compared to the control group, while serum albumin and total protein levels were significantly
decreased compared to the control group. Compared to the control group, there was a significant
increase in Bcl-3, COX-2, PGE-2, and IL-6 levels in the liver tissue homogenate of rats given MTX,
and a significant decrease in IL-10 levels, an anti-inflammatory marker. It was determined that
MTX administration caused histopathological changes in rat liver tissues and led to a significant
increase in apoptotic protein (Bax and caspase-3) levels. It was found that MP applications
brought the above-mentioned parameters closer to control group levels. Our findings support the
potential use of MP to prevent and treat MTX-induced hepatotoxicity.
Keywords: Oxidative stress, Inflammation, Western Blot, 8-OhdG.

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