Dose-Related Gastric Toxicity of Diethyl Phthalate in Female Wistar Rats.

Authors

Gul Sahika Gokdemir, Mehmet Cihan Yavaş, Selim Demirtaş, Fazile Cantürk Tan, Salih Varol, Mehmet Tahir Gokdemir

Published in

Journal of applied toxicology : JAT. Sep 17, 2026. Epub Sep 17, 2026.

Abstract

Diethyl phthalate (DEP) is commonly used in cosmetics, personal care products, and pharmaceutical formulations as a low-molecular-weight phthalate. Despite its widespread use, information on its effects on the gastric mucosa remains limited. This study examined the dose-related effects of DEP on inflammation, oxidative stress, gastric mucosal defense, DNA damage, apoptosis, and histopathological changes in rat gastric tissue. Twenty-eight female Wistar rats were randomly assigned to four groups (n = 7 per group): control and DEP (100, 300, or 600 mg/kg/day). These experimental toxicological doses were administered by oral gavage for 21 days. Gastric tissue levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), superoxide dismutase (SOD), malondialdehyde (MDA), trefoil factor family 1 (TFF1), and mucin-5AC (MUC5AC) were determined by ELISA. Histopathological examination, Bax/Bcl-2 immunohistochemistry, and comet assay were performed. Dose-response relationships were assessed using polynomial trend analysis. DEP exposure resulted in significant dose-dependent increases in IL-6, TNF-α, COX-2, MDA, Bax expression, Bax/Bcl-2 ratio, histopathological damage, and DNA damage (all p < 0.001), whereas SOD levels and Bcl-2 expression significantly decreased (all p < 0.001). TFF1 and MUC5AC levels were significantly increased at 100 mg/kg but significantly decreased at 600 mg/kg compared with controls. Histopathological examination showed progressive gastric mucosal injury with increasing DEP doses. DEP exposure induced dose-related changes in gastric inflammation, oxidative stress, mucosal protective factors, histopathology, DNA damage, and apoptosis-related protein expression. The findings suggest that oxidative stress and inflammation are associated with altered mucosal defense, DNA damage, and apoptosis following DEP exposure.

PMID:
42753078
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

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