Abatement of acrylonitrile-induced gastric injury by 2-Methoxyestradiol through inhibition of TLR4/MYD88/phospho-p38 MAPK axis.

Acrylonitrile (ACN) is a widely used industrial chemical. It has a wide range of toxicities, including gastric mucosal damage. 2-Methoxyestradiol (2ME) is one of the estrogen metabolites with a plethora of beneficial pharmacological activities. This study aimed to evaluate the possible preventive effects of 2ME against ACN-induced gastric injury in rats. 2ME was injected intraperitoneally into rats at two dose levels (1 and 5 mg/kg) prior to a single oral dose of ACN (30 mg/kg). 2ME obviously prevented histopathological alteration in gastric tissues. 2ME prevented ACN-induced oxidative damage as shown by preventing malondialdehyde (MDA) accumulation and superoxide dismutase (SOD) and catalase (CAT) exhaustion. Also, it prevented ACN-induced increase in the immuno-expression of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-κB). 2ME modulated ACN-induced changes in B-cell lymphoma 2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) expression, opposing apoptotic death of gastric tissues. Finally, 2ME inhibited ACN-induced enhancement of toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MYD88), and phosphorylated p38 mitogen-activated protein kinase (phospho-p38 MAPK) immuno-expression. Conclusively, 2ME ameliorates ACN-induced gastric injury. This protective effect may be associated with the antioxidant, anti-inflammatory, and anti-apoptotic properties of 2ME, in addition to a potential modulation of the TLR4/MYD88/phospho-p38 MAPK signaling pathway.