Abstract
Therapeutic effect of non-steroidal anti-inflammatory drugs (NSAIDs) has been related with gastrointestinal injury. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), can prevent gastric and small intestinal damage. Nonetheless, contribution of antioxidative action in the protective effect of DHA has not been evaluated before in the small intestine injury after indomethacin treatment. Pathogenesis of NSAID-induced small intestinal injury is multifactorial, and reactive oxidative species have been related to indomethacin’s small intestinal damage. The present work aimed to evaluate antioxidative activity in the protective action of DHA in the indomethacin-induced small intestinal damage. Female Wistar rats were gavage with DHA (3 mg/kg) or omeprazole (3 mg/kg) for 10 days. Each rat received indomethacin (3 mg/kg, orally) daily to induce small intestinal damage. The total area of intestinal ulcers and histopathological analysis were performed. In DHA-treated rats, myeloperoxidase and superoxide dismutase activity, glutathione, malondialdehyde, leukotriene, and lipopolysaccharide (LPS) levels were measured. Furthermore, the relative abundance of selective bacteria was assessed. DHA administration (3 mg/kg, p.o.) caused a significant decrease in indomethacin-induced small intestinal injury in Wistar rats after 10 days of treatment. DHA’s enteroprotection resulted from the prevention of an increase in myeloperoxidase activity, and lipoperoxidation, as well as an improvement in the antioxidant defenses, such as glutathione levels and superoxide dismutase activity in the small intestine. Furthermore, we showed that DHA’s enteroprotective effect decreased significantly LPS levels in indomethacin-induced injury in small intestine. Our data suggest that DHA’s enteroprotective might be attributed to the prevention of oxidative stress.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
Martha Ivonne Sánchez Trigueros is a CONACyT, Mexico fellow (Grant Number 781715). Authors acknowledge to Q.F.B. Martha Patricia González García from Pharmacology Deparment-Cinvestav, M.V.Z. Ricardo Gaxiola Centeno, M.V.Z. Benjamín Chávez Álvarez, M.V.Z. Carlos Giovanni Sam Miranda from UPEAL-Cinvestav for their technical assistance in this project.
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Financial support was provided by Consejo Nacional de Ciencia y Tecnología (CONACyT Project 285416) and SIP, Mexico 20220896.
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MIST conducted all experiments and wrote the draft. EAPP, GC, and AECP analyzed the data. EAP contributed to the experiments presented in Tables 1 and 2. CPC contributed to the design of the experiments performed in Figs. 4 and 5. IMV and DC contributed to the experiments conducted for Fig. 5. AECP wrote the final draft, supervised the research, and edited the manuscript. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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The study was evaluated and approved by the Bioethics Committee of Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Mexico City, México (registration number: CBE/021/2019).
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Sánchez-Trigueros, M.I., Martínez-Vieyra, I.A., Pineda-Peña, E.A. et al. Role of antioxidative activity in the docosahexaenoic acid’s enteroprotective effect in the indomethacin-induced small intestinal injury model. Naunyn-Schmiedeberg's Arch Pharmacol (2023). https://doi.org/10.1007/s00210-023-02881-z
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DOI: https://doi.org/10.1007/s00210-023-02881-z