A1 Refereed original research article in a scientific journal
Dietary docosahexaenoic acid plays an opposed role in ferroptotic and non-ferroptotic acute kidney injury
Authors: Shan Kai, Li Jiaqi, Yang Qin, Chen Kang, Zhou Shanshan, Jia Lingling, Fu Guoling, Qi Yumin, Wang Qizai, Chen Yong Q.
Publisher: ELSEVIER SCIENCE INC
Publication year: 2023
Journal: Journal of Nutritional Biochemistry
Journal name in source: JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Journal acronym: J NUTR BIOCHEM
Article number: 109418
Volume: 120
Number of pages: 13
ISSN: 0955-2863
eISSN: 1873-4847
DOI: https://doi.org/10.1016/j.jnutbio.2023.109418(external)
Web address : https://doi.org/10.1016/j.jnutbio.2023.109418(external)
Abstract
Ferroptosis due to polyunsaturated fatty acid (PUFA) peroxidation has been implicated in the pathogenesis of acute kidney injury (AKI), suggesting the risk of dietary intake of PUFA for people susceptible to AKI. Clinically, however, in addition to ferroptosis, other mechanisms also contribute to different types of AKI such as inflammation associated necroptosis and pyroptosis. Therefore, the role of PUFA, especially & omega;3 PUFA which is a common food supple-ment, in various AKIs deserves further evaluation. In this study, rhabdomyolysis-and folic acid-induced AKI (Rha-AKI and FA-AKI) were established in mice fed with different fatty acids Histology of kidney, blood urea nitrogen and creatinine, lipid peroxidation, and inflammatory factors were examined. Results showed that these two types of AKIs had diametrically different pathogenesis indicated by that ferrostatin-1 (Fer-1), a lipid antioxidant, can attenuate FA-AKI rather than Rha-AKI. Further, dietary DHA (provided by fish oil) reduced tubular injury and renal lesion by inhibiting peroxidation and inflammation in mice with Rha-AKI while increasing cell death, tissue damage, peroxidation and inflammation in mice with FA-AKI. In human renal tubular epithelial cell line HK-2, MTT assay and DHE staining showed that both myoglobin and ferroptosis inducers can cause cell death and oxidative stress. Ferroptosis inducer-induced cell death was promoted by DHA, while such result was not observed in myoglobin-induced cell death when adding DHA. This study illus-trates that the mechanisms of AKI might be either ferroptosis dependent or -independent and the deterioration effect of dietary DHA depends on whether ferroptosis is involved.& COPY; 2023 Published by Elsevier Inc.
Ferroptosis due to polyunsaturated fatty acid (PUFA) peroxidation has been implicated in the pathogenesis of acute kidney injury (AKI), suggesting the risk of dietary intake of PUFA for people susceptible to AKI. Clinically, however, in addition to ferroptosis, other mechanisms also contribute to different types of AKI such as inflammation associated necroptosis and pyroptosis. Therefore, the role of PUFA, especially & omega;3 PUFA which is a common food supple-ment, in various AKIs deserves further evaluation. In this study, rhabdomyolysis-and folic acid-induced AKI (Rha-AKI and FA-AKI) were established in mice fed with different fatty acids Histology of kidney, blood urea nitrogen and creatinine, lipid peroxidation, and inflammatory factors were examined. Results showed that these two types of AKIs had diametrically different pathogenesis indicated by that ferrostatin-1 (Fer-1), a lipid antioxidant, can attenuate FA-AKI rather than Rha-AKI. Further, dietary DHA (provided by fish oil) reduced tubular injury and renal lesion by inhibiting peroxidation and inflammation in mice with Rha-AKI while increasing cell death, tissue damage, peroxidation and inflammation in mice with FA-AKI. In human renal tubular epithelial cell line HK-2, MTT assay and DHE staining showed that both myoglobin and ferroptosis inducers can cause cell death and oxidative stress. Ferroptosis inducer-induced cell death was promoted by DHA, while such result was not observed in myoglobin-induced cell death when adding DHA. This study illus-trates that the mechanisms of AKI might be either ferroptosis dependent or -independent and the deterioration effect of dietary DHA depends on whether ferroptosis is involved.& COPY; 2023 Published by Elsevier Inc.
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