Abstract
Background: Chronic kidney disease and inflammation promote loss of Klotho expression. Given the well-established anti-inflammatory effects of omega-3 fatty acids, we aimed to investigate the effect of fish oil supplementation in a model of CKD. Methods: Male C57BL/6 mice received supplementation with an adenine-enriched diet (AD, n = 5) or standard diet (CTL, n = 5) for 10 days. Two other experimental groups were kept under the adenine diet for 10 days. Following adenine withdrawal on the 11th day, the animals returned to a standard diet supplemented with fish oil (Post AD-Fish oil, n = 9) or not (Post AD-CTL, n = 9) for an additional period of 7 days. Results: Adenine mice exhibited significantly higher mean serum urea, creatinine, and renal expression of the pro-inflammatory markers Interleukin-6 (IL-6), C-X-C motif chemokine 10 (CXCL10), and Interleukin-1β (IL-1β), in addition to prominent renal fibrosis and reduced renal Klotho gene expression compared to the control. Post AD-Fish oil animals demonstrated a significant reduction of IL-6, C-X-C motif chemokine 9 (CXCL9), and IL-1β compared to Post AD-CTL animals. However, serum creatinine, renal fibrosis, and Klotho were not significantly different in the fish oil-treated group. Furthermore, renal histomorphological changes such as tubular dilatation and interstitial infiltration persisted despite treatment. Conclusions: Fish oil supplementation reduced renal pro-inflammatory markers but was not able to restore renal function nor Klotho expression in an adenine-induced CKD model.
Highlights
Inflammation plays a central role in the pathogenesis and progression of chronic kidney disease (CKD)
We investigated whether fish oil, rich in omega-3 fatty acids, increases renal Klotho expression and reduces renal inflammation and fibrosis in a mouse model of inflammatory CKD
Animals fed with adenine for 10 days exhibited higher mean levels of serum creatinine and urea when compared with the control group (Figure 1b,c)
Summary
Inflammation plays a central role in the pathogenesis and progression of chronic kidney disease (CKD). The exogenous administration of TWEAK (Tumor Necrosis Factor-like weak inducer of apoptosis) decreased renal expression of Klotho and the blockade of TWEAK by neutralizing antibodies restored renal expression of Klotho [6]. These data suggest the existence of a bidirectional relationship between Klotho and inflammation. Results: Adenine mice exhibited significantly higher mean serum urea, creatinine, and renal expression of the pro-inflammatory markers Interleukin-6 (IL-6), C-X-C motif chemokine 10 (CXCL10), and Interleukin-1β (IL-1β), in addition to prominent renal fibrosis and reduced renal Klotho gene expression compared to the control. Serum creatinine, renal fibrosis, and Klotho were not significantly different in the fish oil-treated group
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
