Administration of α-Galactosylceramide Improves Adenine-Induced Renal Injury

Abstract

Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to >90% of the total population of NKTs and reacts to α-galactosylceramide (αGalCer). αGalCer promotes a complex mixture of Th1 and Th2 cytokines, as interferon (IFN)-γ and interleukin (IL)-4. NKT cells and IFN-γ are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-wk-old C57BL/6j, Jα18KO and IFN-γKO mice. They were fed a 0.25% adenine diet for 10 d. Both adenine-fed wild-type (WT) and Jα18KO mice exhibited renal dysfunction, but adenine-fed Jα18KO mice presented higher expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF)-α and type I collagen. To analyze the role of activated iNKT cells in our model, we administered αGalCer in WT mice during adenine ingestion. After αGalCer injection, we observed a significant reduction in serum creatinine, proinflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-γKO mice after αGalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-γ production is one of the factors contributing to improved renal function after αGalCer administration.

Adenine‐induced chronic kidney disease in rats

“…Using different doses of adenine in mice and rats, this study suggests that mice are more sensitive to adenine than rats. Similar changes were shown with 0.25% adenine for 10 days in the kidneys of C57 BL6 mice …”

“…This treatment prevented functional impairment and structural injuries in the kidney, but no cardiovascular parameters were described. The 0.25% adenine diet was also used as a model for CKD in mice either for 10 days or for 4 weeks . Another study demonstrated similar CKD responses, however, with a higher (0.5%) dose of adenine for 3 weeks which approximates to only 1.5 years in humans .…”

Antioxidant Activity of Spirulina Powder in Male Rate with Adenine–Induced Chronic Renal Failure

“…The existing study accept with other previous studies [15][16][17] . Aguiar et al,(2015) 18 who found rise of kim-1 concentration, in induction chronic renal failure in male rats, also 19,20 , who reported elevation KIM-1 in patients with CRF in humans by comparison with control groups On the other hand, co-administration of spirulina powder with adenine in the present study causes a significant enhancement of the renal function indicators. Our results in coordinate with that reported by Gargouri et al, (2018) 21 who found that spirulina protects neonate rat from leads-induced nephrotoxicity via its antioxidant properties.…”

Roles of Natural Killer T Cells and Natural Killer Cells in Kidney Injury

“…There have also been several studies showing the protective roles of NKT cells in some glomerulonephritis or vasculitis models, and the production of cytokines, such as IL-4, IL-10, and TGF-β was suggested to play various immunoregulatory effects [49,50,51]. The absence of NKT cells exacerbated an experimental model of tubulointerstitial nephritis [52]. In this model, α-GalCer treatment reduced renal injury, suggesting that α-GalCer-induced IFN-γ production contributes to the improvement of renal injury.…”