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. 2025 Jun 24;9(12):2886-2890.
doi: 10.1182/bloodadvances.2024015038.

Nitrated fatty acids protect against acute kidney injury in sickle cell disease

Mara Carreño  1 , Diane Lenhart  2 , Rajat Pant  2 , Paritosh Mondal  2 , Sonia R Salvatore  3 , Maria F Pires  3 , Enrico M Novelli  2   4 , Francisco J Schopfer  3 , Samit Ghosh  2 , Dario A Vitturi  1
Affiliations

Nitrated fatty acids protect against acute kidney injury in sickle cell disease

Mara Carreño et al. Blood Adv. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: E.M.N. reports being an advisory board member/consultant for Novo Nordisk, Chiesi Pharmaceuticals, and Shield Therapeutics. F.J.S. reports having financial interest in Furanica Inc and Creegh Inc. S.G. reports receiving research funding (not relevant to the current study) from Pfizer Inc as a part of a sponsored research agreement. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Systemic levels of NO2-CLA metabolites are lower in SCD patients. (A-B) Total NO2-CLA and DH-NO2-CLA levels (esterified plus free acid fraction) in healthy (n = 12) and SCD (n = 9) plasma extracts. (C) Representative urine LC-MS/MS chromatograms showing total (top) and isomer-specific NO2-CLA peaks (middle, bottom). (D) Representative traces for the urine NO2-CLA beta-oxidation metabolites NO2-16:2, NO2-14:2 and NO2-12:2. (E-F) Quantification of the total NO2-CLA and its beta-oxidation metabolites in healthy (n = 7) and SCD (n = 6) urine samples. ∗P < .05 by t test (A,B,E) and 2-way analysis of variance (ANOVA) (F) following logarithmic transformation. No statistically significant differences were found between individual urinary NO2-CLA metabolites in the posttest analysis, but 2-way ANOVA identified SCD as a significant contributor to the total data variance in panel F. DH-NO2-CLA, dihydro-NO2-CLA.
Figure 2.
Figure 2.
NO2-OA protects against hemin-induced renal injury in SCD. (A-B) Nrf2-dependent gene expression in HK2 cells treated with NO2-CLA and NO2-OA (n = 3). ∗P < .05, ∗∗P < .001, ∗∗∗P < .0001 by 1-way ANOVA and Dunnett posttest. (C) Protein expression 16 hours after NO2-OA in HK2 cells. (D) DCF oxidation by hemin (8 μM) with or without NO2-OA pretreatment (16 hours). ∗∗∗P < .0001 by 2-way ANOVA. (E) HK2 cell viability 48 hours after 40 μM hemin challenge with or without NO2-OA pretreatment (16 hours) and 10 μM HO-1-IN-1 (n = 7). ∗∗∗P < .0001 by 2-way ANOVA and Dunnett posttest. (E, inset) No effect of HO1-IN-1 on HK2 cell viability. (F) Cytokine production by J774a1 macrophages after 40 μM hemin in the presence or absence of NO2-OA (n = 4-6). ∗P < .05, ∗∗P < .001, ∗∗∗P < .0001 by 1-way ANOVA and Tukey posttest. (G-H) Representative micrographs and quantification of NQO1 and HO1 expression in the kidney of Townes’ SCD mice that received 2.5 mg/kg per day NO2-OA or SO for 3 weeks by oral gavage. Each point is a single field of view from 3 mice per group. The bar represents 100 μm. ∗∗P < .001 by unpaired t test. (I-J) Representative micrographs and apoptotic cell quantification by TUNEL assay in SCD mouse kidney 48 hours after hemin challenge (20 μM/kg IV) in the presence or absence NO2-OA treatment as before. The bar represents 20 μm. ∗∗P < .001 by t test. (K-M) Plasma creatinine, BUN, and urinary KIM-1 levels before and 48 hours after hemin challenge in SCD mice that received vehicle or NO2-OA pretreatment (n = 7-8 per group). ∗P < .05, ∗∗∗P < .0001 by 2-way repeated measures ANOVA and Fisher posttest. BUN, blood urea nitrogen; DCF, 2,7-dichlorodihydrofluorescein diacetate; GCLM, regulatory subunit of glutamate-cysteine ligase; HO1-IN-1, heme oxygenase-1-IN-1; h, hour; KIM-1, kidney injury molecule-1; MCP-1, monocyte chemoattractant protein-1; MFI, mean fluorescence intensity; mRNA, messenger RNA; NQO1, NAD(P)H:quinone dehydrogenase-1; SO, sesame oil vehicle; TNF-α, tumor necrosis factor-α.
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