Long-term capsaicin diet protects SCD mice from chronic organ damage. (A) Diagram of experimental design. CBC, complete blood count. (B and C) Percentage of aged neutrophils (B) and absolute number of aged neutrophils (C) in peripheral blood of standard diet–treated SCD mice (n = 5) or capsaicin diet–treated SCD mice (n = 5) 4 mo after treatment. (D and E) Plasma ALT (D) and AST (E) concentrations in standard diet–treated SCD mice (n = 5), capsaicin diet–treated SCD mice (n = 5) 4 mo after treatment, and wild-type C57BL/6 mice (n = 5). (F) Quantification of urine osmolality of standard diet–treated SCD mice (n = 4), capsaicin diet–treated SCD mice (n = 4) 14 mo after treatment, genetic SCD mice (n = 6), and wild-type C57BL/6 mice (n = 4). (G) Representative H&E staining of livers from SCD mice fed with standard or capsaicin diet. Note the hemorrhagic necrotic area (blue arrows), steatosis/necrosis (yellow arrow), and leukocyte infiltration (black arrow) in liver sample from a SCD mouse fed with standard chow. Scale bars = 100 µm; 20 µm (inset). (H) Representative H&E staining of kidneys from SCD mice fed with standard chow or capsaicin-containing chow. Note the accumulation of inflammatory cells around glomeruli (glomerulonephritis) in the kidney from SCD mice fed with standard chow (black arrows). Scale bars = 200 µm; 40 µm (inset). Error bars, mean ± SEM; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. Data represent at least two independent experiments analyzed using unpaired Student’s t test in B–E or one-way ANOVA using Tukey’s multiple comparisons test in F. ns, not significant.