Extended Data Fig. 5: ACMSD inhibitors protect renal function in two different models of AKI.
From: De novo NAD+ synthesis enhances mitochondrial function and improves health
a, Schematic timeline of the cisplatin-induced AKI study. AKI was induced at day 10 after the beginning of the study in male C57BL/6J mice by a single intraperitoneal dose of cisplatin (20 mg kg−1 body weight). Mice in the sham control group were injected with a saline solution. GFR was measured non-invasively 52 h post-cisplatin administration. b–d, Representative photomicrographs of H&E-stained kidney sections (b), histopathological scoring for tubular necrosis (c) and inflammatory cell infiltration (d) of mouse cohorts described in a (sham control, cisplatin-AKI + TES-1025, n = 6; cisplatin-AKI, n = 5 mice). e, Schematic timeline of the IR-AKI study. AKI was induced at day 10 after the beginning of the study in anaesthetized male C57BL/6J mice by a dorsal surgical incision and bilateral occlusion of the renal pedicles for 25 min. Mice in the sham control group underwent the same surgical procedure without application of the occluding clamp on the renal pedicles. f–j, Representative photomicrographs of H&E-stained kidney sections (f) and histopathological scoring for cumulative score (g), tubular necrosis (h), tubular dilation (i), and cast formation (j) of mouse cohorts described in e (n = 5 mice). Tubular cell necrosis (arrows), tubular dilation and casts (asterisk) and interstitial oedema (crescent moon) are indicated on the pictures. k–m, Glutathione protein levels (k), MPO activity (l) and NAD+ content (m) in kidneys of the IR-AKI cohorts described in e (n = 5 mice). n, Protein expression of the respiratory complex subunits in kidneys from the mouse cohorts described in e. The experiment was performed independently twice. Data are mean ± s.e.m. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. P values calculated using two-tailed t-test. For gel source images see Supplementary Fig. 1. For individual P values, see Source Data. The histopathological scoring was performed independently by two pathologists in a blinded manner (b–d, f–j).
