Fig 2: Fluorescence microscope images of cisplatin treated renal spheroids. The fluorescence channels show membrane-localized GFP (green) and nephrotoxicity biomarker KIM-1 (red). Scale bars: 100 µm.

Fig 3: Quercetin diminished cell injury and apoptosis in the CI-AKI model via inhibition of HIF-1a on the lncRNA NEAT1/HMGB1 signalling pathway. (A, B) Relative mRNA and protein expression level of HIF-1, lncRNA NEAT1 and HMGB1 in HK-2 cells of Model, M + QC, M + QC + sh NC, M + QC + sh HIF-1a, M + QC + sh NC + HMGB1, and M + QC + sh HIF-1a + HMGB1 group was measured by qRT-PCR and western blotting. HK-2 cells were subjected for the analysis of (C) cell apoptosis rate, (D) Elisa levels of IL-6 and TNF-a, (E) protein expression of IL-6, TNF-a, Kim-1, NAGL, IL-6 and TNF-a between M + QC and M + QC + sh-NC, M + QC + sh-NC and M + QC + sh-HIF-1, M + QC + sh-NC + HMGB1 and M + QC + sh-HIF-1a+ HMGB1 group. The data were expressed as mean ± SD. *p < 0.05, **p < 0.01.

Fig 4: Quercetin diminished cell injury and apoptosis in the CI-AKI model via inhibiting the expression of HIF-1a. (A) HIF-1a was assessed by western blotting in different groups treated with different concentrations of quercetin. (B) Cell survival rate was gradually increased in groups treated with 10, 20, and 30 µM quercetin. (C) Cell apoptosis rate was gradually decreased in model groups with quercetin concentration increased. (D) The expression levels of IL-6 and TNF-a were reduced with quercetin concentration increased in the CI-AKI model. (E) The expression levels of Kim-1, NAGL, IL-6 and TNF-a were decreased with the concentration of quercetin increased. The data were expressed as mean ± SD. *p < 0.05, **p < 0.01.

Fig 5: Physiological and molecular markers of kidney injury. (A) Study protocol. (B) Gross appearance of kidney. (C) Percent survival, animal body weight, and kidney weight. (D) Serum concentration of blood urea nitrogen (BUN), creatinine, and NGAL, as measured by serum ELISA. (E) mRNA expression of KIM-1, TIMP-1, and NGAL in kidney lysates, as measured by qRT-PCR. (F) Urine concentrations of KIM-1, TIMP-1, and NGAL, as measured by urine ELISA. Measurements were taken at day 12. Each group has n = 8 mice, except for survival data for which n = 10 for untreated controls and n = 20 mice for other groups. Significant difference a p < 0.05: relative to untreated control group; b p < 0.05: relative to AKI + IA saline group.