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. 2022 Jun 27;19(7):1138-1146.
doi: 10.7150/ijms.72646. eCollection 2022.

Curcumin enhances p-cresyl sulfate-induced cytotoxic effects on renal tubular cells

Chyou-Wei Wei  1 , Tsai-Kun Wu  2   3 , Shu-Cing Wu  1 , Yi-Lin Chen  4   5 , Ying-Ru Pan  6 , Yi-Chung Chien  7   8   9   10 , Jia-Yan Wu  7   8   9   10 , Yung-Lung Yu  7   8   9   10   11 , Giou-Teng Yiang  12   13
Affiliations

Curcumin enhances p-cresyl sulfate-induced cytotoxic effects on renal tubular cells

Chyou-Wei Wei et al. Int J Med Sci. .

Abstract

Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, can induce oxidative stress and cause renal disease progression. However, the different cytotoxic effects on renal cells between IS and PCS are not stated. Due to uremic toxins are generally found in CKD patients, the mechanisms of uremic toxins-induced renal injury are required to study. Curcumin has anti-oxidant, anti-inflammatory and anti-apoptotic effects which may be potential used to protect against renal damage. In contrast, curcumin also exert cytotoxic effects on various cells. In addition, curcumin may reduce or enhance cytotoxicity combined with different chemicals treatments. However, whether curcumin may influence uremic toxins-induced renal injury is unclear. The goal of this study is to compare the different cytotoxic effects on renal cells between IS and PCS treatment, as well as the synergistic or antagonistic effects by combination treatments with curcumin and PCS. Our experimental result shows the PCS exerts a stronger antiproliferative effect on renal tubular cells than IS treatment. In addition, our study firstly demonstrates that curcumin enhances PCS-induced cell cytotoxicity through caspase-dependent apoptotic pathway and cell cycle alteration.

Keywords: Curcumin; Indoxyl sulfate; p-cresyl sulfate.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Cell survival rate of NRK-52E cells by PCS and IS treatments. (A) Cells were treated with 100 µM PCS or 100 µM IS. (B) Cells were treated with 200 µM PCS or 200 µM IS (C) Cells were treated with 500 µM PCS or 500 µM IS. Cell survival rates were determined at 24-96 hours by MTT assay and calculated as A570 experimental group/A570 control group × 100%. The data were calculated from four independent experiments and presented as mean ± SD. *P < 0.05.
Figure 2
Figure 2
Cell survival rate of HK-2 cells by PCS and curcumin treatments. (A) Cells were treated with 100, 200, and 500 µM PCS. (B) Cells were treated with 8 µM curcumin. Cell survival rates were determined at 24-96 hours by MTT assay and calculated as A570 experimental group/A570 control group × 100%. The data were calculated from four independent experiments and presented as mean ± SD. *P < 0.05.
Figure 3
Figure 3
Cell survival rate of HK-2 cells by PCS, curcumin, and PCS plus curcumin treatments. (A) Cells were treated with 100µM PCS, 8 µM curcumin and 100µM PCS plus 8 µM curcumin. (B) Cells were treated with 200 µM PCS, 8 µM curcumin and 200 µM PCS plus 8 µM curcumin. (C) Cells were treated with 500 µM PCS, 8 µM curcumin and 500 µM PCS plus 8 µM curcumin. Cell survival rates were determined at 24-96 hours by MTT assay and calculated as A570 experimental group/A570 control group × 100%. The data were calculated from four independent experiments and presented as mean ± SD. *P < 0.05.
Figure 4
Figure 4
The percentage of G0/G1, S, and G2/M phase was indicated on HK-2 cells. (A) Control cells. (B) Cells were treated with 100µM PCS. (C) Cells were treated with 200 µM PCS. (D) Cells were treated with 8 µM curcumin. (E) Cells were treated with 100 µM PCS plus 8 µM curcumin. (F) Cells were treated with 200 µM PCS plus 8 µM curcumin.100 µM PCS. The cell cycle was analyzed by using flow cytometry at 48 hour.
Figure 5
Figure 5
The percentage of sub-G1 phase was indicated on HK-2 cells. (A) Control cells. (B) Cells were treated with 100 µM PCS. (C) Cells were treated with 200µM PCS. (D) Cells were treated with 8 µM curcumin. (E) Cells were treated with 100µM PCS plus 8 µM curcumin. (F) Cells were treated with 200 µM PCS plus 8 µM curcumin.100 µM PCS. The cell cycle was analyzed by using flow cytometry at 48 hour.
Figure 6
Figure 6
The levels of caspase-3 and cleaved PARP. (A) Caspase-3, cleaved caspase-3 and cleaved PARP were assayed by western blot. (B) Cleaved PARP/tubulin intensity ratio was calculated. (C) Cleaved caspase-3/caspase-3 intensity ratio was calculated. The proteins were determined after 48 hours treatments on control group (lane 1 and bar1), 100 µM PCS-treated group (lane 2 and bar 2), 100 µM PCS-treated group (lane 3 and bar 3), 200 µM PCS-treated group (lane3 and bar3), 8 µM curcumin-treated group (lane4 and bar 4), 100 µM PCS plus 8 µM curcumin-treated group (lane 5 and bar 5), 200 µM PCS plus 8 µM curcumin-treated group (lane6 and bar6). The data were determined from three independent experiments and presented as mean ± SD. *P < 0.05.
Figure 7
Figure 7
Schematic illustration depicting the roles of curcumin enhances p-cresyl sulfate-induced cytotoxic effects on renal tubular cells.
See this image and copyright information in PMC

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