Fenretinide inhibits macrophage inflammatory mediators and controls hypertension in spontaneously hypertensive rats via the peroxisome proliferator-activated receptor gamma pathway

Figures & data

Figure 1 Fenretinide increased the expression of PPARγ in RAW264.3 macrophages.

Notes: (A) RAW264.7 cells were treated with various doses of LPS, as indicated, for 24 hours. (B) Cells were pretreated with the indicated doses of fenretinide for 1 hour, and then treated with 1 μg/mL LPS for another 24 hours. (C) Cells were pretreated with GW9662 at the indicated doses for 30 minutes, and 10 μM fenretinide was then added to the culture medium for another 30 minutes. LPS (1 μg/mL) was further added to the cells for 24 hours. At the end of the experiments, the cells were harvested and lysed for the determination of PPARγ expression. The data are expressed as mean ± SEM and obtained from three individual experiments. *P<0.05; **P<0.01; ***P<0.001 as compared with the control group. ^#P<0.05; ^##P<0.01; ^###P<0.001 as compared with the LPS-treated group.
Abbreviations: FEN, fenretinide; LPS, lipopolysaccharide; PPARγ, peroxisome proliferator-activated receptor gamma; SEM, standard error of the mean; GW, GW9662.

Figure 2 Fenretinide inhibited LPS-induced inflammatory mediators through PPARγ pathway.

Notes: (A) RAW264.7 cells were treated with various doses of LPS, as indicated, for 24 hours. (B) Cells were pretreated with the indicated doses of fenretinide for 1 hour, and then treated with 1 μg/mL LPS for another 24 hours. (C) Cells were pretreated with GW9662 at the indicated doses for 30 minutes, and 10 μM fenretinide was then added to the culture medium for another 30 minutes. LPS (1 μg/mL) was further added to the cells for 24 hours. At the end of the experiments, the culture medium was collected for the determination of TNF-α, IL-6, and MCP-1 by enzyme-linked immunosorbent assay kits. The data are expressed as mean ± SEM and obtained from three individual experiments. *P<0.05; **P<0.01; ***P<0.001 as compared with the control group. ^#P<0.05; ^##P<0.01; ^###P<0.001 as compared with the LPS-treated group. Abbreviations: FEN, fenretinide; LPS, lipopolysaccharide; IL-6, interleukin 6; MCP-1, monocyte chemoattractant protein; PPARγ, peroxisome proliferator-activated receptor gamma; TNF-α, tumor necrosis factor alpha; SEM, standard error of the mean; GW, GW9662.

Figure 3 Fenretinide inhibited LPS-induced iNOS expression PPARγ pathway.

Notes: (A) RAW264.7 cells were treated with various doses of LPS, as indicated, for 24 hours. (B) Cells were pretreated with the indicated doses of fenretinide for 1 hour, and then treated with 1 μg/mL LPS for another 24 hours. (C) Cells were pretreated with GW9662 at the indicated doses for 30 minutes, and 10 μM fenretinide was then added to the culture medium for another 30 minutes. LPS (1 μg/mL) was further added to the cells for 24 hours. At the end of the experiments, the cells were harvested and lysed for the determination of iNOS expression. The data are expressed as mean ± SEM and obtained from three individual experiments. *P<0.05; **P<0.01; ***P<0.001 as compared with the control group. ^#P<0.05; ^##P<0.01; ^###P<0.001 as compared with the LPS-treated group.
Abbreviations: FEN, fenretinide; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; PPARγ, peroxisome proliferator-activated receptor gamma; SEM, standard error of the mean; GW, GW9662.

Figure 4 Fenretinide inhibited LPS-induced NO production through PPARγ pathway.

Notes: (A) RAW264.7 cells were treated with various doses of LPS as indicated for 24 hours. (B) Cells were pretreated with the indicated doses of fenretinide for 1 hour, and then treated with 1 μg/mL LPS for another 24 hours. (C) Cells were pretreated with GW9662 at the indicated doses for 30 minutes, and 10 μM fenretinide was then added to the culture medium for another 30 minutes. LPS (1 μg/mL) was further added to the cells for 24 hours. At the end of the experiments, the culture medium was collected for the determination of NO_x. The data are expressed as mean ± SEM and obtained from three individual experiments. *P<0.05; **P<0.01; ***P<0.001 as compared with the control group. ^#P<0.05; ^##P<0.01; ^###P<0.001 as compared with the LPS-treated group.
Abbreviations: FEN, fenretinide; LPS, lipopolysaccharide; NO, nitrogen oxide; PPARγ, peroxisome proliferator-activated receptor gamma; SEM, standard error of the mean; GW, GW9662.

Figure 5 Fenretinide controlled hypertension in SHR.

Notes: The WKY (white bars) and SHR (black bars) control groups were administered normal saline, the valsartan-treated SHR group was orally administered 15 mg/kg valsartan twice a day, and the fenretinide-treated SHR group was fed with standard diet supplemented with fenretinide at 737 μmol/kg diet for 1 week (n=8–10 for each group of the rats). Mean blood pressure (A) and systolic blood pressure (B) were measured with a noninvasive tail-cuff method in conscious animals using a computer-assisted detection device. (C) The expressions of PPARγ in the aorta of each group of the rats were tested by Western blots (n=4 for each group). *P<0.05; **P<0.01; ***P<0.001 as compared with the indicated groups.
Abbreviations: BP, blood pressure; FEN, fenretinide; PPARγ, peroxisome proliferator-activated receptor gamma; SHR, spontaneously hypertensive rats; WKY, Wistar-Kyoto rats.