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Efficacy of tomato concentrates in mouse models of dyslipidemia and cancer.

Chattopadhyay A, Grijalva V, Hough G, Su F, Mukherjee P, Farias-Eisner R, Anantharamaiah GM, Faull KF, Hwang LH, Navab M, Fogelman AM, Reddy ST - Pharmacol Res Perspect (2015)

Bottom Line: The same dose in a human would require three cups of tomato powder three times daily.To reduce the volume, we sought a method to concentrate 6F.Remarkably, extracting the transgenic freeze-dried tomato overnight in ethyl acetate with 5% acetic acid resulted in a 37-fold reduction in the amount of transgenic tomato needed for biologic activity.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.

ABSTRACT
We previously reported that adding freeze-dried tomato powder from transgenic plants expressing the apolipoprotein A-I mimetic peptide 6F at 2.2% by weight to a Western diet (WD) ameliorated dyslipidemia and atherosclerosis in mice. The same dose in a human would require three cups of tomato powder three times daily. To reduce the volume, we sought a method to concentrate 6F. Remarkably, extracting the transgenic freeze-dried tomato overnight in ethyl acetate with 5% acetic acid resulted in a 37-fold reduction in the amount of transgenic tomato needed for biologic activity. In a mouse model of dyslipidemia, adding 0.06% by weight of the tomato concentrate expressing the 6F peptide (Tg6F) to a WD significantly reduced plasma total cholesterol and triglycerides (P < 0.0065). In a mouse model of colon cancer metastatic to the lungs, adding 0.06% of Tg6F, but not a control tomato concentrate (EV), to standard mouse chow reduced tumor-associated neutrophils by 94 ± 1.1% (P = 0.0052), and reduced tumor burden by two-thirds (P = 0.0371). Adding 0.06% of either EV or Tg6F by weight to standard mouse chow significantly reduced tumor burden in a mouse model of ovarian cancer; however, Tg6F was significantly more effective (35% reduction for EV vs. 53% reduction for Tg6F; P = 0.0069). Providing the same dose of tomato concentrate to humans would require only two tablespoons three times daily making this a practical approach for testing oral apoA-I mimetic therapy in the treatment of dyslipidemia and cancer.

No MeSH data available.


Related in: MedlinePlus

Dose response of tomato concentrates in a mouse model of dyslipidemia. Female LDLR  mice 4–5 months of age (n = 8–24 mice per group) were fed a Western diet (WD) or WD supplemented with 0.015%, 0.03% or 0.06% tomato concentrate by weight or the mice were fed the freeze-dried transgenic tomatoes from which the concentrates were made added to the WD at 0.55%, 1.1% or 2.2% by weight as described in Materials and Methods. After 2 weeks the mice were fasted overnight and plasma total cholesterol and triglycerides were determined as described in Materials and Methods. (A and B) Plasma total cholesterol levels for mice receiving Tg6F or EV tomato concentrates, respectively. (C and D) Plasma triglyceride levels for mice receiving Tg6F or EV tomato concentrates, respectively. (E and F) Plasma total cholesterol levels for the mice in (A and B), respectively, compared to mice that received the freeze-dried transgenic tomatoes from which the concentrates were made. (G and H) Plasma triglyceride levels for the mice in (C and D), respectively, compared to mice that received the freeze-dried transgenic tomatoes from which the concentrates were made. The data shown are mean ± SEM. NS, not significant; Tg6F, tomato concentrate from transgenic tomatoes expressing the 6F peptide; EV, tomato concentrate from transgenic tomatoes expressing the marker protein, β-glucuronidase. The experiment was done once.
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fig02: Dose response of tomato concentrates in a mouse model of dyslipidemia. Female LDLR mice 4–5 months of age (n = 8–24 mice per group) were fed a Western diet (WD) or WD supplemented with 0.015%, 0.03% or 0.06% tomato concentrate by weight or the mice were fed the freeze-dried transgenic tomatoes from which the concentrates were made added to the WD at 0.55%, 1.1% or 2.2% by weight as described in Materials and Methods. After 2 weeks the mice were fasted overnight and plasma total cholesterol and triglycerides were determined as described in Materials and Methods. (A and B) Plasma total cholesterol levels for mice receiving Tg6F or EV tomato concentrates, respectively. (C and D) Plasma triglyceride levels for mice receiving Tg6F or EV tomato concentrates, respectively. (E and F) Plasma total cholesterol levels for the mice in (A and B), respectively, compared to mice that received the freeze-dried transgenic tomatoes from which the concentrates were made. (G and H) Plasma triglyceride levels for the mice in (C and D), respectively, compared to mice that received the freeze-dried transgenic tomatoes from which the concentrates were made. The data shown are mean ± SEM. NS, not significant; Tg6F, tomato concentrate from transgenic tomatoes expressing the 6F peptide; EV, tomato concentrate from transgenic tomatoes expressing the marker protein, β-glucuronidase. The experiment was done once.

Mentions: To determine the dose response of the tomato concentrates, we used a mouse model of dyslipidemia as shown in Figure2. The data in Figure2 demonstrate that the tomato concentrates were at least as effective in improving plasma lipids as was the starting material (i.e., the freeze-dried transgenic tomatoes from which the concentrates were made). Based on these results we used a dose of 0.06% by weight of the tomato concentrates in all subsequent experiments.


Efficacy of tomato concentrates in mouse models of dyslipidemia and cancer.

Chattopadhyay A, Grijalva V, Hough G, Su F, Mukherjee P, Farias-Eisner R, Anantharamaiah GM, Faull KF, Hwang LH, Navab M, Fogelman AM, Reddy ST - Pharmacol Res Perspect (2015)

Dose response of tomato concentrates in a mouse model of dyslipidemia. Female LDLR  mice 4–5 months of age (n = 8–24 mice per group) were fed a Western diet (WD) or WD supplemented with 0.015%, 0.03% or 0.06% tomato concentrate by weight or the mice were fed the freeze-dried transgenic tomatoes from which the concentrates were made added to the WD at 0.55%, 1.1% or 2.2% by weight as described in Materials and Methods. After 2 weeks the mice were fasted overnight and plasma total cholesterol and triglycerides were determined as described in Materials and Methods. (A and B) Plasma total cholesterol levels for mice receiving Tg6F or EV tomato concentrates, respectively. (C and D) Plasma triglyceride levels for mice receiving Tg6F or EV tomato concentrates, respectively. (E and F) Plasma total cholesterol levels for the mice in (A and B), respectively, compared to mice that received the freeze-dried transgenic tomatoes from which the concentrates were made. (G and H) Plasma triglyceride levels for the mice in (C and D), respectively, compared to mice that received the freeze-dried transgenic tomatoes from which the concentrates were made. The data shown are mean ± SEM. NS, not significant; Tg6F, tomato concentrate from transgenic tomatoes expressing the 6F peptide; EV, tomato concentrate from transgenic tomatoes expressing the marker protein, β-glucuronidase. The experiment was done once.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492730&req=5

fig02: Dose response of tomato concentrates in a mouse model of dyslipidemia. Female LDLR mice 4–5 months of age (n = 8–24 mice per group) were fed a Western diet (WD) or WD supplemented with 0.015%, 0.03% or 0.06% tomato concentrate by weight or the mice were fed the freeze-dried transgenic tomatoes from which the concentrates were made added to the WD at 0.55%, 1.1% or 2.2% by weight as described in Materials and Methods. After 2 weeks the mice were fasted overnight and plasma total cholesterol and triglycerides were determined as described in Materials and Methods. (A and B) Plasma total cholesterol levels for mice receiving Tg6F or EV tomato concentrates, respectively. (C and D) Plasma triglyceride levels for mice receiving Tg6F or EV tomato concentrates, respectively. (E and F) Plasma total cholesterol levels for the mice in (A and B), respectively, compared to mice that received the freeze-dried transgenic tomatoes from which the concentrates were made. (G and H) Plasma triglyceride levels for the mice in (C and D), respectively, compared to mice that received the freeze-dried transgenic tomatoes from which the concentrates were made. The data shown are mean ± SEM. NS, not significant; Tg6F, tomato concentrate from transgenic tomatoes expressing the 6F peptide; EV, tomato concentrate from transgenic tomatoes expressing the marker protein, β-glucuronidase. The experiment was done once.
Mentions: To determine the dose response of the tomato concentrates, we used a mouse model of dyslipidemia as shown in Figure2. The data in Figure2 demonstrate that the tomato concentrates were at least as effective in improving plasma lipids as was the starting material (i.e., the freeze-dried transgenic tomatoes from which the concentrates were made). Based on these results we used a dose of 0.06% by weight of the tomato concentrates in all subsequent experiments.

Bottom Line: The same dose in a human would require three cups of tomato powder three times daily.To reduce the volume, we sought a method to concentrate 6F.Remarkably, extracting the transgenic freeze-dried tomato overnight in ethyl acetate with 5% acetic acid resulted in a 37-fold reduction in the amount of transgenic tomato needed for biologic activity.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California, 90095-1736.

ABSTRACT
We previously reported that adding freeze-dried tomato powder from transgenic plants expressing the apolipoprotein A-I mimetic peptide 6F at 2.2% by weight to a Western diet (WD) ameliorated dyslipidemia and atherosclerosis in mice. The same dose in a human would require three cups of tomato powder three times daily. To reduce the volume, we sought a method to concentrate 6F. Remarkably, extracting the transgenic freeze-dried tomato overnight in ethyl acetate with 5% acetic acid resulted in a 37-fold reduction in the amount of transgenic tomato needed for biologic activity. In a mouse model of dyslipidemia, adding 0.06% by weight of the tomato concentrate expressing the 6F peptide (Tg6F) to a WD significantly reduced plasma total cholesterol and triglycerides (P < 0.0065). In a mouse model of colon cancer metastatic to the lungs, adding 0.06% of Tg6F, but not a control tomato concentrate (EV), to standard mouse chow reduced tumor-associated neutrophils by 94 ± 1.1% (P = 0.0052), and reduced tumor burden by two-thirds (P = 0.0371). Adding 0.06% of either EV or Tg6F by weight to standard mouse chow significantly reduced tumor burden in a mouse model of ovarian cancer; however, Tg6F was significantly more effective (35% reduction for EV vs. 53% reduction for Tg6F; P = 0.0069). Providing the same dose of tomato concentrate to humans would require only two tablespoons three times daily making this a practical approach for testing oral apoA-I mimetic therapy in the treatment of dyslipidemia and cancer.

No MeSH data available.


Related in: MedlinePlus