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Combination of Nigella sativa with Glycyrrhiza glabra and Zingiber officinale augments their protective effects on doxorubicin-induced toxicity in h9c2 cells.

Hosseini A, Shafiee-Nick R, Mousavi SH - Iran J Basic Med Sci (2014)

Bottom Line: Co-treatment of the cells with each herb extract increased viability of cells dose-dependently with a maximum protection effect of about 30%, and their potencies were N>G>Z.The combination of the threshold dose of each extract (NGZ) produced a similar effect, which was increased dose-dependently to a maximum protection of 70%.These effects were correlated with the effects of NGZ on ROS and MDA.

View Article: PubMed Central - PubMed

Affiliation: Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

ABSTRACT

Objectives: The use of doxorubicin (DOX) is limited by its dose-dependent cardio toxicity in which reactive Oxygen Species (ROS) play an important role in the pathological process. The aim of this study was to evaluate the protective effect of three medicinal plants, Nigella sativa (N), Glycyrrhiza glabra (G) and Zingiber officinale (Z), and their combination (NGZ), against DOX-induced apoptosis and death in H9c2 cells.

Materials and methods: The cells were incubated with different concentrations of each extract or NGZ for 4 hr which continued in the presence or absence of 5µM doxorubicin for 24 hr. Cell viability and the apoptotic rate were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) and propidium iodide (PI) staining assays, respectively. The level of ROS and lipid peroxidation were measured by fluorimetric methods.

Results: Treatment with doxorubicin increased ROS generation, enhanced malondialdehyde (MDA) formation, and induced apoptosis. Co-treatment of the cells with each herb extract increased viability of cells dose-dependently with a maximum protection effect of about 30%, and their potencies were N>G>Z. The combination of the threshold dose of each extract (NGZ) produced a similar effect, which was increased dose-dependently to a maximum protection of 70%. These effects were correlated with the effects of NGZ on ROS and MDA.

Conclusion: All of the extracts have some protective effects against DOX-induced toxicity in cardiomyocytes with similar efficacies, but with different potencies. However, NGZ produced much higher protective effect via reducing oxidative stress and inhibiting of apoptotic induction processes. Further investigations are needed to determine the effects of NGZ on DOX chemotherapy.

No MeSH data available.


Related in: MedlinePlus

Effect of NGZ on DOX-induced MDA production (Figure 2A) and reactive oxygen species (ROS) generation (Figure 2B) in H9c2 cells. Cells were pretreated with different concentrations of NGZ for 4 hr before exposure to 5 µM of DOX for 24 hr. Data are expressed as mean ± SEM of three separate experiments ###P<0.001 versus control, *P<0.05, **P<0.01 and ***P<0.001 versus DOX
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Figure 2: Effect of NGZ on DOX-induced MDA production (Figure 2A) and reactive oxygen species (ROS) generation (Figure 2B) in H9c2 cells. Cells were pretreated with different concentrations of NGZ for 4 hr before exposure to 5 µM of DOX for 24 hr. Data are expressed as mean ± SEM of three separate experiments ###P<0.001 versus control, *P<0.05, **P<0.01 and ***P<0.001 versus DOX

Mentions: The biochemical determination of malondialdehyde (MDA) represents lipid peroxide formation. The results showed that DOX significantly increased MDA (P<0.001) and ROS (P<0.001) levels in H9c2 compared with control cells. In the presence of DOX, treatment with 125 µg/ml (P<0.05), 250 µg/ml (P<0.001) and 500 µg/ml (P<0.01) doses of NGZ significantly reduced the level of MDA. The most reduction of MDA was observed at the dose of 250 µg/ml (control 100±1.4, DOX 235±7.9 and 250 µg/ml NGZ 119±5.18). Also this combination diminished significantly ROS production in comparison with DOX, at dose of 125 µg/ml (P<0.01), 250 µg/ml (P<0.001) and 500 µg/ml (P<0.01) (Figures 2A and 2B, respectively). The lowest production of ROS was at the dose of 250 µg/ml (control 27±4, DOX 120±8 and 250 µg/ml NGZ 45±4).


Combination of Nigella sativa with Glycyrrhiza glabra and Zingiber officinale augments their protective effects on doxorubicin-induced toxicity in h9c2 cells.

Hosseini A, Shafiee-Nick R, Mousavi SH - Iran J Basic Med Sci (2014)

Effect of NGZ on DOX-induced MDA production (Figure 2A) and reactive oxygen species (ROS) generation (Figure 2B) in H9c2 cells. Cells were pretreated with different concentrations of NGZ for 4 hr before exposure to 5 µM of DOX for 24 hr. Data are expressed as mean ± SEM of three separate experiments ###P<0.001 versus control, *P<0.05, **P<0.01 and ***P<0.001 versus DOX
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4387235&req=5

Figure 2: Effect of NGZ on DOX-induced MDA production (Figure 2A) and reactive oxygen species (ROS) generation (Figure 2B) in H9c2 cells. Cells were pretreated with different concentrations of NGZ for 4 hr before exposure to 5 µM of DOX for 24 hr. Data are expressed as mean ± SEM of three separate experiments ###P<0.001 versus control, *P<0.05, **P<0.01 and ***P<0.001 versus DOX
Mentions: The biochemical determination of malondialdehyde (MDA) represents lipid peroxide formation. The results showed that DOX significantly increased MDA (P<0.001) and ROS (P<0.001) levels in H9c2 compared with control cells. In the presence of DOX, treatment with 125 µg/ml (P<0.05), 250 µg/ml (P<0.001) and 500 µg/ml (P<0.01) doses of NGZ significantly reduced the level of MDA. The most reduction of MDA was observed at the dose of 250 µg/ml (control 100±1.4, DOX 235±7.9 and 250 µg/ml NGZ 119±5.18). Also this combination diminished significantly ROS production in comparison with DOX, at dose of 125 µg/ml (P<0.01), 250 µg/ml (P<0.001) and 500 µg/ml (P<0.01) (Figures 2A and 2B, respectively). The lowest production of ROS was at the dose of 250 µg/ml (control 27±4, DOX 120±8 and 250 µg/ml NGZ 45±4).

Bottom Line: Co-treatment of the cells with each herb extract increased viability of cells dose-dependently with a maximum protection effect of about 30%, and their potencies were N>G>Z.The combination of the threshold dose of each extract (NGZ) produced a similar effect, which was increased dose-dependently to a maximum protection of 70%.These effects were correlated with the effects of NGZ on ROS and MDA.

View Article: PubMed Central - PubMed

Affiliation: Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

ABSTRACT

Objectives: The use of doxorubicin (DOX) is limited by its dose-dependent cardio toxicity in which reactive Oxygen Species (ROS) play an important role in the pathological process. The aim of this study was to evaluate the protective effect of three medicinal plants, Nigella sativa (N), Glycyrrhiza glabra (G) and Zingiber officinale (Z), and their combination (NGZ), against DOX-induced apoptosis and death in H9c2 cells.

Materials and methods: The cells were incubated with different concentrations of each extract or NGZ for 4 hr which continued in the presence or absence of 5µM doxorubicin for 24 hr. Cell viability and the apoptotic rate were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) and propidium iodide (PI) staining assays, respectively. The level of ROS and lipid peroxidation were measured by fluorimetric methods.

Results: Treatment with doxorubicin increased ROS generation, enhanced malondialdehyde (MDA) formation, and induced apoptosis. Co-treatment of the cells with each herb extract increased viability of cells dose-dependently with a maximum protection effect of about 30%, and their potencies were N>G>Z. The combination of the threshold dose of each extract (NGZ) produced a similar effect, which was increased dose-dependently to a maximum protection of 70%. These effects were correlated with the effects of NGZ on ROS and MDA.

Conclusion: All of the extracts have some protective effects against DOX-induced toxicity in cardiomyocytes with similar efficacies, but with different potencies. However, NGZ produced much higher protective effect via reducing oxidative stress and inhibiting of apoptotic induction processes. Further investigations are needed to determine the effects of NGZ on DOX chemotherapy.

No MeSH data available.


Related in: MedlinePlus