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Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse.

Pachauri V, Flora S - Biochem Insights (2015)

Bottom Line: The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic.Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA.We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

View Article: PubMed Central - PubMed

Affiliation: Division of Regulatory Toxicology, Defence Research and Development Establishment, Gwalior, India.

ABSTRACT
Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

No MeSH data available.


Related in: MedlinePlus

Effect of MiADMSA alone or in combination with gallic acid on blood ROS, GSH, and ALAD levels in arsenic-exposed mice. Groups: 1, control (no treatment); 2, MiADMSA; 3, gallic acid; 4, arsenic; 5, arsenic + MiADMSA; 6, arsenic + gallic acid; 7, arsenic + gallic acid + MiADMSA.Notes: Values are mean ± SE; n = 8. *,†,‡Values with matching symbol notations in each graph are not statistically significant at 5% level of probability.Abbreviations and units: ROS, reactive oxygen species as fluorescence intensity unit; GSH, reduced glutathione as mg/mL; ALAD, δ-aminolevulinic acid dehydratase as nmol/min/ml erythrocytes.
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f2-bci-8-2015-001: Effect of MiADMSA alone or in combination with gallic acid on blood ROS, GSH, and ALAD levels in arsenic-exposed mice. Groups: 1, control (no treatment); 2, MiADMSA; 3, gallic acid; 4, arsenic; 5, arsenic + MiADMSA; 6, arsenic + gallic acid; 7, arsenic + gallic acid + MiADMSA.Notes: Values are mean ± SE; n = 8. *,†,‡Values with matching symbol notations in each graph are not statistically significant at 5% level of probability.Abbreviations and units: ROS, reactive oxygen species as fluorescence intensity unit; GSH, reduced glutathione as mg/mL; ALAD, δ-aminolevulinic acid dehydratase as nmol/min/ml erythrocytes.

Mentions: Arsenic exposure resulted in changes in the biochemical endpoints in blood, suggesting oxidative stress (Fig. 2). ROS and GSH levels increased, while ALAD activity showed significant depletion on arsenic exposure. Oxidative stress reflects a disturbance in the balance between the systemic production of ROS and antioxidant defenses against these free radicals. The assessment of GSH levels is a useful indication of the redox potential and the cell’s ability to prevent oxidative stress. Inhibition of ALAD enzyme by arsenic leads to decreased heme synthesis and ultimately anemia. ALAD inactivation may also lead to the accumulation of ALA, which can cause an overproduction of ROS, which in part could explain arsenic-induced oxidative stress. While the combined administration of MiADMSA and gallic acid led to an increased ROS level, GSH too showed an increase. Administration of MiADMSA, gallic acid, and their combination proved effective in increasing ALAD activity toward normal level.


Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse.

Pachauri V, Flora S - Biochem Insights (2015)

Effect of MiADMSA alone or in combination with gallic acid on blood ROS, GSH, and ALAD levels in arsenic-exposed mice. Groups: 1, control (no treatment); 2, MiADMSA; 3, gallic acid; 4, arsenic; 5, arsenic + MiADMSA; 6, arsenic + gallic acid; 7, arsenic + gallic acid + MiADMSA.Notes: Values are mean ± SE; n = 8. *,†,‡Values with matching symbol notations in each graph are not statistically significant at 5% level of probability.Abbreviations and units: ROS, reactive oxygen species as fluorescence intensity unit; GSH, reduced glutathione as mg/mL; ALAD, δ-aminolevulinic acid dehydratase as nmol/min/ml erythrocytes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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f2-bci-8-2015-001: Effect of MiADMSA alone or in combination with gallic acid on blood ROS, GSH, and ALAD levels in arsenic-exposed mice. Groups: 1, control (no treatment); 2, MiADMSA; 3, gallic acid; 4, arsenic; 5, arsenic + MiADMSA; 6, arsenic + gallic acid; 7, arsenic + gallic acid + MiADMSA.Notes: Values are mean ± SE; n = 8. *,†,‡Values with matching symbol notations in each graph are not statistically significant at 5% level of probability.Abbreviations and units: ROS, reactive oxygen species as fluorescence intensity unit; GSH, reduced glutathione as mg/mL; ALAD, δ-aminolevulinic acid dehydratase as nmol/min/ml erythrocytes.
Mentions: Arsenic exposure resulted in changes in the biochemical endpoints in blood, suggesting oxidative stress (Fig. 2). ROS and GSH levels increased, while ALAD activity showed significant depletion on arsenic exposure. Oxidative stress reflects a disturbance in the balance between the systemic production of ROS and antioxidant defenses against these free radicals. The assessment of GSH levels is a useful indication of the redox potential and the cell’s ability to prevent oxidative stress. Inhibition of ALAD enzyme by arsenic leads to decreased heme synthesis and ultimately anemia. ALAD inactivation may also lead to the accumulation of ALA, which can cause an overproduction of ROS, which in part could explain arsenic-induced oxidative stress. While the combined administration of MiADMSA and gallic acid led to an increased ROS level, GSH too showed an increase. Administration of MiADMSA, gallic acid, and their combination proved effective in increasing ALAD activity toward normal level.

Bottom Line: The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic.Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA.We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

View Article: PubMed Central - PubMed

Affiliation: Division of Regulatory Toxicology, Defence Research and Development Establishment, Gwalior, India.

ABSTRACT
Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

No MeSH data available.


Related in: MedlinePlus