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

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.

Keywords: MiADMSA; arsenic; chelation; gallic acid; oxidative stress.

Figure 1

Structure of Gallic acid.

Figure 2

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.

Figure 3

Effect of MiADMSA alone or in combination with gallic acid on brain ROS, GSH, and TBARS 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 (in fluorescence intensity units); GSH, reduced glutathione (mg/mL); TBARS, thiobarbituric reactive substances expressed (nmoles of TBARS/gm of tissue).

Figure 4

Effect of MiADMSA alone or in combination with gallic acid on liver ROS, GSH, and TBARS 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 (in fluorescence intensity units); GSH, reduced glutathione levels (in mg/g tissue weight); TBARS, thiobarbituric reactive substances (in nmoles of TBARS/g of tissue).

Figure 5

Effect of MiADMSA alone or in combination with gallic acid on urinary levels of 8-OHdG 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: 8-OHdG, 8-oxo-7,8-dihydro-2 deoxyguanosine (ng/dl urinary volume).