Monensin potentiates lead chelation efficacy of MiADMSA in rat brain post chronic lead exposure

The present study evaluates combination therapy with a chelating agent, MiADMSA and a Na+ ionophore, monensin against sub-chronic lead toxicity in rats. Animals were exposed to 0.1% lead in drinking water for 16 weeks and then treated with either MiADMSA at 50 mg/kg body weight, or monensin at 10 mg/kg, or both in combination for a period of 5 days was administered. Biomarkers indicative of oxidative stress like ROS, GSH, GSSG and TBARS demonstrated lead-induced toxic manifestations in blood, kidney and brain. Antioxidants like SOD, catalase and glutathione peroxidase along with specific lead biomarker, blood ALAD were also severely depleted in lead intoxicated animals. Serum parameters and histopathological findings supported the said results. MiADMSA treatment during both mono- and combination therapy with monensin, restored the antioxidant status and recovered biochemical and haematological variables due to lead. However, monensin alone was not found to be effective in the given scenario. Interestingly, combination therapy in its ability to revert lead-induced overall systemic toxicity was only found at par with the MiADMSA monotherapy except for its chelation potential. Monensin given in combination with MiADMSA potentiated its lead chelation ability especially from brain, along with maintaining the normal copper concentrations in the organ unlike MiADMSA monotherapy.