Prevention of malathion-induced depletion of cardiac cells mitochondrial energy and free radical damage by a magnetic magnesium-carrying nanoparticle

Abstract

The present work was designed to examine the effect of a new (25)Mg(2+)-carrying nanoparticle (PMC16) on energy and oxidative stress parameters inside the heart of the rats exposed to acute mild toxic dose of malathion, a widely used organophosphate. Post a single intraperitoneal (ip) injection of malathion (0.25 of LD50), PMC16 at different doses (0.05, 0.1, and 0.2 of LD50) was administered intravenously (iv) as a supplement to standard therapy of atropine and pralidoxime. MgSO(4) was used as another supplement for comparison with PMC16. Oxidative stress biomarkers including lipid peroxidation (LPO) and reactive oxygen species (ROS), antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), ATP/ADP ratio, and Mg in the cardiac cells were determined. Results indicated a significant increase in LPO, ROS, ADP/ATP ratio, and a decrease in Mg post-malathion poisoning in comparison to controls. All of these parameters were improved by use of standard therapy either with MgSO4 or various doses of PMC16. The activities of SOD, CAT, and GPx did not change significantly in the present acute malathion poisoning model and neither MgSO(4) or PMC16 had no considerable improvement on these parameters. Comparing groups that received normal Mg and those of various doses of PMC16, a significant difference was found with the PMC16 (0.2 LD50) group. PMC16 0.2 reduced cardiac cells LPO and ROS of Mal-exposed animals rather than that of MgSO4. PMC16 0.2 was also significantly better than MgSO(4) in improving MAL-induced changes in ADP/ATP ratio and also intracellular Mg levels. This study illustrates that malathion-induced cardiac cells toxicity is improved by administration of Mg as a result of increasing cardiac ATP through active transport of Mg inside the cells. Finally, the results of this study support positive effects of this magnetic Mg nanoparticle carrier but do not confirm its absolute efficacy that remains to be explored by further tests in different animal models and organs before moving to a phase I human trial.

Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research

“…Since, there are limited data about the hepatotoxicity of OPs in humans, it is not certain whether changes in biochemical parameters indicate actual liver damage. (90)(91)(92)(93)(94), energy production (93,(95)(96)(97), and cell death (98)(99)(100). Several studies have found an association between mitochondrial dynamics and malathion-induced drop in mitochondrial ATP synthesis in rat liver (9) or quinalphos and acephate effects on liver succinic dehydrogenase (84,85,101) and ATPase activities (87) -all of them the key enzymes for oxidative phosphorylation.…”

Blockage of both the extrinsic and intrinsic pathways of diazinon-induced apoptosis in PaTu cells by magnesium oxide and selenium nanoparticles

“…12,13 Previous studies have examined the protective effects of MgO NPs on oxidative stress parameters induced by malathion and chlorpyrifos, the widely used OP. 13,14 It was observed that malathion-induced cardiac cell toxicity is improved by administration of Mg as a result of increasing cardiac adenosine triphosphate (ATP) through active transport of Mg inside the cells. Due to the increasing level of ATP through the liberation of MgO into cells and the improvement of hypoxia, MgO NPs can protect mitochondria against the temporary cardiac arrest.…”

“…Due to the increasing level of ATP through the liberation of MgO into cells and the improvement of hypoxia, MgO NPs can protect mitochondria against the temporary cardiac arrest. 14 In chlorpyrifos-induced lymphocytes, treatment with MgO NPs could ameliorate the toxic effects of OP pesticide by increasing the viability and decreasing apoptosis, oxidative stress, and inflammation. 13 Moreover, previous in vitro and in vivo studies have elucidated the protective role of selenium NP (Se NP).…”

Neurocognitive, Mental Health, and Glucose Disorders in Farmers Exposed to Organophosphorus Pesticides

“…These compounds can affect mammalian systems by inhibiting acetylcholinesterase (AChE) at the synapses and muscular junctions, which may result in hypercholinergic preponderance. Apparently, the mechanisms causing brain, muscle or other organ damage by OPs are mostly related to a change in oxidant-antioxidant balance, which in turn results in free radical-mediated injury, as supported by many studies (3)(4)(5)(6)(7)(8)(9)(10). Careless use of pesticides like OPs may cause diverse health complications by upsetting the nervous, endocrine, reproductive, and immune systems (11)(12)(13).…”