Effects of Acute Manganese Chloride Exposure on Lipid Peroxidation and Alteration of Trace Metals in Rat Brain

Abstract

Although manganese (Mn) is an essential element, exposure to excessive levels of Mn and its accumulation in the brain can cause neurotoxicity and extrapyramidal syndrome. We have investigated the differences in the accumulated levels of Mn, the degree of lipid peroxidation, and its effects on the levels of trace elements (Fe, Cu, and Zn) in various regions in the brain of rats having undergone acute Mn exposure. The rats in the dose-effect group were injected intraperitoneally (ip) with MnCl2 (25, 50, or 100 mg MnCl2/kg ) once a day for 24 h. The Mn significantly accumulated (p<0.05) in the frontal cortex, corpus callosum, hippocampus, striatum, hypothalamus, medulla, cerebellum, and spinal cord in each case. The rats in the time-course group were ip injected with MnCl2 (50 mg MnCl2/kg) and then monitored 12, 24, 48, and 72 h after exposure. The Mn accumulated in the frontal cortex, corpus callosum, hippocampus, striatum hypothalamus, medulla, cerebellum, and spinal cord after these periods of time, In both the dose-effect and time-course studies, we observed that the concentration of malondialdehyde, an end product of lipid peroxidation, increased significantly in the frontal cortex, hippocampus, striatum, hypothalamus, medulla, and cerebellum. However, no relationship between the concentrations of Mn in the brain and the extent of lipid peroxidation was observed. In addition, we found that there was a significant increase (p<0.05) in the level of Fe in the hippocampus, striatum, hypothalamus, medulla, and cerebellum, but the Cu and Zn levels had not changed significantly. These findings indicated that Mn induces an increase in the iron level, which provides direct evidence for Fe-mediated lipid peroxidation in the rats' brains; these phenomena might play important roles in the mechanisms of Mn-induced neurotoxicology.

Effects of Acute Manganese Neurotoxicity in Young Chicks

“…Manganese accumulates in brain regions rich in dopamine (40). In support of this claim, Mn levels increased in the entire brain 1.25 to 4 times following i.m.…”

Effects of Short‐Term Exposure to Manganese on the Adult Rat Brain Antioxidant Status and the Activities of Acetylcholinesterase, (Na+,K+)‐ATPase and Mg2+‐ATPase: Modulation by l‐Cysteine

“…Because Cys did not cause a significant increase in the rat brain TAS by itself, the partially corrected Mn-induced TAS decrease by Mn + Cys co-administration could be due to the chelating properties of Cys (assisting to the biological inactivation and/or excretion of Mn ions). It should be noted that Mn brain concentrations have not been related to the extent of lipid peroxidation [32] or to the oxidative stress biomarkers' alterations [31] observed in certain animal brain regions after exposure to Mn, and that such alterations might be (in some extent) reversible [33]. However, Cys (at least under the examined experimental conditions) was not proved sufficiently efficient to neutralize the Mn-induced oxidative stress.…”

Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal

“…Redox active transition metals have ability to induce and initiate lipid peroxidation through the production of oxygen radicals, mainly hydroxyl radical, via Fenton's/Haber-Weiss reactions [63, 406]. Transition metal, including copper [407–410], chromium [411, 412], cadmium [413–416], nickel [417, 418], vanadium [419–421], manganese [59, 422–424], and iron [59, 407, 425–434] has been utilized to induce lipid peroxidation in vivo mammalian model.…”