Background
Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated, at least in part, by oxidative stress.
Objectives
The present study was undertaken to test the hypothesis that a decrease in acetylcholinesterase (AChE) activity mediates Mn-induced neurotoxicity.
Methods
Groups of 6 rats received 4 or 8 intraperitoneal (i.p.) injections of 25 mg MnCl2/kg/day, every 48 hours. Twenty-four hours after the last injection, brain AChE activity and the levels of F2-isoprostanes (F2-IsoPs) and F4-neuroprostanes (F4-NPs) (biomarkers of oxidative stress), as well as prostaglandin E2 (PGE2) (biomarker of neuroinflammation) were analyzed.
Results
The results showed that after either 4 or 8 Mn doses, brain AChE activity was significantly decreased (p<0.05), to 60 ± 16 % and 55 ± 13 % of control levels, respectively. Both treated groups exhibited clear signs of neurobehavioral toxicity, characterized by a significant (p<0.001) decrease in ambulation and rearings in open-field. Furthermore, Mn treatment caused a significant increase (p<0.05) in brain F2-IsoPs and PGE2 levels, but only after 8 doses. In rats treated with 4 Mn doses, a significant increase (p<0.05) in brain F4-NPs levels was found. To evaluate cellular responses to oxidative stress, we assessed brain nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and Mn-superoxide dismutase (Mn-SOD, SOD2) protein expression levels. A significant increase in Mn-SOD protein expression (p<0.05) and a trend towards increased Nrf2 protein expression was noted in rat brains after 4 Mn doses vs. the control group, but the expression of these proteins was decreased after 8 Mn doses. Taken together, these results suggest that the inhibitory effect of Mn on AChE activity promotes increased neuronal oxidative stress and neuroinflammatory biomarkers.
The iatrogenic risks associated with excessive Mn administration in parenteral nutrition (PN) patients are well documented. Hypermanganesemia and neurotoxicity are associated with the duration of Mn supplementation, Mn dosage, as well as pathological conditions, such as anemia or cholestasis. Recent PN guidelines recommend the biomonitoring of patients if they receive Mn in their PN longer than 30 days. The data in the literature are conflicting about the method for assessing Mn stores in humans as a definitive biomarker of Mn exposure or induced-neurotoxicity has yet to be identified. The biomonitoring of Mn relies on the analysis of whole blood Mn (WB Mn) levels, which are highly variable among human population and are not strictly correlated with Mn-induced neurotoxicity. Alterations in dopaminergic (DAergic) and catecholaminergic metabolism have been studied as predictive biomarkers of Mn-induced neurotoxicity. Given these limitations, this review addresses various approaches for biomonitoring Mn exposure and neurotoxic risk.
a b s t r a c tSubmergence is one of the major constrains affecting wetland plants, with inevitable impacts on their physiology and productivity. Global warming as a driving force of sea level rise, tend to increase the submersion periods duration. Photosynthesis biophysical probing arise as an important tool to understand the energetics underlying plant feedback to these constrains. As in previous studies with Spartina maritima, there was no inhibition of photosynthetic activity in submerged individuals. Comparing both donor and acceptor sides of the PSII, the first was more severely affected during submersion, driven by the inactivation of the OEC with consequent impairment of the ETC. Although this apparent damage in the PSII donor side, the electron transport per active reaction centre was not substantially affected, indicating that this reduction in the electron flow is accompanied by a proportional increase in the number of active reaction centres. These conditions lead to the accumulation of excessive reducing power, source of damaging ROS, counteracted by efficient energy dissipation processes and anti-oxidant enzymatic defences. This way, S. maritima appears as a well-adapted species with an evident photochemical plasticity towards submersion, allowing it to maintain its photosynthetic activity even during prolonged submersion periods.
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