Oxidative damage to rat brain in iron and copper overloads

Abstract

This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 μg of Fe per g and from 3.6 to 34 μg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 μg of Fe per g of brain and 15 μg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 μg of Fe per g and 20 μg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 μg of Fe per g and 18% for Cu with a C50 of 10 μg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.

Prophylactic Administration of Nanocurcumin Abates the Incidence of Liver Toxicity Induced by an Overdose of Copper Sulfate: Role of CYP4502E1, NF-κB and Bax Expressions

“…6 Therefore, the protective effects of CM may be related to their ability to chelate/sequester Cu via formation of complexes. 4,31…”

“…6 Therefore, the protective effects of CM may be related to their ability to chelate/sequester Cu via formation of complexes. 4,31 Persichini et al 8 reported that hyper-cupremic situations may lead to the onset of inflammation through production of ROS and activation of NF-kB-dependent gene which involved in the inflammatory response and hence production of TNF-a and induction of NOS-II and COX. 2 Herein, hepatic NO and gene expression of NF-kB were upregulated by toxic dose of CuSO 4 , while treatments with the antioxidants in question declined the previous parameters.…”

“…3 CuSO 4 produces toxic effects in the liver and brain due to its production of the highly reactive HO• species. 4 Cu stimulates oxidative stress by triggering of reactive oxygen species (ROS) and declines of the activities of some free-radical scavenging enzymes including catalase (CAT) and superoxide dismutase (SOD), and the level of reduced glutathione (GSH). 5 The inhibitory effect of copper on CAT, SOD, and GSH may be due to oxidative alteration of the enzymatic proteins and biomembrane lipids by ROS.…”

Iron and Copper Toxicity in Rat Liver: A Kinetic and Holistic Overview

“…In Fe overload, 90% of the rats survived the observation time of 48 h, whereas in Cu overload, 85% of the animals survived 24 h and 60% survived 48 h. 3 Metal accumulation in the liver was dose-and time-dependent. 1 The liver content of Fe increased 1.6 times and the one of Cu 11-fold after 48 h of metal overloads.…”

“…Both metals are clearly hormetic, they are required at low levels for human health (Recommended Daily Intake: 10-15 mg Fe/ day and 1-3 mg Cu/day) but at higher levels (more than 30 mg Fe/day or 8 mg Cu/day) they produce toxic effects in liver and brain. [1][2][3][4] The metal toxicity seems due to their participation in the Haber-Weiss redox reaction that produces the highly reactive HO…”