Epigallocatechin-3-gallate protects rat brain mitochondria against cadmium-induced damage.

Many health claims have been made about the medicinal benefits of drinking green tea, including neuroprotection. This study mainly focuses on Epigallocatechin 3-gallate (EGCG), a potent antioxidant, which is abundantly found in green tea. Cadmium [Cd(2+)] is a toxic pollutant that leads to neurotoxicity in both animals and humans. Although the entrance of Cd(2+) in the adult central nervous system is limited, developmental neurotoxicity has been evidenced as result of the blood-brain barrier (BBB) immaturity. Moreover, high Cd(2+) levels are known to impair BBB function. Furthermore, the molecular mechanisms related to its neurotoxic properties remain unknown. This study evaluates the potential protective effect of the major green tea polyphenol, EGCG, against Cd(2+)-induced mitotoxicity under in vitro conditions, using mitochondrial-enriched fractions from rat brain. Co-incubation of EGCG with Cd(2+) prevented the Cd(2+)-induced mitochondrial dysfunction (capacity to reduce MTT to formazan). In addition, EGCG completely prevented mitochondrial lipid peroxidation induced by Cd(2+) but did not affect non protein thiols levels. Spectroscopic studies have shown EGCG able to form a chemical complex with Cd(2+), in an equimolar ratio. In this study we demonstrate EGCG effectiveness in protecting against Cd(2+)-induced mitochondrial dysfunction and lipid peroxidation probably due to its antioxidant and chelating effects.

Effects of K074 and pralidoxime on antioxidant and acetylcholinesterase response in malathion-poisoned mice.

The organophosphorus (OP) pesticide malathion is a highly neurotoxic compound and its toxicity is primarily caused by the inhibition of acetylcholinesterase (AChE), leading to cholinergic syndrome. Although oximes have been used as potential antidotal treatments in malathion poisoning because of their potential capability to reactivate the inhibited enzyme, the clinical experience with the clinically available oximes (e.g. pralidoxime) is disappointing and their routine use has been questioned. In the present study, we investigated the potency of pralidoxime and K074 in reactivating AChE after acute exposure to malathion, as well as in preventing malathion-induced changes in oxidative-stress related parameters in mice. Malathion (1.25 g/kg, s.c.) induced a significant decrease in cortico-cerebral, hippocampal and blood AChE activities at 24h after exposure. Oxime treatments (1/4 of LD(50), i.m., 6h after malathion poisoning) showed that pralidoxime significantly reversed malathion-induced blood AChE inhibition, although no significant effects were observed after K074 treatment. Interestingly, both oximes tested were unable to reactivate the cortico-cerebral and hippocampal enzymes after intramuscular or intracerebroventricular injection (1/4 of LD(50), 6h after malathion poisoning). Biochemical parameters related to oxidative stress (cerebro-cortical and hippocampal glutathione peroxidase, glutathione reductase and catalase activities, as well as lipid peroxidation) were not affected in animals treated with malathion, oximes or atropine alone. However, pralidoxime and K074, administered intramuscularly 6h after malathion poisoning, were able to increase the endogenous activities of these antioxidant enzymes in the prefrontal cortex and hippocampus. Taken together, the results presented herein showed that pralidoxime (the most common clinically used oxime) and the recently developed oxime K074, administered 6h after malathion poisoning, were unable to reactivate the inhibited AChE in mouse prefrontal cortex and hippocampus. However, only pralidoxime significantly reversed the blood AChE inhibition induced by malathion poisoning. This indicates that peripheral and central AChE activities are not necessarily correlated after the treatment of OP compounds and/or oximes, which should be taken into account in the diagnosis and management of OP-exposed humans. In addition, considering that the available treatments to malathion poisoning appear to be ineffective, the present study reinforce the need to search for potential new AChE reactivators able to efficiently reactivate the brain and blood AChEs after malathion poisoning.