title: Short-term exposure to nickel alters the adult rat brain antioxidant status and the activities of crucial membrane-bound enzymes: neuroprotection by L-cysteine.
abstract: Nickel (Ni) is an environmental pollutant towards which human exposure can be both occupational (mainly through inhalation) and dietary (through water and food chain-induced bioaccumulation). The aim of this study was to investigate the effects of short-term Ni-administration (as NiCl(2), 13 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase, and Mg(2+)-ATPase; in addition, the potential effect of the co-administration of the antioxidant L-cysteine (Cys, 7 mg/kg) on the above parameters was studied. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Ni), C (Cys), and D (Ni and Cys). All rats were treated once daily with intraperitoneal injections of the tested compounds, for 1-week. Rats were sacrificed by decapitation and the above-mentioned parameters were measured spectrophotometrically. Rats treated with Ni exhibited a significant reduction in brain TAS (-47%, p < 0.001, BvsA) that was efficiently limited by the co-administration of Cys (-4%, p > 0.05, DvsA; +83%, p < 0.001, DvsB), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both Ni (+30%, p < 0.001, BvsA) and Cys (+62%, p < 0.001, CvsA), while it tended to adjust to control levels by the co-administration of Ni and Cys (+13%, p < 0.001, DvsA; -13%, p < 0.001, DvsB). The activity of rat brain Na(+),K(+)-ATPase was significantly decreased by Ni-administration (-49%, p < 0.001, BvsA), while Cys supplementation could not reverse this decrease (-44%, p < 0.001, DvsA). The activity of Mg(2+)-ATPase was not affected by Ni-administration (-3%, p > 0.05, BvsA), but was significantly reduced when combined with Cys administration (-17%, p < 0.001, DvsA). The above findings suggest that Ni short-term in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed to control levels by Cys co-administration; Cys could thus be considered (for future applications) as a potential neuroprotective agent against chronic exposure to Ni. The activity of Na(+),K(+)-ATPase that was inhibited by Ni, could not be reversed by Cys co-administration. The matter requires further investigation in order to fully elucidate the spectrum of the neurotoxic effects of Ni.
authors.affiliation: Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Charis
authors.initials: C
authors.lastname: Liapi
authors.forename: Apostolos
authors.initials: A
authors.lastname: Zarros
authors.forename: Stamatios
authors.initials: S
authors.lastname: Theocharis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Voumvourakis
authors.forename: Foteini
authors.initials: F
authors.lastname: Anifantaki
authors.forename: Elena
authors.initials: E
authors.lastname: Gkrouzman
authors.forename: Zois
authors.initials: Z
authors.lastname: Mellios
authors.forename: Nikolina
authors.initials: N
authors.lastname: Skandali
authors.forename: Hussam
authors.initials: H
authors.lastname: Al-Humadi
authors.forename: Stylianos
authors.initials: S
authors.lastname: Tsakiris
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009532:Nickel / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D009532:Nickel; D000110:Acetylcholinesterase; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D003545:Cysteine