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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.

Uncontrolled diabetes is known to affect the nervous system. The aim of this study was to investigate the effect of the antioxidant L: -cysteine (Cys) on the changes caused by adult-onset streptozotocin (STZ)-induced diabetes on the rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na(+),K(+))-ATPase and Mg(2+)-ATPase. Thirty-eight male Wistar rats were divided into six groups: C(A) (8-week-control), C(B) (8-week-control + 1-week-saline-treated), C + Cys (8-week-control + 1-week-Cys-treated), D(A) (8-week-diabetic), D(B) (8-week-diabetic + 1-week-saline-treated) and D + Cys (8-week-diabetic + 1-week-Cys-treated). All diabetic rats were once treated with an intraperitoneal (i.p.) STZ injection (50 mg/kg body weight) at the beginning of the experiment, while all Cys-treated groups received i.p. injections of Cys 7 mg/kg body weight (daily, for 1-week, during the 9th-week). Whole rat brain parameters were measured spectrophotometrically. In vitro incubation with 0.83 mM of Cys or 10 mM of STZ for 3 h was performed on brain homogenate samples from groups C(B) and D(B), in order to study the enzymes' activities. Diabetic rats exhibited a statistically significant reduction in brain TAS (-28%, D(A) vs C(A);-30%, D(B) vs C(B)) that was reversed after 1-week-Cys-administration into basal levels. Diabetes caused a significant increase in AChE activity (+27%, D(A) vs C(A); +15%, D(B) vs C(B)), that was further enhanced by Cys-administration (+57%, D + Cys vs C(B)). The C + Cys group exhibited no significant difference compared to the C(B) group in TAS (+2%), but showed a significantly increased AChE activity (+66%, C + Cys vs C(B)). Diabetic rats exhibited a significant reduction in the activity of Na(+),K(+)-ATPase (-36%, D(A) vs C(A);-48%, D(B) vs C(B)) that was not reversed after 1-week Cys administration. However, in vitro incubation with Cys partially reversed the diabetes-induced Na(+),K(+)-ATPase inhibition. Mg(2+)-ATPase activity was not affected by STZ-induced diabetes, while Cys caused a significant inhibition of the enzyme, both in vivo (-14%, C + Cys vs C(B);-17%, D + Cys vs C(B)) and in vitro (-16%, D(B) + in vitro Cys vs C(B)). In vitro incubation with STZ had no effect on the studied enzymes. The present data revealed a protective role for Cys towards the oxidative effect of diabetes on the adult rat brain. Moreover, an increase in whole brain AChE activity due to diabetes was recorded (not repeatedly established in the literature, since contradictory findings exist), that was further increased by Cys. The inhibition of Na(+),K(+)-ATPase reflects a possible mechanism through which untreated diabetes could affect neuronal excitability, metabolic energy production and certain systems of neurotransmission. As concerns the use of Cys as a neuroprotective agent against diabetes, our in vitro findings could be indicative of a possible protective role of Cys under different in vivo experimental conditions.

Lanthanum (La) is a rare earth element that is widely used for industrial, medical and agricultural purposes. Its neurotoxic effects are linked to its physical and chemical properties and its interaction with certain trace elements and membrane-bound enzymes. The aim of this study was to investigate the effects of short-term La-administration (as LaCl(3), 53 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, as well as the potential effect of the co-administration of the antioxidant L: -cysteine (Cys, 7 mg/kg) on the above parameters. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (La), C (Cys),and D (La 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 La exhibited a significant reduction in brain TAS (-36%, P < 0.001, BvsA), that was partially limited by the co-administration of Cys (-13%, P < 0.01, DvsA), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both La (+23%, P < 0.001, BvsA) and Cys (+59%, P < 0.001, CvsA), while it was adjusted to control levels by the co-administration of La and Cys. The activity of rat brain Na(+),K(+)-ATPase was significantly decreased by La-administration (-28%, P < 0.001, BvsA), while Cys supplementation could not reverse this decrease. The activity of Mg(2+)-ATPase exhibited a slight but statistically significant reduction due to La (-8%, P < 0.01, BvsA), that was further reduced by Cys co-administration (-25%, P < 0.001, DvsA). The above findings suggest that La 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 into control levels by Cys co-administration, which could thus be considered for future applications as a neuroprotective agent against chronic exposure to La. The activities of Na(+),K(+)- and Mg(2+)-ATPase that were inhibited by La, could not be reversed by Cys co-administration. A role for the already reported concentration-dependent interaction of La with Ca-binding sites (such as Ca(2+)-ATPase) might be considered for certain of the above phenomena.

Manganese (Mn) is an essential metalloenzyme component that in high doses can exert serious oxidative and neurotoxic effects. The aim of this study was to investigate the potential effect of the antioxidant L-cysteine (Cys, 7 mg/kg) on the adult rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na+,K+-ATPase and Mg2+-ATPase induced by short-term Mn administration (as Mn chloride, 50 mg/kg). Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Mn), C (Cys) and D (Mn and Cys). All rats were treated once daily, for 1 week with intraperitoneal injections of the tested compounds. Rats were killed by decapitation and mentioned parameters were measured spectrophotometrically. Rats treated with Mn exhibited a significant reduction in brain TAS (-39%, P0.001, B versus A) that was partially reversed by Cys co-administration (-13%, P0.01, D versus A), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both Mn (+21%, P0.001, B versus A) and Cys (+61%, P0.001, C versus A), while it was adjusted into the control levels by the co-administration of Mn and Cys. The activity of rat brain Na+,K+-ATPase was not affected by Mn administration, while Mg2+-ATPase exhibited a slight but statistically significant reduction in its activity (-9%, P0.01, B versus A) due to Mn, which was further reduced by Cys co-administration. The above findings suggest that short-term Mn 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 into the control levels by Cys co-administration (which could thus be considered for future applications as a neuroprotective agent against chronic exposure to Mn and the treatment of manganism). The activity of Na+,K+-ATPase is not affected by Mn, while Mg2+-ATPase activity is slightly (but significantly) inhibited by Mn, possibly due to Mg replacement.

Choline (Ch) is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions that affect the nervous system, while thioacetamide (TAA) is a well-known hepatotoxic agent. The induction of prolonged Ch-deprivation (CD) in rats receiving TAA (through the drinking water) provides an experimental model of mild progressive hepatotoxicity that could simulate commonly-presented cases in clinical practice. In this respect, the aim of this study was to investigate the effects of a 30-day dietary CD and/or TAA administration (300 mg/L of drinking water) on the serum total antioxidant status (TAS) and the activities of brain acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase of adult rats. Twenty male Wistar rats were divided into four groups: A (control), B (CD), C (TAA), D (CD+TAA). Dietary CD was provoked through the administration of Ch-deficient diet. Rats were sacrificed by decapitation at the end of the 30-day experimental period and whole brain enzymes were determined spectrophotometrically. Serum TAS was found significantly lowered by CD (-11% vs Control, p < 0.01) and CD+TAA administration (-19% vs Control, p < 0.001), but was not significantly altered due to TAA administration. The rat brain AChE activity was found significantly increased by TAA administration (+11% vs Control, p < 0.01), as well as by CD+TAA administration (+14% vs Control, p < 0.01). However, AChE was not found to be significantly altered by the 30-day dietary CD. On the other hand, CD caused a significant increase in brain Na(+),K(+)-ATPase activity (+16% vs Control, p < 0.05) and had no significant effect on Mg(2+)-ATPase. Exposure to TAA had no significant effect on Na(+),K(+)-ATPase, but inhibited Mg(2+)-ATPase (-20% vs Control, p < 0.05). When administered to CD rats, TAA caused a significant decrease in Na(+),K(+)-ATPase activity (-41% vs Control, p < 0.001), but Mg(2+)-ATPase activity was maintained into control levels. Our data revealed that an adult-onset 30-day dietary-induced CD had no effect on AChE activity. Treatment with TAA not only reversed the stimulatory effect of CD on adult rat brain Na(+),K(+)-ATPase, but caused a dramatic decrease in its activity (-41%). Previous studies have linked this inhibition with metabolic phenomena related to TAA-induced fulminant hepatic failure and encephalopathy. Our data suggest that CD (at least under the examined 30-day period) is an unfavorable background for the effect of TAA-induced hepatic damage on Na(+),K(+)-ATPase activity (an enzyme involved in neuronal excitability, metabolic energy production and neurotransmission).