Effects of acute and chronic cadmium administration on the vascular reactivity of rat aorta.

The effect of acute and chronic cadmium (Cd) administration on the vascular function of the rat aorta was studied. The rats were randomly divided into four main groups (A: saline controls under chronic administration, B: Cd-treated rats under chronic administration, C: saline controls under acute administration, D: Cd-treated rats under acute administration). After their sacrifice, the aortic rings were divided into rings with endothelium (E+) and without (E-), and suspended in an isolated organ bath with Krebs - Henseleit buffer. Maximal tension (T max, in g) was measured in response to potassium chloride (KCl) and phenylephrine (PE) in all aortic rings. Relaxation response to acetylcholine (ACh) administration was expressed as percent of maximal tension induced by PE. Chronic administration: A statistically significant increase of the contraction was observed between groups B (i.m. Cd 0.5 mg/kg for 120 days) and A (i.m. 0.9% NaCl for 120 days) in response to KCl (20-60 mM) and the T max as well (in both the E+ and the E- subgroups). No statistically significant difference was observed in response to PE and ACh exposure. Acute administration: A statistically significant increase was observed between group D(E+) (i.m. Cd 2 mg/kg, 8 h before sacrifice) and group C(E+) (i.m. 0.9% NaCl, 8 h before sacrifice) in response to 10-30 mM of KCl, and a significant decrease between D(E-) and C(E-) in response to 10(-7)-10(-6) M of PE, though T (max) was increased between D(E-) and C(E-) with PE exposure. The contractile response levels of the E+ aortic rings to PE and ACh showed no statistically significant difference.

Cadmium effects on brain acetylcholinesterase activity and antioxidant status of adult rats: modulation by zinc, calcium and L-cysteine co-administration.

We have previously reported that cadmium (Cd) as 3CdSO4 . 8H2O decreases rat brain total antioxidant status and L-cysteine (Cys) has a protective effect against it. The aim of the present study was to investigate the effects of subacute Cd administration, either alone or (almost simultaneously) with zinc (Zn), calcium (Ca) and Cys, on brain acetylcholinesterase (AChE) activity and brain total antioxidant status in male adult rats. All substances were administered intraperitoneally. Cadmium (1 mg/kg/day for 14 days) increased AChE activity (+46%; P<0.001) and decreased total antioxidant status (-29%; P<0.001). Zinc and Ca (both 1 mg/kg/day for 14 days) increased AChE activity (+18%; P<0.01 and +53%; P<0.001) and caused no changes on rat brain total antioxidant status. L-Cysteine (7 mg/kg/day for 14 days) impressively increased AChE activity (+185%; P<0.001) and augmented total antioxidant status (+26%; P<0.001). In the groups of Zn+Cd, Ca+Cd and Cys+Cd co-administration, AChE activity remained high (+42%; P<0.001, +41%; P<0.001 and +141%; P<0.001 respectively), while total antioxidant status returned to the saline control levels. L-Cysteine given before a toxic dose of Cd (5 mg/kg) resulted in high AChE activity (+85%; P<0.001), a total antioxidant status similar to the control values, and survival of the treated rats. In conclusion, Cd increased brain AChE activity and decreased brain total antioxidant status of adult male rats. Zinc, Ca and Cys, given just before Cd administration, modified the Cd-induced effects and restored rat brain total antioxidant status to the control levels.

In vivo and in vitro effects of cadmium on adult rat brain total antioxidant status, acetylcholinesterase, (Na+, K+)-ATPase and Mg2+-ATPase activities: protection by L-cysteine.

This study was undertaken in order to investigate a) the short- and long-term in vivo effects of cadmium (Cd) on brain acetylcholinesterase (AChE), (Na+, K+)-ATPase activities in adult rats, b) the concentration-dependent in vitro and in vivo (acute experiment) effects of Cd on the activity of those enzymes, c) the in vivo and in vitro effects of the antioxidant L-cysteine (Cys) on the above enzyme activities, and d) the evaluation of brain total antioxidant status after in vivo Cd, L-cysteine, or L-cysteine+Cd administration in rats. In vitro, CdSO4 inhibited pure and brain AChE in concentrations higher than 0.1 mM, while it activated by approximately 70% (P<0.001) brain Na+, K+ -ATPase in concentrations up to 0.1 mM and inhibited its activity in higher concentrations. Mg2+ -ATPase was not influenced up to 0.1 mM concentration, while it was inactivated (40%, P<0.001) in higher CdSO4 concentrations. A dose-response study of brain CdSO4 (1,2 and 5 mg/kg once 8 hr before decapitation) revealed a dose-dependent decrease (-14 to -30%, P<0.001) of brain AChE activity, an increase of Na+, K+ -ATPase activity (+47 to +200%, P<0.001) and an increase of Mg2+ -ATPase only after the highest dose (5mg/kg) in the short-term treatment of rats. Long-term Cd administration (1 mg/kg rat daily for 4 months) activated brain AChE and Na+, K+ -ATPase about 50-65% (P<0.001) but not Mg2+ -ATPase. Brain total antioxidant status was decreased by Cd (30%, P<0.01), while it was increased by L-cysteine or L-cysteine+Cd (50%, P<0.001) in the short-term in vivo treatment. L-cysteine reversed the enzymatic activity changes observed with Cd alone in the high-dose short-term in vivo treatment of rats, as well as the brain AChE inhibition induced by Cd in the in vitro experiments. These results indicate that: a) Cd can influence in a different way the examined enzyme activities after short- and long-term administration, b) Cd may modulate brain cholinergic mechanism(s), neural excitability and metabolic energy production, and c) L-cysteine can have a protective antioxidant effect on the oxidative stress of the brain induced by Cd.