Ação preventiva do cobre sobre alterações bioquímicas e comportamentais induzidas pelo mercúrio em ratos jovens

Abstract

This work examined the effectiveness of Cu pre-exposition on biochemical and behavioral changes induced by Hg exposure in young rats treated subcutaneously with saline or CuCl2.2H2O (Cu 2.6 mg/kg/day) from 3 to 7 days old and with saline or HgCl2 (Hg 3.7 mg/kg/day) from 8 to 12 days old. Tissue samples from animals killed 24 h or 21 days after the end of mercury exposure (13 or 33 days old) were used to analyze of blood, liver, kidney and cerebrum δ-aminolevulinic acid dehydratase (δ-ALA-D) activity; cerebrum and cerebellum acetylcholinesterase (AChE) activity; biochemical parameters indicative of hepatic and renal toxicity; and to determination of hepatic and renal metallothionein and metal levels (Hg, Cu, Zn, Fe e Mg) in all tissues studied. The animals also were submitted to behavioral tasks: negative geotaxis task (3, 5. 7, 9, 11 and 13 days old), tail immersion (13, 20 and 27 days old), rotarod tests (25 and 30 days old) and beaker test (17 to 20 days old). Mercury exposure reduced body and cerebrum and increased kidney weight; inhibited the hepatic and renal δ-ALA-D, cerebellum AChE and serum LDH activity; and increased serum urea and creatinine and hepatic MT levels at 13 days. The Hg effect persisted on body and renal weight, renal δ-ALA-D activity and urea levels checked after 33 days. Still, Hg exposure caused accumulation of this metal in all tissues analyzed; increased hepatic Zn and Fe levels; and decreased renal Fe and increased Cu levels at 13 days. The effect persisted on hepatic Hg levels; and renal Hg and Fe levels. In addition, a decrease in the liver weight and renal Mg levels; and increase in the cerebrum and cerebellum Zn levels were observed only at 33 days. In behavioral tasks, rats exposed to Hg presented impartment in motor function and muscular strength verified in the negative geotaxis task and beaker test. The Cu effectiveness as preventive treatment was immediate on parameters such as cerebellum AChE activity, serum creatinine levels, Hg content and homeostasis of hepatic Fe levels. The prevention of altered parameters as body, Kidney and liver weight, renal δ-ALA-D activity, serum urea levels and homeostasis of renal Fe and Mg levels were verified at 33 days. Behavioral changes were completely prevented by Cu pre-exposure. Moreover, Cu pre-exposure caused an important redistribution of Hg decreasing hepatic and sanguine Hg levels and increasing renal levels of 13-day-old rats. This effect occurred in parallel with an increase in MT levels in liver and kidney, suggesting that hepatic MT can bind to Hg and transporting this metal to the kidney in order to be excreted. The results of the present study suggest that Cu can be considered as potential preventive therapeutic agent against Hg toxicity, even when were evaluated later.