ABSTRACT
Nicotine is the main alkaloid of tobacco and possesses well-established stimulant effects. Previous reports show that nicotine at low doses improves memory functions, while high doses impair memory. This study aims to analyze the effects of nicotine (NIC) on inhibitory avoidance task and on DNA damage, reactive oxygen species (ROS) concentration, total antioxidant capacity, and lipid peroxidation in cortex and hippocampus of old rats. Male Wistar rats of 24-26 months old (620-700g) were exposed i.p. to two doses (0.3 and 1mg/kg) of NIC daily during 9 days. The treatment NIC 0.3 enhanced long-term memory (p<0.05), whereas NIC 1 improved both short and long-term memories (p<0.05). DNA damage was observed only in hippocampus (p<0.05) after NIC 1 exposure. A similar result was obtained for ROS: higher levels were detected at NIC 1 treatment in hippocampus (p<0.05). No alterations in the total antioxidant capacity were verified after NIC exposure (0.3 and 1mg/kg) in both tissues (p>0.05). Finally, evidence of oxidative damage was observed in terms of lipid peroxides levels, being higher at NIC 1 in hippocampus (p<0.05). Overall the results indicate that deleterious effects paralleled the improved short and long-term memories at the highest NIC dose, since augmented DNA damage, ROS concentration and lipid peroxides levels were registered.
Subject(s)
Cerebral Cortex/drug effects , Cerebral Cortex/growth & development , Hippocampus/drug effects , Hippocampus/growth & development , Nicotine/pharmacology , Nicotine/toxicity , Nicotinic Agonists/pharmacology , Nicotinic Agonists/toxicity , Animals , Antioxidants/metabolism , Avoidance Learning/drug effects , Comet Assay , DNA Damage/drug effects , Free Radical Scavengers/metabolism , Lipid Peroxidation/drug effects , Lipid Peroxides/metabolism , Memory/drug effects , Memory, Short-Term/drug effects , Oxidative Stress/drug effects , Rats , Rats, Wistar , Reactive Oxygen Species/metabolismABSTRACT
Microcystins produced by cyanobacteria are potent inhibitors of some protein phosphatases, but recent evidence also indicates its potential to generate oxidative stress. In the present study, the effects of microcystin raw extracts (Mic; 0.01 and 20microg/L) and purified okadaic acid (OA; 0.01 and 10microg/L) on short- and long-term memory alteration and antioxidant and oxidative damage were investigated in hippocampus of rats. The results showed an amnesic effect with 0.01 and 20microg/L Mic on retrieval and only with 0.01microg/L Mic on spatial learning. Parallel to these effects oxidative damage was observed as evidenced by augmented levels of lipid peroxides and DNA damage and the absence of antioxidant responses in terms of total oxyradical scavenging capacity. Phase II reactions catalyzed by glutathione-S-transferase were not modified after microcystins exposure. Overall this study showed physiological events (retrieval and spatial learning) that can be related to the classical toxic effects of microcystins (i.e., phosphatase inhibition). In addition, evidence of alternative toxicity mechanisms via oxidative stress generation was also obtained. The fact that organic anion transporter polypeptides (OATP) involved in microcystins uptake are expressed not only in liver but also in brain points to the environmental relevance of the observed effects.
