Polyamines, among other functions, are considered to act as a free radical scavenger and antioxid... more Polyamines, among other functions, are considered to act as a free radical scavenger and antioxidant. The quinolinic acid (QA), sodium nitroprusside (SNP) and iron (Fe+2) stimulate production of free radicals and lipid peroxidation. In the present study, we investigated the free radical and/or aldehyde scavenger effects of polyamines spermine and spermidine on thiobarbituric acid reactive species (TBARS) production induced by QA, SNP, Fe+2/EDTA system and free Fe2+ in rat brain. Spermine and spermidine inhibited QA-induced TBARS production; however spermine was a better antioxidant than spermidine. Spermine also inhibited SNP-, Fe+2/EDTA- and free Fe2+-induced TBARS production, but had a modest effect. Spermidine, in turn, also discretely inhibited SNP-, Fe+2/EDTA- and free Fe2+-induced TBARS production. In the presence of MK-801, QA-induced TBARS production was considerably more inhibited by polyamines. In addition, arcaine does not affect the reducer effect of polyamines. The present findings suggest that the observed effects of polyamines are not related to the activation of NMDA receptor but with their antioxidant and free radical scavenger properties.
BackgroundLipopolysaccharide (LPS) induces neuroinflammation and memory deficit. Since polyamines... more BackgroundLipopolysaccharide (LPS) induces neuroinflammation and memory deficit. Since polyamines improve memory in various cognitive tasks, we hypothesized that spermine administration reverses LPS-induced memory deficits in an object recognition task in mice. The involvement of the polyamine binding site at the N-methyl-D-aspartate (NMDA) receptor and cytokine production in the promnesic effect of spermine were investigated.MethodsAdult male mice were injected with LPS (250 ¿g/kg, intraperitoneally) and spermine (0.3 to 1 mg/kg, intraperitoneally) or ifenprodil (0.3 to 10 mg/kg, intraperitoneally), or both, and their memory function was evaluated using a novel object recognition task. In addition, cortical and hippocampal cytokines levels were measured by ELISA four hours after LPS injection.ResultsSpermine increased but ifenprodil decreased the recognition index in the novel object recognition task. Spermine, at doses that did not alter memory (0.3 mg/kg, intraperitoneally), reve...
ABSTRACT Background We investigate behavioral tests, acetylcholinesterase (AChE) and Na+,K+-ATPas... more ABSTRACT Background We investigate behavioral tests, acetylcholinesterase (AChE) and Na+,K+-ATPase activities in rats with diet-induced hypercholesterolemia feeding and α-tocopherol administration.Methods We tested a protocol with four groups: standard diet (control); high-fat diet (HF); α-tocopherol (α-Toc); HF plus α-tocopherol (HF+α-Toc). HF was administered ad libitum and α-Toc (50 mg/kg) by gavage. After three months of treatment we performed the behavioral tests. The biochemical assays were performed ex vivo in the cerebral cortex (CC), hippocampus (HP) and blood samples.ResultsThe behavioral tests results showed a decrease in step-down latency for the HF group (P < 0.05). When rats that received HF were treated with α-toc (HF+α-Toc) the step-down latency was similar to the control group. AChE and Na+,K+-ATPase activities in homogenate and synaptosomes was observed a significant decrease in CC and HP in HF group (P < 0.05). However, α-Toc group showed to reverse the decline in AChE and Na+,K+-ATPase activities in CC and HP. HF group showed a significant increase (P < 0.05) in MDA levels in CC and HP in relation to other groups. However, α-Toc group showed a significant decrease (P < 0.05) in MDA levels when only compared with the HF group. Blood AChE activity increased in α-Toc group (P < 0.05) and decreased in HF group (P < 0.05) compared to all groups.Conclusions The present outcomes showed that treatment with α-Toc prevents the inhibition of AChE and Na+,K+-ATPase activities and consequently memory impairment induced by HF diet, demonstrating that this compound can modulate cholinergic neurotransmission and consequently improve cognition in this experimental condition.
The international journal of biochemistry & cell biology, 2003
The effects of the administration of monosialoganglioside (GM1) on methylmalonic acid (MMA)-induc... more The effects of the administration of monosialoganglioside (GM1) on methylmalonic acid (MMA)-induced convulsions, production of thiobarbituric acid reactive substances (TBARS) and on the striatal content of ascorbic acid and total non-protein thiol (SH) groups were evaluated in adult male rats. Animals received two intraperitoneal injections of GM1 (50 mg/kg) or saline (0.85% NaCl) spaced 24h apart. Thirty minutes after the second GM1 or saline injection, L-MMA (6 micromol) or NaCl (9 micromol) was injected into the right striatum and the animals were observed for the appearance of convulsions for 15 min. The animals were sacrificed and their striatal content of ascorbic acid, SH groups and TBARS was measured. The effect of GM1 on MMA-induced TBARS production in striatal homogenates was also evaluated in vitro.MMA injection caused convulsions (Sal-MMA: 9.8+/-1.4 episodes, which lasted 271+/-48 s) and increased the striatal content of TBARS (Sal-MMA: 149.0+/-11.5 nmol MDA/g tissue), b...
Arcaine is a competitive antagonist of the polyamine binding site at the N-methyl-D-aspartic acid... more Arcaine is a competitive antagonist of the polyamine binding site at the N-methyl-D-aspartic acid receptor which induces state-dependent recall. However, no study has addressed the involvement of other neurotransmitter/neuromodulators in arcaine-induced state dependency. The current study investigates whether the opioid system is involved in arcaine-induced state-dependent memory retrieval of the inhibitory avoidance task (IA) in rats. The systemic administration of arcaine (30 mg/kg, intraperitoneally (i.p.)) or morphine (5 mg/kg, i.p.) 0, 3, 6, or 9 h post-training, reduced step-down latencies at testing. Arcaine (30 mg/kg, i.p.) or morphine (5 mg/kg, i.p.) injection 30 min before testing reversed the performance deficit induced by administration of arcaine or morphine 0, 3 or 6, but not 9 h post-training. The reversal of arcaine-induced impairment of IA performance was completely transferred to morphine and vice versa. The association of low and ineffective doses of morphine and arcaine (10 and 1.5 mg/kg, respectively) were additive and caused state dependency. Naloxone (2 mg/kg, 3 min post-training, or 1 mg/kg, 1 h pre-test, i.p.) reversed the amnesia and the state dependency induced by morphine and arcaine. These results suggest that state dependency induced by arcaine involves the opioid system.
The polyamines putrescine, spermidine, and spermine are a group of aliphatic amines that may act ... more The polyamines putrescine, spermidine, and spermine are a group of aliphatic amines that may act as physiological modulators of the N-methyl-D-aspartate (NMDA) receptor, a glutamate receptor implicated in memory formation and consolidation. Arcaine is a competitive antagonist of the polyamine binding site at the NMDA receptor, the post-training administration of which impairs memory of various tasks. In this study, we investigated whether the administration of arcaine and MK-801 alters the memory of the step-down inhibitory avoidance task, and whether the effects of these NMDA antagonists involve state-dependency mechanisms, in adult male Wistar rats. The administration of arcaine (30 mg/kg, i.p.) or MK-801 (0.03 mg/kg, i.p.) immediately after training impaired inhibitory avoidance performance at testing. Arcaine- and MK-801-induced performance impairment was reversed by the administration of arcaine (30 mg/kg, i.p.) and MK-801 (0.03 mg/kg, i.p.), respectively, 30 min before testing. Response transfer also occurred if arcaine substituted MK-801 at testing, and vice-versa. These results suggest that arcaine and MK-801 induce state-dependent recall and that, probably due to their ability to decrease NMDA receptor function, one drug can substitute for the other at testing, demonstrating a cross-state dependency between arcaine and MK-801.
Previous studies have demonstrated that post-training intrahippocampal glutamate administration i... more Previous studies have demonstrated that post-training intrahippocampal glutamate administration improves inhibitory avoidance task performance in rats. Antagonism of the agonist actions of glutamate by guanine nucleotides has been shown at the molecular and behavioural level. In the present investigation we demonstrate that intrahippocampal co-administration of GMP (guanosine 5'-monophosphate) reverses the facilitatory effect of glutamate on the inhibitory avoidance learning paradigm and inhibits [3H]glutamate binding in hippocampal synaptic plasma membranes. These results suggest that guanine nucleotides may modulate glutamate actions.
It is well known that the levels of adenosine in the brain increase dramatically during cerebral ... more It is well known that the levels of adenosine in the brain increase dramatically during cerebral hypoxic-ischemic (HI) insults. Its levels are tightly regulated by physiological and pathophysiological changes that occur during the injury acute phase. The aim of the present study was to examine the effects of the neonatal HI event on cytosolic and ecto-enzymes of purinergic system--NTPDase, 5'-nucleotidase (5'-NT) and adenosine deaminase (ADA)--in cerebral cortex of rats immediately post insult. Furthermore, the Na(+)/K(+)-ATPase activity, adenosine kinase (ADK) expression and thiobarbituric acid reactive species (TBARS) levels were assessed. Immediately after the HI event the cytosolic NTPDase and 5'-NT activities were increased in the cerebral cortex. In synaptosomes there was an increase in the ecto-ADA activity while the Na(+)/K(+) ATPase activity presented a decrease. The difference between ATP, ADP, AMP and adenosine degradation in synaptosomal and cytosolic fractions could indicate that NTPDase, 5'-NT and ADA were differently affected after insult. Interestingly, no alterations in the ADK expression were observed. Furthermore, the Na(+)/K(+)-ATPase activity was correlated negatively with the cytosolic NTPDase activity and TBARS content. The increased hydrolysis of nucleotides ATP, ADP and AMP in the cytosol could contribute to increased adenosine levels, which could be related to a possible innate neuroprotective mechanism aiming at potentiating the ambient levels of adenosine. Together, these results may help the understanding of the mechanism by which adenosine is produced following neonatal HI injury, therefore highlighting putative therapeutical targets to minimize ischemic injury and enhance recovery.
Spermidine (SPD) is an endogenous polyamine that modulates N-methyl-D-aspartate (NMDA) receptor f... more Spermidine (SPD) is an endogenous polyamine that modulates N-methyl-D-aspartate (NMDA) receptor function, and has been reported to facilitate memory formation. In the current study we determined whether or not the PKA/CREB signaling pathway is involved in SPD-induced facilitation of memory of inhibitory avoidance task in adult rats. The post-training administration of the cAMP-dependent protein kinase (PKA) inhibitor, N-[2-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide [H-89, 0.5 ρmol intrahippocampal (ih)] or the antagonist of the NMDA receptor polyamine-binding site (arcaine, 0.02 nmol ih) with SPD (0.2 nmol ih) prevented memory improvement induced by SPD. Intrahippocampal administration of SPD (0.2 nmol) facilitated PKA and cAMP response element-binding protein (CREB) phosphorylation in the hippocampus 180 min, but not 30 min, after administration, and increased translocation of the catalytic subunit of PKA into the nucleus. Arcaine (0.02 nmol) and H-89 (0.5 ρmol) prevented the stimulatory effect of SPD on PKA and CREB phosphorylation. These results suggest that memory enhancement induced by the ih administration of SPD involves the PKA/CREB pathways in rats.
Cigarette smoke-exposure promotes neurobiological changes associated with neurocognitive abnormal... more Cigarette smoke-exposure promotes neurobiological changes associated with neurocognitive abnormalities. Curcumin, a natural polyphenol, have shown to be able to prevent cigarette smoke-induced cognitive impairment. Here, we investigated possible mechanisms involved in curcumin protection against cigarette smoke-induced cognitive impairment and, due to its poor bioavailability, we investigated the potential of using curcumin-loaded lipid-core nanocapsules (C-LNC) suspension. Rats were treated with curcumin and cigarette smoke, once a day, 5 days each week, for 30 days. Animals were divided into ten groups: I, control (vehicle/corn oil); II, curcumin 12.5mg/kg; III, curcumin 25mg/kg; IV, curcumin 50mg/kg; V, C-LNC 4 mg/kg; VI, tobacco exposed; VII, curcumin 12.5mg/kg along with tobacco exposure; VIII, curcumin 25mg/kg along with tobacco exposure; IX, curcumin 50mg/kg along with tobacco exposure; X, C-LNC 4 mg/kg along with tobacco exposure. Cigarette smoke-exposure impaired object recognition memory (P<0.001), indicated by the low recognition index, increased biomarkers of oxidative/nitrosative stress such as TBARS (P<0.05) and NOx (P<0.01), decreased antioxidant defenses such as NPSH content (P<0.01) and SOD activity (P<0.01) and inhibited the activities of enzymes involved in ion homeostasis such as Na(+),K(+)-ATPase and Ca(2+)-ATPase. Both curcumin formulations (free and nanoencapsulated) prevented the memory impairment, the redox imbalance and the alterations observed in the ATPases activities. Maintenance of ion homeostasis and redox balance is involved in the protective mechanism of curcumin against tobacco-induced cognitive impairment. Our results suggest that curcumin is a potential therapeutic agent for neurocognition and that C-LNC may be an alternative to its poor bioavailability.
Polyamines, among other functions, are considered to act as a free radical scavenger and antioxid... more Polyamines, among other functions, are considered to act as a free radical scavenger and antioxidant. The quinolinic acid (QA), sodium nitroprusside (SNP) and iron (Fe+2) stimulate production of free radicals and lipid peroxidation. In the present study, we investigated the free radical and/or aldehyde scavenger effects of polyamines spermine and spermidine on thiobarbituric acid reactive species (TBARS) production induced by QA, SNP, Fe+2/EDTA system and free Fe2+ in rat brain. Spermine and spermidine inhibited QA-induced TBARS production; however spermine was a better antioxidant than spermidine. Spermine also inhibited SNP-, Fe+2/EDTA- and free Fe2+-induced TBARS production, but had a modest effect. Spermidine, in turn, also discretely inhibited SNP-, Fe+2/EDTA- and free Fe2+-induced TBARS production. In the presence of MK-801, QA-induced TBARS production was considerably more inhibited by polyamines. In addition, arcaine does not affect the reducer effect of polyamines. The present findings suggest that the observed effects of polyamines are not related to the activation of NMDA receptor but with their antioxidant and free radical scavenger properties.
BackgroundLipopolysaccharide (LPS) induces neuroinflammation and memory deficit. Since polyamines... more BackgroundLipopolysaccharide (LPS) induces neuroinflammation and memory deficit. Since polyamines improve memory in various cognitive tasks, we hypothesized that spermine administration reverses LPS-induced memory deficits in an object recognition task in mice. The involvement of the polyamine binding site at the N-methyl-D-aspartate (NMDA) receptor and cytokine production in the promnesic effect of spermine were investigated.MethodsAdult male mice were injected with LPS (250 ¿g/kg, intraperitoneally) and spermine (0.3 to 1 mg/kg, intraperitoneally) or ifenprodil (0.3 to 10 mg/kg, intraperitoneally), or both, and their memory function was evaluated using a novel object recognition task. In addition, cortical and hippocampal cytokines levels were measured by ELISA four hours after LPS injection.ResultsSpermine increased but ifenprodil decreased the recognition index in the novel object recognition task. Spermine, at doses that did not alter memory (0.3 mg/kg, intraperitoneally), reve...
ABSTRACT Background We investigate behavioral tests, acetylcholinesterase (AChE) and Na+,K+-ATPas... more ABSTRACT Background We investigate behavioral tests, acetylcholinesterase (AChE) and Na+,K+-ATPase activities in rats with diet-induced hypercholesterolemia feeding and α-tocopherol administration.Methods We tested a protocol with four groups: standard diet (control); high-fat diet (HF); α-tocopherol (α-Toc); HF plus α-tocopherol (HF+α-Toc). HF was administered ad libitum and α-Toc (50 mg/kg) by gavage. After three months of treatment we performed the behavioral tests. The biochemical assays were performed ex vivo in the cerebral cortex (CC), hippocampus (HP) and blood samples.ResultsThe behavioral tests results showed a decrease in step-down latency for the HF group (P < 0.05). When rats that received HF were treated with α-toc (HF+α-Toc) the step-down latency was similar to the control group. AChE and Na+,K+-ATPase activities in homogenate and synaptosomes was observed a significant decrease in CC and HP in HF group (P < 0.05). However, α-Toc group showed to reverse the decline in AChE and Na+,K+-ATPase activities in CC and HP. HF group showed a significant increase (P < 0.05) in MDA levels in CC and HP in relation to other groups. However, α-Toc group showed a significant decrease (P < 0.05) in MDA levels when only compared with the HF group. Blood AChE activity increased in α-Toc group (P < 0.05) and decreased in HF group (P < 0.05) compared to all groups.Conclusions The present outcomes showed that treatment with α-Toc prevents the inhibition of AChE and Na+,K+-ATPase activities and consequently memory impairment induced by HF diet, demonstrating that this compound can modulate cholinergic neurotransmission and consequently improve cognition in this experimental condition.
The international journal of biochemistry & cell biology, 2003
The effects of the administration of monosialoganglioside (GM1) on methylmalonic acid (MMA)-induc... more The effects of the administration of monosialoganglioside (GM1) on methylmalonic acid (MMA)-induced convulsions, production of thiobarbituric acid reactive substances (TBARS) and on the striatal content of ascorbic acid and total non-protein thiol (SH) groups were evaluated in adult male rats. Animals received two intraperitoneal injections of GM1 (50 mg/kg) or saline (0.85% NaCl) spaced 24h apart. Thirty minutes after the second GM1 or saline injection, L-MMA (6 micromol) or NaCl (9 micromol) was injected into the right striatum and the animals were observed for the appearance of convulsions for 15 min. The animals were sacrificed and their striatal content of ascorbic acid, SH groups and TBARS was measured. The effect of GM1 on MMA-induced TBARS production in striatal homogenates was also evaluated in vitro.MMA injection caused convulsions (Sal-MMA: 9.8+/-1.4 episodes, which lasted 271+/-48 s) and increased the striatal content of TBARS (Sal-MMA: 149.0+/-11.5 nmol MDA/g tissue), b...
Arcaine is a competitive antagonist of the polyamine binding site at the N-methyl-D-aspartic acid... more Arcaine is a competitive antagonist of the polyamine binding site at the N-methyl-D-aspartic acid receptor which induces state-dependent recall. However, no study has addressed the involvement of other neurotransmitter/neuromodulators in arcaine-induced state dependency. The current study investigates whether the opioid system is involved in arcaine-induced state-dependent memory retrieval of the inhibitory avoidance task (IA) in rats. The systemic administration of arcaine (30 mg/kg, intraperitoneally (i.p.)) or morphine (5 mg/kg, i.p.) 0, 3, 6, or 9 h post-training, reduced step-down latencies at testing. Arcaine (30 mg/kg, i.p.) or morphine (5 mg/kg, i.p.) injection 30 min before testing reversed the performance deficit induced by administration of arcaine or morphine 0, 3 or 6, but not 9 h post-training. The reversal of arcaine-induced impairment of IA performance was completely transferred to morphine and vice versa. The association of low and ineffective doses of morphine and arcaine (10 and 1.5 mg/kg, respectively) were additive and caused state dependency. Naloxone (2 mg/kg, 3 min post-training, or 1 mg/kg, 1 h pre-test, i.p.) reversed the amnesia and the state dependency induced by morphine and arcaine. These results suggest that state dependency induced by arcaine involves the opioid system.
The polyamines putrescine, spermidine, and spermine are a group of aliphatic amines that may act ... more The polyamines putrescine, spermidine, and spermine are a group of aliphatic amines that may act as physiological modulators of the N-methyl-D-aspartate (NMDA) receptor, a glutamate receptor implicated in memory formation and consolidation. Arcaine is a competitive antagonist of the polyamine binding site at the NMDA receptor, the post-training administration of which impairs memory of various tasks. In this study, we investigated whether the administration of arcaine and MK-801 alters the memory of the step-down inhibitory avoidance task, and whether the effects of these NMDA antagonists involve state-dependency mechanisms, in adult male Wistar rats. The administration of arcaine (30 mg/kg, i.p.) or MK-801 (0.03 mg/kg, i.p.) immediately after training impaired inhibitory avoidance performance at testing. Arcaine- and MK-801-induced performance impairment was reversed by the administration of arcaine (30 mg/kg, i.p.) and MK-801 (0.03 mg/kg, i.p.), respectively, 30 min before testing. Response transfer also occurred if arcaine substituted MK-801 at testing, and vice-versa. These results suggest that arcaine and MK-801 induce state-dependent recall and that, probably due to their ability to decrease NMDA receptor function, one drug can substitute for the other at testing, demonstrating a cross-state dependency between arcaine and MK-801.
Previous studies have demonstrated that post-training intrahippocampal glutamate administration i... more Previous studies have demonstrated that post-training intrahippocampal glutamate administration improves inhibitory avoidance task performance in rats. Antagonism of the agonist actions of glutamate by guanine nucleotides has been shown at the molecular and behavioural level. In the present investigation we demonstrate that intrahippocampal co-administration of GMP (guanosine 5'-monophosphate) reverses the facilitatory effect of glutamate on the inhibitory avoidance learning paradigm and inhibits [3H]glutamate binding in hippocampal synaptic plasma membranes. These results suggest that guanine nucleotides may modulate glutamate actions.
It is well known that the levels of adenosine in the brain increase dramatically during cerebral ... more It is well known that the levels of adenosine in the brain increase dramatically during cerebral hypoxic-ischemic (HI) insults. Its levels are tightly regulated by physiological and pathophysiological changes that occur during the injury acute phase. The aim of the present study was to examine the effects of the neonatal HI event on cytosolic and ecto-enzymes of purinergic system--NTPDase, 5'-nucleotidase (5'-NT) and adenosine deaminase (ADA)--in cerebral cortex of rats immediately post insult. Furthermore, the Na(+)/K(+)-ATPase activity, adenosine kinase (ADK) expression and thiobarbituric acid reactive species (TBARS) levels were assessed. Immediately after the HI event the cytosolic NTPDase and 5'-NT activities were increased in the cerebral cortex. In synaptosomes there was an increase in the ecto-ADA activity while the Na(+)/K(+) ATPase activity presented a decrease. The difference between ATP, ADP, AMP and adenosine degradation in synaptosomal and cytosolic fractions could indicate that NTPDase, 5'-NT and ADA were differently affected after insult. Interestingly, no alterations in the ADK expression were observed. Furthermore, the Na(+)/K(+)-ATPase activity was correlated negatively with the cytosolic NTPDase activity and TBARS content. The increased hydrolysis of nucleotides ATP, ADP and AMP in the cytosol could contribute to increased adenosine levels, which could be related to a possible innate neuroprotective mechanism aiming at potentiating the ambient levels of adenosine. Together, these results may help the understanding of the mechanism by which adenosine is produced following neonatal HI injury, therefore highlighting putative therapeutical targets to minimize ischemic injury and enhance recovery.
Spermidine (SPD) is an endogenous polyamine that modulates N-methyl-D-aspartate (NMDA) receptor f... more Spermidine (SPD) is an endogenous polyamine that modulates N-methyl-D-aspartate (NMDA) receptor function, and has been reported to facilitate memory formation. In the current study we determined whether or not the PKA/CREB signaling pathway is involved in SPD-induced facilitation of memory of inhibitory avoidance task in adult rats. The post-training administration of the cAMP-dependent protein kinase (PKA) inhibitor, N-[2-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide [H-89, 0.5 ρmol intrahippocampal (ih)] or the antagonist of the NMDA receptor polyamine-binding site (arcaine, 0.02 nmol ih) with SPD (0.2 nmol ih) prevented memory improvement induced by SPD. Intrahippocampal administration of SPD (0.2 nmol) facilitated PKA and cAMP response element-binding protein (CREB) phosphorylation in the hippocampus 180 min, but not 30 min, after administration, and increased translocation of the catalytic subunit of PKA into the nucleus. Arcaine (0.02 nmol) and H-89 (0.5 ρmol) prevented the stimulatory effect of SPD on PKA and CREB phosphorylation. These results suggest that memory enhancement induced by the ih administration of SPD involves the PKA/CREB pathways in rats.
Cigarette smoke-exposure promotes neurobiological changes associated with neurocognitive abnormal... more Cigarette smoke-exposure promotes neurobiological changes associated with neurocognitive abnormalities. Curcumin, a natural polyphenol, have shown to be able to prevent cigarette smoke-induced cognitive impairment. Here, we investigated possible mechanisms involved in curcumin protection against cigarette smoke-induced cognitive impairment and, due to its poor bioavailability, we investigated the potential of using curcumin-loaded lipid-core nanocapsules (C-LNC) suspension. Rats were treated with curcumin and cigarette smoke, once a day, 5 days each week, for 30 days. Animals were divided into ten groups: I, control (vehicle/corn oil); II, curcumin 12.5mg/kg; III, curcumin 25mg/kg; IV, curcumin 50mg/kg; V, C-LNC 4 mg/kg; VI, tobacco exposed; VII, curcumin 12.5mg/kg along with tobacco exposure; VIII, curcumin 25mg/kg along with tobacco exposure; IX, curcumin 50mg/kg along with tobacco exposure; X, C-LNC 4 mg/kg along with tobacco exposure. Cigarette smoke-exposure impaired object recognition memory (P<0.001), indicated by the low recognition index, increased biomarkers of oxidative/nitrosative stress such as TBARS (P<0.05) and NOx (P<0.01), decreased antioxidant defenses such as NPSH content (P<0.01) and SOD activity (P<0.01) and inhibited the activities of enzymes involved in ion homeostasis such as Na(+),K(+)-ATPase and Ca(2+)-ATPase. Both curcumin formulations (free and nanoencapsulated) prevented the memory impairment, the redox imbalance and the alterations observed in the ATPases activities. Maintenance of ion homeostasis and redox balance is involved in the protective mechanism of curcumin against tobacco-induced cognitive impairment. Our results suggest that curcumin is a potential therapeutic agent for neurocognition and that C-LNC may be an alternative to its poor bioavailability.
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