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Epicatechin Reduces Striatal MPP⁺-Induced Damage in Rats through Slight Increases in SOD-Cu,Zn Activity.

Rubio-Osornio M, Gorostieta-Salas E, Montes S, Pérez-Severiano F, Rubio C, Gómez C, Ríos C, Guevara J - Oxid Med Cell Longev (2015)

Bottom Line: Cu/Zn-dependent superoxide dismutase (Cu/Zn-SOD) activity was significantly (P < 0.05) reduced as a consequence of MPP(+) damage.Such effects persisted in animals injured with MPP(+).The results show that EC is effective against MPP(+)-induced biochemical and behavioral damage, which is possible by an increase in Cu/Zn-SOD activity.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, 14269 Mexico City, Mexico.

ABSTRACT
Parkinson's disease is a neurodegenerative disorder characterized by movement alterations caused by reduced dopaminergic neurotransmission in the nigrostriatal pathway, presumably by oxidative stress (OS). MPP(+) intrastriatal injection leads to the overproduction of free radicals (FR). The increasing formation of FR produces OS, a decline in dopamine (DA) content, and behavioral disorders. Epicatechin (EC) has shown the ability to be FR scavenger, an antioxidant enzyme inductor, a redox state modulator, and transition metal chelator. Acute administration of 100 mg/kg of EC significantly prevented (P < 0.05) the circling MPP(+)-induced behavior (10 μg/8 μL). Likewise, EC significantly (P < 0.05) reduced the formation of fluorescent lipid products caused by MPP(+). MPP(+) injection produced (P < 0.05) increased enzymatic activity of the constitutive nitric oxide synthase (cNOS). This effect was blocked with acute EC pretreatment. Cu/Zn-dependent superoxide dismutase (Cu/Zn-SOD) activity was significantly (P < 0.05) reduced as a consequence of MPP(+) damage. EC produced a slight increase (≈20%) in Cu/Zn-SOD activity in the control group. Such effects persisted in animals injured with MPP(+). The results show that EC is effective against MPP(+)-induced biochemical and behavioral damage, which is possible by an increase in Cu/Zn-SOD activity.

No MeSH data available.


Related in: MedlinePlus

Effect of oral 100 mg/kg epicatechin (EC) on circling behavior and striatal dopamine content in MPP+ model. (a) Six days after MPP+-induced damage, the EC effect on apomorphine-induced circling behavior was evaluated. The results are expressed as mean ± S.M.E. of 6–8 animals per group. ∗P < 0.05; data were analyzed by Kruskal-Wallis' test followed by U Mann-Whitney's test. (b) Twenty-four hours after the behavioral test evaluation, dopamine was determined by HPLC coupled to an electrochemical detector. Results are expressed as mean ± S.E.M. of 6–8 animals per group. ∗P < 0.01, two-way ANOVA followed by Tukey's test.
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fig1: Effect of oral 100 mg/kg epicatechin (EC) on circling behavior and striatal dopamine content in MPP+ model. (a) Six days after MPP+-induced damage, the EC effect on apomorphine-induced circling behavior was evaluated. The results are expressed as mean ± S.M.E. of 6–8 animals per group. ∗P < 0.05; data were analyzed by Kruskal-Wallis' test followed by U Mann-Whitney's test. (b) Twenty-four hours after the behavioral test evaluation, dopamine was determined by HPLC coupled to an electrochemical detector. Results are expressed as mean ± S.E.M. of 6–8 animals per group. ∗P < 0.01, two-way ANOVA followed by Tukey's test.

Mentions: The evaluation of the apomorphine-induced behavioral test was carried out 6 days after damage induced by MPP+. In a pilot experiment to select the dose and the time to inject the EC, we observed that a subchronic oral dose of 40, 60, and 80 mg/kg of EC for 5 days was not able to reduce the turning behavior induced by MPP+ (308 ± 28 ipsilateral turns) (data not shown). The subchronic dose of 100 mg/kg for five days reduced the turning behavior after MPP+ to 204.1 ± 20.7, ipsilateral turns/60 min. This effect was not different from a similar, previous dose of EC given 5 h before the MPP+ injury (data not shown). We therefore evaluated the effect of an acute dose of 100 mg/kg of EC administrated 5 h before the damage was induced by MPP+ and then 6 days after the circling behavior was induced by apomorphine. The results indicated that a single acute oral EC dose of 100 mg/kg significantly reduced (P < 0.05) the circling behavior (213.3 ± 24.94, ipsilateral turns/60 min) related to the damage induced by MPP+ (314.4 ± 29.87, ipsilateral turns/60 min). Single EC oral dose administration partially prevented the unbalanced turning behavior in MPP+-treated rats (Figure 1(a)) in the same manner as the chronic oral administration.


Epicatechin Reduces Striatal MPP⁺-Induced Damage in Rats through Slight Increases in SOD-Cu,Zn Activity.

Rubio-Osornio M, Gorostieta-Salas E, Montes S, Pérez-Severiano F, Rubio C, Gómez C, Ríos C, Guevara J - Oxid Med Cell Longev (2015)

Effect of oral 100 mg/kg epicatechin (EC) on circling behavior and striatal dopamine content in MPP+ model. (a) Six days after MPP+-induced damage, the EC effect on apomorphine-induced circling behavior was evaluated. The results are expressed as mean ± S.M.E. of 6–8 animals per group. ∗P < 0.05; data were analyzed by Kruskal-Wallis' test followed by U Mann-Whitney's test. (b) Twenty-four hours after the behavioral test evaluation, dopamine was determined by HPLC coupled to an electrochemical detector. Results are expressed as mean ± S.E.M. of 6–8 animals per group. ∗P < 0.01, two-way ANOVA followed by Tukey's test.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537749&req=5

fig1: Effect of oral 100 mg/kg epicatechin (EC) on circling behavior and striatal dopamine content in MPP+ model. (a) Six days after MPP+-induced damage, the EC effect on apomorphine-induced circling behavior was evaluated. The results are expressed as mean ± S.M.E. of 6–8 animals per group. ∗P < 0.05; data were analyzed by Kruskal-Wallis' test followed by U Mann-Whitney's test. (b) Twenty-four hours after the behavioral test evaluation, dopamine was determined by HPLC coupled to an electrochemical detector. Results are expressed as mean ± S.E.M. of 6–8 animals per group. ∗P < 0.01, two-way ANOVA followed by Tukey's test.
Mentions: The evaluation of the apomorphine-induced behavioral test was carried out 6 days after damage induced by MPP+. In a pilot experiment to select the dose and the time to inject the EC, we observed that a subchronic oral dose of 40, 60, and 80 mg/kg of EC for 5 days was not able to reduce the turning behavior induced by MPP+ (308 ± 28 ipsilateral turns) (data not shown). The subchronic dose of 100 mg/kg for five days reduced the turning behavior after MPP+ to 204.1 ± 20.7, ipsilateral turns/60 min. This effect was not different from a similar, previous dose of EC given 5 h before the MPP+ injury (data not shown). We therefore evaluated the effect of an acute dose of 100 mg/kg of EC administrated 5 h before the damage was induced by MPP+ and then 6 days after the circling behavior was induced by apomorphine. The results indicated that a single acute oral EC dose of 100 mg/kg significantly reduced (P < 0.05) the circling behavior (213.3 ± 24.94, ipsilateral turns/60 min) related to the damage induced by MPP+ (314.4 ± 29.87, ipsilateral turns/60 min). Single EC oral dose administration partially prevented the unbalanced turning behavior in MPP+-treated rats (Figure 1(a)) in the same manner as the chronic oral administration.

Bottom Line: Cu/Zn-dependent superoxide dismutase (Cu/Zn-SOD) activity was significantly (P < 0.05) reduced as a consequence of MPP(+) damage.Such effects persisted in animals injured with MPP(+).The results show that EC is effective against MPP(+)-induced biochemical and behavioral damage, which is possible by an increase in Cu/Zn-SOD activity.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, 14269 Mexico City, Mexico.

ABSTRACT
Parkinson's disease is a neurodegenerative disorder characterized by movement alterations caused by reduced dopaminergic neurotransmission in the nigrostriatal pathway, presumably by oxidative stress (OS). MPP(+) intrastriatal injection leads to the overproduction of free radicals (FR). The increasing formation of FR produces OS, a decline in dopamine (DA) content, and behavioral disorders. Epicatechin (EC) has shown the ability to be FR scavenger, an antioxidant enzyme inductor, a redox state modulator, and transition metal chelator. Acute administration of 100 mg/kg of EC significantly prevented (P < 0.05) the circling MPP(+)-induced behavior (10 μg/8 μL). Likewise, EC significantly (P < 0.05) reduced the formation of fluorescent lipid products caused by MPP(+). MPP(+) injection produced (P < 0.05) increased enzymatic activity of the constitutive nitric oxide synthase (cNOS). This effect was blocked with acute EC pretreatment. Cu/Zn-dependent superoxide dismutase (Cu/Zn-SOD) activity was significantly (P < 0.05) reduced as a consequence of MPP(+) damage. EC produced a slight increase (≈20%) in Cu/Zn-SOD activity in the control group. Such effects persisted in animals injured with MPP(+). The results show that EC is effective against MPP(+)-induced biochemical and behavioral damage, which is possible by an increase in Cu/Zn-SOD activity.

No MeSH data available.


Related in: MedlinePlus