Limits...
Identify Melatonin as a Novel Therapeutic Reagent in the Treatment of 1-Bromopropane(1-BP) Intoxication

View Article: PubMed Central - PubMed

ABSTRACT

1-Bromopropane (1-BP) has been used as an alternative for fluoride compounds and 1-BP intoxication may involve lung, liver, and central neural system (CNS). Our previous studies showed that 1-BP impaired memory ability by compromising antioxidant cellular defenses. Melatonin is a powerful endogenous

antioxidant, and the objective of this study was to explore the therapeutic role of melatonin in the treatment of 1-BP intoxication. Rats were intragastrically treated with 1-BP with or without melatonin, and then sacrificed on 27th day after 1-BP administration. The Morris water maze (MWM) test was used to evaluate the spatial learning and memory ability of the experimental animals, and NeuN staining was performed to assess neuron loss in hippocampus. We found that rats treated with 1-BP spent more time and swam longer distance before landing on the hidden platform with a comparable swimming speed, which was markedly mitigated by the pretreatment with melatonin in a concentration-dependent manner. In addition, 1-BP-induced notable decrease in neuron population in hippocampus by promoting apoptosis, and melatonin pretreatment attenuated those changes in brain. The GSH/GSSG ratio was proportionately decreased and heme oxygenase 1 was increased in the rats exposed to 1-BP (Figure 6), and administration of melatonin restored them. Meanwhile, MDA, the level of lipid peroxidation product, was significantly increased upon exposed to 1-BP, which was significantly attenuated by melatonin pretreatment, indicating that administration of 1-BP could interfere with redox homeostasis of brain in rat, and such 1-BP-induced biomedical changes were reversed by treatment with melatonin.

We conclude that treatment with melatonin attenuates 1-BP-induced CNS toxicity through its ROS scavenging effect.

No MeSH data available.


Related in: MedlinePlus

Memory impairment was significantly positively correlated with the GSH/GSSG ratio reduction in hippocampus. The GSH/GSSG ratio of hippocampus displayed significantly negative correlations with the escape latency (A) and the swimming distance (B), and positive correlation with the number across the platform (C) and the percentage of time in target quadrant (D). Correlation analysis was determined by the Spearman correlation coefficient.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4998236&req=5

Figure 4: Memory impairment was significantly positively correlated with the GSH/GSSG ratio reduction in hippocampus. The GSH/GSSG ratio of hippocampus displayed significantly negative correlations with the escape latency (A) and the swimming distance (B), and positive correlation with the number across the platform (C) and the percentage of time in target quadrant (D). Correlation analysis was determined by the Spearman correlation coefficient.

Mentions: 4. The GSH/GSSG ratio reduction in hippocampus was significantly positively correlated with impairment of memory ability and spatial learning. To further identify the molecular mechanism of the impairment of memory ability and spatial learning, we determined the brain redox status by measuring several important indexes about oxidative stress in hippocampus, and correlations of cognitive performances in the MWM test with the GSH/GSSG ratio of hippocampus were assessed. As shown in Figure 4, the GSH/GSSG ratio of hippocampus was significantly negatively correlated with escape latency and distance traveled, and positively with percentage of time spent in target quadrant and number of platform crossing. Furthermore, another important oxidative radical, MDA, were determined in all experimental animals and its correlation with cognitive performances in the MWM test was also evaluated. As shown in Figure 5, MDA content of hippocampus was significantly positively correlated with escape latency and distance traveled, and negatively with percentage of time spent in target quadrant and number of platform crossing, indicating that there was positive correlation between redox status and cognitive deficits induced by 1-BP.


Identify Melatonin as a Novel Therapeutic Reagent in the Treatment of 1-Bromopropane(1-BP) Intoxication
Memory impairment was significantly positively correlated with the GSH/GSSG ratio reduction in hippocampus. The GSH/GSSG ratio of hippocampus displayed significantly negative correlations with the escape latency (A) and the swimming distance (B), and positive correlation with the number across the platform (C) and the percentage of time in target quadrant (D). Correlation analysis was determined by the Spearman correlation coefficient.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998236&req=5

Figure 4: Memory impairment was significantly positively correlated with the GSH/GSSG ratio reduction in hippocampus. The GSH/GSSG ratio of hippocampus displayed significantly negative correlations with the escape latency (A) and the swimming distance (B), and positive correlation with the number across the platform (C) and the percentage of time in target quadrant (D). Correlation analysis was determined by the Spearman correlation coefficient.
Mentions: 4. The GSH/GSSG ratio reduction in hippocampus was significantly positively correlated with impairment of memory ability and spatial learning. To further identify the molecular mechanism of the impairment of memory ability and spatial learning, we determined the brain redox status by measuring several important indexes about oxidative stress in hippocampus, and correlations of cognitive performances in the MWM test with the GSH/GSSG ratio of hippocampus were assessed. As shown in Figure 4, the GSH/GSSG ratio of hippocampus was significantly negatively correlated with escape latency and distance traveled, and positively with percentage of time spent in target quadrant and number of platform crossing. Furthermore, another important oxidative radical, MDA, were determined in all experimental animals and its correlation with cognitive performances in the MWM test was also evaluated. As shown in Figure 5, MDA content of hippocampus was significantly positively correlated with escape latency and distance traveled, and negatively with percentage of time spent in target quadrant and number of platform crossing, indicating that there was positive correlation between redox status and cognitive deficits induced by 1-BP.

View Article: PubMed Central - PubMed

ABSTRACT

1-Bromopropane (1-BP) has been used as an alternative for fluoride compounds and 1-BP intoxication may involve lung, liver, and central neural system (CNS). Our previous studies showed that 1-BP impaired memory ability by compromising antioxidant cellular defenses. Melatonin is a powerful endogenous

antioxidant, and the objective of this study was to explore the therapeutic role of melatonin in the treatment of 1-BP intoxication. Rats were intragastrically treated with 1-BP with or without melatonin, and then sacrificed on 27th day after 1-BP administration. The Morris water maze (MWM) test was used to evaluate the spatial learning and memory ability of the experimental animals, and NeuN staining was performed to assess neuron loss in hippocampus. We found that rats treated with 1-BP spent more time and swam longer distance before landing on the hidden platform with a comparable swimming speed, which was markedly mitigated by the pretreatment with melatonin in a concentration-dependent manner. In addition, 1-BP-induced notable decrease in neuron population in hippocampus by promoting apoptosis, and melatonin pretreatment attenuated those changes in brain. The GSH/GSSG ratio was proportionately decreased and heme oxygenase 1 was increased in the rats exposed to 1-BP (Figure 6), and administration of melatonin restored them. Meanwhile, MDA, the level of lipid peroxidation product, was significantly increased upon exposed to 1-BP, which was significantly attenuated by melatonin pretreatment, indicating that administration of 1-BP could interfere with redox homeostasis of brain in rat, and such 1-BP-induced biomedical changes were reversed by treatment with melatonin.

We conclude that treatment with melatonin attenuates 1-BP-induced CNS toxicity through its ROS scavenging effect.

No MeSH data available.


Related in: MedlinePlus