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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.


Effects of melatonin on 1-bromopropane (1-BP) induced hippocampal histopathological changes (Neun staining, A: control group, B: 1-BP-treated group; C: 1-BP and melatonin-treated group). Effects of melatonin on 1-bromopropane (1-BP) induced neuron apoptosis in hippocampal (TUNEL assay, A: control group, B: 1-BP-treated group; C: 1-BP and 10 mg/kg BW melatonin-treated group). 1-BP = 1-bromopropane.
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Figure 3: Effects of melatonin on 1-bromopropane (1-BP) induced hippocampal histopathological changes (Neun staining, A: control group, B: 1-BP-treated group; C: 1-BP and melatonin-treated group). Effects of melatonin on 1-bromopropane (1-BP) induced neuron apoptosis in hippocampal (TUNEL assay, A: control group, B: 1-BP-treated group; C: 1-BP and 10 mg/kg BW melatonin-treated group). 1-BP = 1-bromopropane.

Mentions: 3. Treatment with melatonin restored neuron loss in brains of SD rats exposed to 1-BP Hippocampus has an important role in cognitive function. Therefore, the numbers of neurons in this part were estimated to evaluate the effect of 1-BP on the survival of neurons in Hippocampus. It has been reported that the impairment of memory ability and spatial learning could be resulted from loss of neuron,27 we next examined the status of neuron loss in each group. The brains were harvested, sectioned, and stained with Neun to count the neurons in each group. As indicated in Figure 3 1-BP induced notable decrease in neuron population in hippocampus, and such neuron loss was immunohistochemistry visualized in Figure 3, and melatonin pretreatment attenuated those changes in brain (Figure 3). In addition, we determined the apoptosis status of each above group and found that 1-BP induced increase in apoptosis of neurons in hippocampus, and induced apoptosis was evidently attenuated by melatonin treatment (Figure 3).


Identify Melatonin as a Novel Therapeutic Reagent in the Treatment of 1-Bromopropane(1-BP) Intoxication
Effects of melatonin on 1-bromopropane (1-BP) induced hippocampal histopathological changes (Neun staining, A: control group, B: 1-BP-treated group; C: 1-BP and melatonin-treated group). Effects of melatonin on 1-bromopropane (1-BP) induced neuron apoptosis in hippocampal (TUNEL assay, A: control group, B: 1-BP-treated group; C: 1-BP and 10 mg/kg BW melatonin-treated group). 1-BP = 1-bromopropane.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Effects of melatonin on 1-bromopropane (1-BP) induced hippocampal histopathological changes (Neun staining, A: control group, B: 1-BP-treated group; C: 1-BP and melatonin-treated group). Effects of melatonin on 1-bromopropane (1-BP) induced neuron apoptosis in hippocampal (TUNEL assay, A: control group, B: 1-BP-treated group; C: 1-BP and 10 mg/kg BW melatonin-treated group). 1-BP = 1-bromopropane.
Mentions: 3. Treatment with melatonin restored neuron loss in brains of SD rats exposed to 1-BP Hippocampus has an important role in cognitive function. Therefore, the numbers of neurons in this part were estimated to evaluate the effect of 1-BP on the survival of neurons in Hippocampus. It has been reported that the impairment of memory ability and spatial learning could be resulted from loss of neuron,27 we next examined the status of neuron loss in each group. The brains were harvested, sectioned, and stained with Neun to count the neurons in each group. As indicated in Figure 3 1-BP induced notable decrease in neuron population in hippocampus, and such neuron loss was immunohistochemistry visualized in Figure 3, and melatonin pretreatment attenuated those changes in brain (Figure 3). In addition, we determined the apoptosis status of each above group and found that 1-BP induced increase in apoptosis of neurons in hippocampus, and induced apoptosis was evidently attenuated by melatonin treatment (Figure 3).

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.