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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) influenced SD rats of spatial memory ability in Morris Water Maze (MWM). Data were shown as mean ± SEM (n = 12). (A) The number across the platform in SD rats. (B) The percentage of time in target quadrant in SD rats. (C) The swimming speed of SD rats. ∗P < 0.05, ∗∗P < 0.01, nsP > 0.05 versus 1-BP group; ##P < 0.01 versus control group. 1-BP = 1-bromopropane, MWM = Morris Water Maze, SD rats = Sprague-Dawley rats.
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Figure 2: Effects of melatonin on 1-bromopropane (1-BP) influenced SD rats of spatial memory ability in Morris Water Maze (MWM). Data were shown as mean ± SEM (n = 12). (A) The number across the platform in SD rats. (B) The percentage of time in target quadrant in SD rats. (C) The swimming speed of SD rats. ∗P < 0.05, ∗∗P < 0.01, nsP > 0.05 versus 1-BP group; ##P < 0.01 versus control group. 1-BP = 1-bromopropane, MWM = Morris Water Maze, SD rats = Sprague-Dawley rats.

Mentions: Previous in vivo and in vitro experiments showed that administration of 1-BP evidently impaired spatial learning and memory abilities of rats.26 In this study, a MWM test was used to verify the successful establishment of animal model for 1-BP intoxication. Prior to the MWM test, all rats in each group could successfully swim to the platform, and the escape latency time, swimming distance, and swimming speed were measured to evaluate memory impair and spatial learning deficits in the following hidden platform test. Compared with the animals in the control group, SD rats treated with 1-BP spent more time (Figure 1A) and swam longer distance (Figure 1B) before landing on the hidden platform with a comparable swimming speed (Figure 1C), which was markedly mitigated by the pretreatment with melatonin in a concentration-dependent manner (Figure 1). To verify the therapeutic effect of melatonin in the treatment of 1-BP intoxication, 5 different dose of melatonin was intravenously given as described in methods section, and we found that treatment of melatonin significantly ameliorated 1-BP caused impairment of memory ability and spatial learning, as evidenced by its ability to reduce the time and distance for rats to find the hidden platform compared with those exposed to 1-BP in a concentration-dependent manner (Figure 1). Furthermore, the results of the probe test demonstrated that exposure to 1-BP caused the impairment of spatial memory, and all rats treated with 1-BP exhibited significantly reduced number of times they cross the former target platform area, compared with the control group (Figure 2), which was markedly mitigated by the treatment with melatonin in a concentration-dependent manner (Figure 2).


Identify Melatonin as a Novel Therapeutic Reagent in the Treatment of 1-Bromopropane(1-BP) Intoxication
Effects of melatonin on 1-bromopropane (1-BP) influenced SD rats of spatial memory ability in Morris Water Maze (MWM). Data were shown as mean ± SEM (n = 12). (A) The number across the platform in SD rats. (B) The percentage of time in target quadrant in SD rats. (C) The swimming speed of SD rats. ∗P < 0.05, ∗∗P < 0.01, nsP > 0.05 versus 1-BP group; ##P < 0.01 versus control group. 1-BP = 1-bromopropane, MWM = Morris Water Maze, SD rats = Sprague-Dawley rats.
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Figure 2: Effects of melatonin on 1-bromopropane (1-BP) influenced SD rats of spatial memory ability in Morris Water Maze (MWM). Data were shown as mean ± SEM (n = 12). (A) The number across the platform in SD rats. (B) The percentage of time in target quadrant in SD rats. (C) The swimming speed of SD rats. ∗P < 0.05, ∗∗P < 0.01, nsP > 0.05 versus 1-BP group; ##P < 0.01 versus control group. 1-BP = 1-bromopropane, MWM = Morris Water Maze, SD rats = Sprague-Dawley rats.
Mentions: Previous in vivo and in vitro experiments showed that administration of 1-BP evidently impaired spatial learning and memory abilities of rats.26 In this study, a MWM test was used to verify the successful establishment of animal model for 1-BP intoxication. Prior to the MWM test, all rats in each group could successfully swim to the platform, and the escape latency time, swimming distance, and swimming speed were measured to evaluate memory impair and spatial learning deficits in the following hidden platform test. Compared with the animals in the control group, SD rats treated with 1-BP spent more time (Figure 1A) and swam longer distance (Figure 1B) before landing on the hidden platform with a comparable swimming speed (Figure 1C), which was markedly mitigated by the pretreatment with melatonin in a concentration-dependent manner (Figure 1). To verify the therapeutic effect of melatonin in the treatment of 1-BP intoxication, 5 different dose of melatonin was intravenously given as described in methods section, and we found that treatment of melatonin significantly ameliorated 1-BP caused impairment of memory ability and spatial learning, as evidenced by its ability to reduce the time and distance for rats to find the hidden platform compared with those exposed to 1-BP in a concentration-dependent manner (Figure 1). Furthermore, the results of the probe test demonstrated that exposure to 1-BP caused the impairment of spatial memory, and all rats treated with 1-BP exhibited significantly reduced number of times they cross the former target platform area, compared with the control group (Figure 2), which was markedly mitigated by the treatment with melatonin in a concentration-dependent manner (Figure 2).

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.