الفهرس 
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Abstract
The possible modulatory effect of a protective agent against methyl mercury induced developmental
neurotoxicity in rats.
The present study aims to examine the potential role of methylmercury (MMC) in inducing embryotoxicity including developmental neurotoxicity as well as to evaluate the role of naringenin in preventing or alleviating the induced defects.
Pregnant rats were divided into two main groups: The first main group (fetuses group), consisted of four groups each comprising 10 rats. Control group, naringenin group received 50 mg of naringenin /kg b.wt./day, MMC group (1 mg of MMC/ kg b.wt./day), and MMC+ naringenin group received both MMC and naringenin in the same dosage. All groups were treated daily through gastric intubation from 7th to 19th day of gestation. In the second main group (pups group), pregnant rats were divided and received the treatments by the same manner and dosage as the first main group, but the treatment period was extended daily from the 7th day of gestation till postnatal day (PND) 29.
The results of the first main group indicated that oral administration of naringenin to the rats treated with MMC improved the reduction of maternal and fetal body weight and markedly reduced the fetal morphological and skeletal abnormalities. Also, co-treatment with naringenin reduced the cerebral oxidative stress in fetuses (indicated by reduction in Malondialdehyde (MDA) and Nitric Oxide (NO) levels and improvement in total antioxidant activity (TAA)), alleviated the increase in cerebral DNA fragmentation and improved the histpathological lesions observed in cortex of the fetuses.
On the other hand, oral administration of naringenin to the rats treated with MMC at the second main group showed improvement in the abnormalities in neurobehavioral tests (Morris test and the open field test) in both male and female pups. Additionally, treatment with naringenin produced a significant improvement in the levels of monoamines (norepinephrine, dopamine and serotonin) in frontal cortex, hippocampus and mid brain and reduction in the levels of amino acids (aspartate, glutamate, and GABA) in frontal cortex of both sex. Also, co- administration of naringenin with MMC reduced the levels of MDA, NO, calcium, and percentage of fragmented DNA and reversed the reduction in TAA, Na+/K+ ATPase and acetyl cholinesterase in cortex and brain stem areas in both male and female pups. Moreover, naringenin exhibited moderate improvement in the histological changes observed in the cortical region of pups.
Therefore, it can be concluded that exposure to MMC (1 mg / kg b.wt./day) during gestation and lactation had an impact on brain development in fetuses and neonates. It can induce oxidative stress, DNA fragmentation and alterations in the steady-state concentrations of some neurotransmitters. Also, it can interfere with the activities of some neuronal enzymes and induced histological changes in the cortex. These defects lead to postnatal neurobehavioral disturbances (hyperactivity and decrease in learning and memory retention). Co- treatment with naringenin can diminish the neurotoxicity caused by MMC. It can be suggested that naringenin has a neuroprotective effect due to antioxidant and free radical scavenging activity.