4 research outputs found
Maternal exposure to the environmental pollutant "BDE-47" impairs the postnatal development of rat cerebellar cortex by modulating neuronal proliferation, synaptogenesis, NGF and BDNF pathways
. 2,2’,4,4’-Tetrabromodiphenyl ether (BDE47) is an environmental contaminant that crosses the
blood placental barrier and interferes with the
homeostasis of fetal thyroid hormones.
Aim of work. This study was designed to investigate
the perinatal effect of BDE-47 exposure on the postnatal
development of the rat cerebellar cortex.
Materials and methods. This study was carried out
on 20 pregnant rats and 36 of their offspring. The
pregnant rats were divided equally into control and
BDE-47 treated mother groups; supplemented orally
with BDE-47 (0.2 mg/kg/day from day 8 of gestation
until the day of weaning). The offspring of both mother
groups were subdivided, according to their
developmental age, into three subgroups; PND14,
PND21and PND42. SerumT3, T4 and TSH were
assessed for dams and their offspring. Testing the motor
coordination of the offspring via the rotarod test was
conducted. Sections of the cerebellar cortex from
offspring subgroups were stained with hematoxylin and
eosin alongside immunohistochemical reactions and
optical density of nerve growth factor (NGF), brain
derived neurotrophic factor (BDNF), proliferating cell
nuclear antigen (PCNA) and synaptophysin (SYN) were
assessed. Also, the thickness of different layers of the
cerebellar cortex was histomorphometrically measured.
Results. BDE-47 treated mothers and their offspring
subgroups showed a significant decrease in the serum
free T3, T4 and increased TSH. The BDE-47 offspring
displayed incoordination of the motor activity together
with disturbed cytoarchitecture of the cerebellar cortical
layers, and impaired migration of its germinative
neuronal zones, particularly on PND14 and PND21.
Moreover, these offspring displayed a decrease of the
immune-expression and optical density of NGF, BDNF
in the cerebellar cortical layers with impaired
proliferation, and synaptogenesis.
Conclusion. Maternal exposure to BDE-47 during
pregnancy and lactation effectuated a potential
deleterious retarding effect on the postnatal development
of the rat cerebellar cortex mostly via modulating
neuronal proliferation, synaptogenesis, NGF and BDNF
pathways secondary to its hypothyroid effect
Mexican tea (Dysphania ambrosioides (L.) Mosyakin & Clemants) seeds attenuate tourniquet-induced hind limb ischemia–reperfusion injury by modulating ROS and NLRP3 inflammasome pathways
The main pathophysiological mechanisms of hind limb ischemia–reperfusion injury (HLIRI) are increased oxidative stress and inflammation. The present study was designed to characterize the phytocontents of Dysphania ambrosioides (DA) seeds extract via LC-MS/MS and investigate its effect on left hindlimb IR injury and the underlying mechanisms. Thirty adult rats (n = 6 per group) were divided into five groups: Control group; HLIRI group, HLIRI + DA (100 mg/kg) group, HLIRI + DA (200 mg/kg) group, and HLIRI + cilostazol (30 mg/kg) group. HE staining’s of the left gastrocnemius muscle and left kidney was done. Renal function, and both total and muscle creatine kinases were measured in serum. Oxidative stress markers (MDA, SOD, Nrf2 and HO-1), inflammatory markers (NLRP3, IL-1β and TNF-α) and caspase-3 as an apoptotic marker were measured in left gastrocnemius muscle. We found that DA extract contains 60 metabolites and its pretreatment prevented left kidney and left gastrocnemius muscle damage and decreased oxidative stress markers, inflammatory markers, and caspase-3 levels, compared to the control group. Moreover, the effect of the extract was dose-dependent and better than that of the reference drug, cilostazol. This study suggested that D. ambrosioides seeds have a protective effect on HLIRI, which may be related to the antioxidant, anti-inflammatory and antiapoptotic mechanisms