288
of mesenchymal stem cells into adipocytes is regulated by PPARɤ. In vitro study has
shown that when cell lines of mouse embryo exposed to tributyltin, it caused the
decrease in DNA methylation in promoter region by increasing the differentiation
into adipocytes [113]. A decreased methylation of 3CpG sites causes the alternation
in expression of PPARɤ2 [113]. In vivo study also has shown the lipid accumulation
in adipocytes will increase the expression of adipogenesis markers PPARɤ and
FABP4, when adipose-derived stem cells (ADSCs) obtained from white adipose
tissue of C57BL/6J mice were exposed to tributyltin [114]. These results showed
that adult parents, (f1) generation with increased adipocyte activity will born F2
offspring having the same size of adipocytes having high expression of PPARɤ,
COX2, and CEBPα [115]. Same alternation was also observed in F3 generation
with many other pathologies. This study also revealed that male obesity is transmitted by female germline and vice versa [115].
Effect on Oxidative Stress
ROS are known to have destructive nature that have lethal pathophysiological
effects on organs since the last 30 years. Free radicals have atoms with one or more
unpaired electrons that induced oxidative stress resulting in lipid peroxidation and
also effect body’s antioxidant defense system (Table 17.3). It is clear evidence that
oxidative stress can cause various diseases like Alzheimer’s Disease, Parkinson’s
Disease, cataracts, atherosclerosis, neoplastic diseases, diabetes, chronic inflammatory [116].
Pesticides as MDCs are toxic chemicals that target biological system due to their
adverse toxic potential. Oxidative stress produced by pesticide remained a toxicological research topic for the last many decades. A number of research projects have
been conducted to determine the toxic effect of these deleterious agents. It is necessary to understand the production of free radicals before studying the adverse effects
of oxidative stress [175]. Numerous biological responses are initiated by oxidative
stress created by these pesticides. In vivo and in vitro study reported the role of
selected pesticides in creating oxidative stress. Oxidative stress caused by ROS also
induced death receptor pathways such as tumor necrosis factor receptor (TNFR)
followed by activation of tumor necrosis factor alpha (TNF-α). After the ligation
process that leads to activation of caspase-8 which then cleaves effector caspase-3.
The high number of TNF-α leads to productions of reactive oxygen species as seen
in rats when exposed with permethrin [76]. Nurr1 which is a transcription factor of
family NR4A proteins plays a significant role in the metabolism of dopaminergic
neurons by inhibiting activity of the transcription factor NF-κB in the brain tissue
[60]. ROS creates oxidative stress that causes lipid peroxidation which then effect
the activity of Nurr1 followed by the induction of NF-κB. At the same time exposure
of permethrin increased the expression of proinflammatory NF-κB transcription
factor by accumulating Nurr1 gene in experimental animal models [117].
S. Kamal et al.
of mesenchymal stem cells into adipocytes is regulated by PPARɤ. In vitro study has
shown that when cell lines of mouse embryo exposed to tributyltin, it caused the
decrease in DNA methylation in promoter region by increasing the differentiation
into adipocytes [113]. A decreased methylation of 3CpG sites causes the alternation
in expression of PPARɤ2 [113]. In vivo study also has shown the lipid accumulation
in adipocytes will increase the expression of adipogenesis markers PPARɤ and
FABP4, when adipose-derived stem cells (ADSCs) obtained from white adipose
tissue of C57BL/6J mice were exposed to tributyltin [114]. These results showed
that adult parents, (f1) generation with increased adipocyte activity will born F2
offspring having the same size of adipocytes having high expression of PPARɤ,
COX2, and CEBPα [115]. Same alternation was also observed in F3 generation
with many other pathologies. This study also revealed that male obesity is transmitted by female germline and vice versa [115].
Effect on Oxidative Stress
ROS are known to have destructive nature that have lethal pathophysiological
effects on organs since the last 30 years. Free radicals have atoms with one or more
unpaired electrons that induced oxidative stress resulting in lipid peroxidation and
also effect body’s antioxidant defense system (Table 17.3). It is clear evidence that
oxidative stress can cause various diseases like Alzheimer’s Disease, Parkinson’s
Disease, cataracts, atherosclerosis, neoplastic diseases, diabetes, chronic inflammatory [116].
Pesticides as MDCs are toxic chemicals that target biological system due to their
adverse toxic potential. Oxidative stress produced by pesticide remained a toxicological research topic for the last many decades. A number of research projects have
been conducted to determine the toxic effect of these deleterious agents. It is necessary to understand the production of free radicals before studying the adverse effects
of oxidative stress [175]. Numerous biological responses are initiated by oxidative
stress created by these pesticides. In vivo and in vitro study reported the role of
selected pesticides in creating oxidative stress. Oxidative stress caused by ROS also
induced death receptor pathways such as tumor necrosis factor receptor (TNFR)
followed by activation of tumor necrosis factor alpha (TNF-α). After the ligation
process that leads to activation of caspase-8 which then cleaves effector caspase-3.
The high number of TNF-α leads to productions of reactive oxygen species as seen
in rats when exposed with permethrin [76]. Nurr1 which is a transcription factor of
family NR4A proteins plays a significant role in the metabolism of dopaminergic
neurons by inhibiting activity of the transcription factor NF-κB in the brain tissue
[60]. ROS creates oxidative stress that causes lipid peroxidation which then effect
the activity of Nurr1 followed by the induction of NF-κB. At the same time exposure
of permethrin increased the expression of proinflammatory NF-κB transcription
factor by accumulating Nurr1 gene in experimental animal models [117].
S. Kamal et al.