الفهرس 
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Abstract
BPA is considered as a solitary of the furthermost popular worldwide chemicals as an estrogenic endocrine disrupting substance involved in the industry of polycarbonate plastics, medical devices, pharmaceuticals, and others. Divergent tissues and organs are affected by the toxic effects of BPA comprising liver, respiratory system, kidney, mucous membranes, immune system and the skin. BPA is generally metabolized by the liver so exposed it to toxic activities through induction of OS.
Curcumin has possible curative actions on varied poisonous effects, exerted on different diseases as cardiovascular and neurodegenerative along with antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers.
The current study aimed to investigate the toxicity of BPA on liver tissue of male mice and insight the role of curcumin as an antioxidant supplement through the following parameters: histopathological and immunohistochemical studies along with flow cytometric analysis. Fifty mice were haphazardly divided into 5 groups; each of 10 mice. group I: normal mice were received a freely well-balanced diet and water. group II: mice were administered corn oil. group III: mice were received curcumin (80 mg/kg b.w). group IV: mice were administered BPA (50 mg/ Kg b.w). group V: mice were received curcumin (80 mg/kg b.w), complemented with BPA (50 mg / Kg b.w) one hour after curcumin.
Curcumin or BPA were dissolved in corn oil and administered orally by gastric tube 5 times per week for 4 weeks. Mice were weighed and sacrificed post 2 and 4 weeks from the commencement of the experiment. Liver was excised out, weighed and either fixed in 10% neutral buffered formalin and prepared for histopathological and immunohistochemical analyses or used as fresh samples for flow cytometric analysis.
The results of the current study are summarized as the following:
Body weight:
Higher significant difference in mean body weight after 2 weeks was seen in bisphenol group with 16.23 % of change compared with normal group. Mean body weight after 4 weeks showed no significant differences in bisphenol group and in curcumin plus bisphenol group comparing with normal group with 1.35 % and 10.31 % of changes respectively.
Histopathological findings:
Liver sections of mice from normal group stained with H&E revealed normal histological architecture with hepatocytes and patent sinusoids. Bisphenol administration after 2 weeks displayed liver injury as vacuolar degenerative, macrosteatosis and giant nuclei in some hepatocytes. Cellular inflammatory infiltration surrounding congested portal vein and necrosis in some hepatocytes were seen after 4 weeks. In curcumin plus bisphenol group after 2 or 4 weeks, improvement in liver tissue by way of diminution in inflammation and reduction in blood vessels congestion in addition to tiny cells exhibited pyknotic nuclei.
Regenerated hepatocytes which indicated histological features relatively similar to normal group especially after 4 weeks.
Immunohistochemical findings of apoptosis-inducing factor (AIF)
Strong cytoplasmic positivity of AIF in hepatocytes especially around central vein was observed in normal sections. Moderate cytoplasmic AIF immunostaining reaction in hepatocytes from either vehicle group or curcumin group after 2 and 4 weeks. In bisphenol group either 2 or 4 weeks hepatocytes exhibited nuclear immunostaining intensity of AIF ranged from moderate to strong activity. Curcumin plus bisphenol group for 2 weeks displayed weak to moderate cytoplasmic reaction in little hepatocytes near central vein. Four weeks after administration of curcumin and bisphenol, strong cytoplasmic immunoreaction was observed in many hepatocytes of centrilobular area relatively as exhibited in normal liver sections.
Image analysis of AIF
AIF immunostaining expression in liver sections from all studied groups were evaluated by measuring area with immunoreaction positivity expressed in area percentage. Attained results of area % were confirmed the findings of immunoreaction positivity. There were higher significant difference in area % in bisphenol group after 2 weeks comparing with curcumin group and curcumin plus bisphenol group. Area % in bisphenol group exhibited higher significant difference after 4 weeks compared with normal group while curcumin plus bisphenol group demonstrated lower significant difference in comparison with normal and bisphenol groups.
Flow cytometric analysis
The cell cycle data after 2 weeks of experiment showed higher significant difference in SubG1 in curcumin plus bisphenol group in comparison with other groups. Lower significant differences in G0/G1 in bisphenol and curcumin plus bisphenol groups comparing with normal and higher significant differences in comparison with curcumin group. Bisphenol group showed higher significant alteration in S-phase as compared with, vehicle and curcumin groups. Curcumin plus bisphenol group has lower significant difference in S- phase comparing with vehicle and bisphenol groups. G2/M phase exhibited lower significant dissimilar in curcumin plus bisphenol group in comparison with other experimental groups.
The cell cycle data after 4 weeks exhibited higher significant difference in SubG1 in curcumin plus bisphenol group compared with other groups. Lower significant alteration in G0/G1 was seen in curcumin plus bisphenol group in comparison with normal and bisphenol groups. In addition to lower significant difference in S-phase of curcumin plus bisphenol group as compared with vehicle and curcumin groups. G2/M phase in curcumin plus bisphenol group displayed lesser significant difference when compared with vehicle, curcumin and bisphenol groups.