التأثير الوقائي لحمض الفوليك عن الضرر الناجم عن الحمل الزائد للميثيونين على المعايير الفسلجية والنسجية والجزيئية في ذكور الفئران

The preventive effect of folic acid on the damage induced by methionine overload on physiology , histology and molecular aspect in male mice

This study is carried out to investigate the protective role of folic acid on the
hepatic and kidney damage induced by methionine overload in male mice .
One hundred fifty (150) mice were divided into five groups (30/group),the
first group was intubated with tap water for six weeks and served as control
group(G1),mice in the second group were intubated orally with 100 mg/kg B .W
of methionine (G2).While animals of the third group were intubated with 0.07
mg/kg B.W of folic acid (G3), micein the fourth group (G4) were intubated
orally with 0.07 mg/kg B.W of folic acidin addition to methionine,animals of
the last group (G5) were intubated with 100 mg\Kg B.W. iron .
Fasting blood samples were collected by cardiac punctures technique at six
weeks of experimental for measuring :A-biomarker of oxidative stress including
serum Glutathione (GSH)and Malondialdehyde (MDA) concentrations. B-
serum Alanine Aminotransferase (ALT) , Aspartate Amino transferase (AST)
and Alkaline phosphatase (ALP) activities , albumin and globulin
concentrations.C -serum Iron ,Ferritin and transferrin concentrationand level
of the hormone hepcidin, furthermore kidney and hepatic tissue were assessed
for histopathological changes , andasample of the liver was taken to measure
gene expression, the results revealed to a significant (p<0.01) increase in MDA
concentration in G2 and G5Compareto control and folic acid treated groupsand
a significant decrease (p<0.01) in G3 and G4 ,presentasignificant decrease
(p<0.01) in serum GSH in G2,G5.Asignificant (p<0.01) increasein serum
GSHin G3 and G4 .And a significant decrease (p<0.01) inalbumin , globulin
concentrationsin G2 and G5, also showed a significant (p<0.01) increase in
ALT, AST and ALP activitiesin G2, G5 anda significant decrease (p<0.01) in
G3 ,appeara significant increase (P<0.01) in serum Iron ,Ferritinand
Transferrin in G2,G5 and appeara significant increase (P<0.01) in level hepcidin
hormoneand bilirubin concentration in(G2,G5), our result appeara significant decrease (p<0.01) in RBC , Hb and PCVin G2and G5Compareto control.In our study was found the most common gene expression(HAMP)in the group
with iron overload G5 rather than other groups .The present study finds decrease
of gene expression in the methionine group G2 and folic acid group G3
Compare to the control group.The results of the current study showed intubating
mice with methionine and folic acid G4 for six weeks no difference in gene
expression compare to the control group, the results shows that there isa damage
effect on liver and kidney tissue in groups exposed to methionineshowed
dilatation in central vein and dilatation in sinusoid aggregations inflammatory
cells, degeneration in tunica intima of central vein and hyperplasia Kupffer cells
degeneration and hypertrophy in hepatocytes, disappearance of arrangement of
the hepatic cords and infiltration of mononuclear inflammatory cells in the portal
and pyknotic nucleus in hepatocytes, also showeddemonstrated glomerular
atrophy, enlargement of the urinary space, distal tubules atrophy,the change in
the shape of the cells lining the tubules where their normal shape is cuboid, but in
the case of methionine overload the shape became flat,as for the proximal
tubules, there is no noticeable change, but note that the color of the cytoplasm
has become blue, evidence of damage to the kidney tissue.As it has become
basal,Hyaline cast accumulation ,and the presence of congestion in the artery and
the collection of mononuclear inflammatory cells and hypertrophy of the tunica
intima, sections in the liver of animal treated with (methionine and folic acid)
showed infiltration of mononuclear inflammatory cells in per portal area but less
than the liver in the case of methionine ,decreased hepatocyte ,Kupffer cell
degeneration.It was observed that the kidney tissues returned to normal and the
kidney healing was observed, as mononuclear inflammatory cells invaded and
glomerular atrophy was observed, but at a lesser rate than the atrophy case in the
methionine group only and the cytoplasm of cells in the proximal tube is pink
(acidic) Closer to natural,in the case of 0.07mg/kg B.W.of folic acid showed
not accumulation of Hyaline cast Compared with the kidney of animal treated
with 100mg/kg B.W methionine . In conclusion, the results of this study confirm the protective role of folic acid
against deleterious effect of liver and kidney caused by methionine overload in
male mice.