تأثير فرط الهيموسستين في الدم على بعض الدلائل الحيوية ونشاط ناقضات العظم في ذكور الأرانب المستحدث بالمثيونين

The Effect of Hyperhomocysteinemia on Some Biomarkers and Osteoclasts Activityin Male Rabbits Induced by Methionine

This study was carries out to investigate the effect of Hyperhomocysteinemia (HHcy)
on osteoclast activity that induced by methionine overload in male rabbits.
Twenty adult male rabbits were used, which were randomly divided into two
groups (10/group). The first group was intubated with tap water and serve as control
group. Rabbits in the second group were intubated orally with (100mg/kg BW) of
methionine daily for 12 weeks.
Fasting blood samples were collected by heart puncture technique after 12 weeks of
experiment to measure of the following criteria: a- Homocysteine (Hcy) concentration
in serum. b- Biomarker of osteoclast activity including: Receptor Activator of Nuclear
factor Kappa-b (RANK) and Receptor Activator of Nuclear factor Kappa-b Ligand
(RANK-L). c- Measuring the level of ions and minerals including: calcium (Ca+2),
sodium (Na+
), potassium (K+
) and iron (Fe+2) concentration in serum. d- Parathyroid
hormone (PTH) concentration in serum. e- Alkaline phosphatase (ALP) enzyme. f-
Biomarker of oxidative stress including: serum glutathione (GSH) and malondialdehyde
(MDA) concentrations, in addition to studying histopathological changes of the femur
bone.
The results of this study show that daily oral intubation of methionine (100mg/kg
BW) to males rabbits for 12 weeks cause significant increase (p≤0.001) in the
concentration of Hcy, RANK, RANK-L, PTH, ALP, Fe+2 and MDA, and significant
decrease (p≤0.001) in serum Ca+2, Na+
and GSH concentration, in addition to
significant decrease (p≤0.05) in serum K+
concentration, when compared to the control
group. The histological examination by lighting microscope and scanning electronic
microscope showed that daily oral intubation of methionine caused increase in the
numbers and activity of osteoclast cells accompanied by erosion and necrosis of the
trabecular structure of the femur bone.
As for correlations there are a significant (p≤0.01) positive correlation between Hcy
and all of RANK-L, Fe+2 and ALP. The Hcy also show significant (p≤0.01) negative
correlation with Ca+2 and GSH. RANK-L showed a significant (p≤0.01) positive
correlation with RANK. PTH showed significant positive (p≤0.01) correlation with
RANK-L, while it showed significant (p≤0.01) negative correlation with Ca+2
.In summary, it is concluded from the current study that HHcy that induced by
excess l-methionine intubation caused a significant increased in the levels of RANK and
RANK-L, which has resulted in an increase in the numbers and activity of osteoclasts
resulting in necrosis and erosion in the trabecular structure of the femur bone. This
shows that high Hcy in the blood is a risk factor for the occurrence of osteoporosis.