الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
Summary
Tissue drug distribution is nonhomogeneous and the tissue specificity manifested by impaired tissue drug penetration is best exemplified by the nervous, eye, renal and the prostatic tissues. In the meantime, it has been demonstrated that pathological conditions may affect the tissue distribution and kinetics of administered drugs; as they may alter the magnitude and duration of drug content in targeted organs. This has acknowledged the drug-tissue bio-distribution area of research as they pave the way for the proper selection of drug derivative and its dosage. Drug tissue bio-distribution studies in different disease models are also necessary to ensure that the drug targeted organs would not experience a reduced affinity by the tissue pathology.
Nitroimidazole is a parent compound to a number of derivatives which efficiently fight anaerobic bacteria and mono-cellular parasites. Since most the of Nitroimidazole susceptible organisms attack the gastrointestinal tract and cause their inflammation, the main aim of the present study was to evaluate the gastrointestinal tissue (GIT) distribution of 125I-metronidazole (125I–MET) and 125I-2nitroimidazole (125I–NIM) in Escherichia coli-induced gastrointestinal infection in mice. The present study also aimed at exploring the optimum conditions for radiolabelling of both compounds using 125I.
Experimental Design
To study the tissue distribution of 125I-MET and 125I-2-NIM in normal and E.coli infected mice, sixty male albino mice were divided into four main groups; and each were subdivided into 3 sub-groups of five mice. Two main healthy groups were given i.v injection of 200µg of 125I –MET or 2-NIM and the other two groups were given 2 × 108 E. coli organisms suspended in 200 μl saline via oral route for induction of bacterial gastroenteritis 24 hr. before i.v. injection with (125I-2MET or 125I-2NIM).To ensure the reliability of the bio-distribution data, a parallel quality control study has been conducted to guarantee that the injected materials would not disrupt the biological integrity of the experimental animals. Perturbing the body physiology by the administered materials is likely to provide misrepresentative bio-distribution data. The study involved the use of seven more animal groups each of five mice which have treated as follows: one as a control, one infected with E. coli, one injected with125I only, two E .coli non-infected and two E. coli infected groups each injected with either cold metronidazole or 2-nitroimidazole. The overall grouping of the used animals was as follows:
Control groups for all treatments
1- group (A) which received no treatment.
2- group (B) was the normal group, injected with (Iodine-125).
3- group (C) was the infected group.
In case of drug Metronidazole (MET)
4-group (D) was the normal group, injected with MET drug.
5- group (E) was the normal group, injected with labeled 125I-MET complex.
6- group (F) was the infected group, injected with MET drug.
7- group (G) was the infected group, injected with labeled 125I-MET complex.
In case of drug 2-Nitroimidazole (2-NIM)
4-group (D) was the normal group, injected with 2-NIM drug.
5- group (E) was the normal group, injected with labeled 125I-2-NIM complex.
6- group (F) was the infected group, injected with 2-NIM drug.
7- group (G) was the infected, injected with labeled 125I-2-NIM complex.
Data from the present study showed that for radiolabelling of MET, the best yield of the tracer was attained when (200 µg) of the compound was oxidized by (50µg) of the iodogen and adding 10 μL 3.7 MBq Na125I to the reaction that was mediated at pH 7.0, 80C for 20 min. They also showed that the optimum yield of 125I-2NIM was achieved by using (250 µg) of 2-NIM, utilizing (100 µg) CAT as an oxidizing agent and by the addition of 10 μL 3.7 MBq Na125I at pH 7.0, 60C over 20 min.
Data also showed that following I.V injection of both tracers, both 125I-2MET and 125I-2NIM.experienced high blood to tissue perfusion after only 30 min. They also showed that while 125I-2MET continued to leak from the blood to the peripheral tissue over 180 min, 125I-2NIM underwent a reversed tissue to blood mobilization after 60 min. Depsite the biphasic changes in blood 125I-2NIM level , both tracers underwent a comparable average blood concertation. GIT infection enhanced the local GIT perfusion of both medications. Despite the more enhancing effect of infection on the injected 125I-2NIM.2 proportion accumulated in GIT tissue, the GIT uptake of 125I-2MET MET remained to be higher through all intervals in normal and infected mice. Data also demonstrated that more than 60% of injected 125I-2NIM tracers were excreted in urine after 180 min while only 20% of injected 125I-2MET tracer was cleared in urine over the same period. Data also included the measurement of inflammatory markers, hematological parameters, liver functions, protein pattern and lipid profile.
Conclusion
The present study heralds different tissue distribution kinetics between 125I-2MET and 125I-2NIM in normal and E.coli infected albino mice. The parallel average blood level of the same injected dose of 125I-2MET and 125I-2NIM. suggested their quantifiable equality in targeting anaerobic septicemia. Because enteric infection has been found to favor gastrointestinal uptake of more 125I-2MET than 125I-2NIM., MET seems to be a more appropriate candidate in treating gastrointestinal infection caused by Entamoeba histolyticum, Balantidium coli, Giardia lamblia, Heliobacter pylori or Clostridium difficile than 2-NIM. As 125I-2MET achieved higher concentrations in the GIT and more stable concentration in the liver tissues in infected animals in comparison to 125I-2NI, MET appeared to be superior to 2-NIM in the prophylaxis and the treatment of amebic liver hepatitis complicating enteric amebiasis. Finally, the immense excretion of 125I-2NIM in urine makes it more eligible for the treatment of Trichomonas vaginalis infection than MET.