Radioiodination of Certain Antibacterial Drugs and Detection of Some Physiological Effects in Male Mice

Abstract

Specific pathological conditions affect the tissue distribution and kinetics of administered drugs; as they may alter the magnitude and duration of drug content in targeted organs. Nitroimidazole is a parent compound to a number of derivatives which efficiently fight anaerobic bacteria and mono-cellular parasites. The main aim of the present study was to evaluate the gastrointestinal tissue (GIT) distribution of 125I-metronidazole (125I-MET) and 125I-2-nitroimidazole (125I-NIM) in Escherichia coli (E.coli)-induced gastrointestinal infection in albino mice in comparison to normal 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 125I-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 or125I-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. The study involved the use of seven animal groups each of 5 mice which have treated as follows: one group as a control, one group infected with E.coli, one group injected with125I only, and two E .coli non-infected and two E. coli infected groups each injected with either cold metronidazole or 2-nitroimidazole.Blood was obtained from retro-orbital plexus at 30 min., 60 min., and 180 min after injecting the tracer. Animals were then sacrificed by decapitation under chloroform anesthesia, while blood, GIT, liver and urine were collected at the time of decapitation; and their radioactivity was measured using a γ-counter. Following I.V injection of 125I-MET and 125I-2-NIM, both tracers experienced a comparable average blood level. E.coli infection employed a positive impact on the GIT tissue uptake of the two injected tracers, with higher uptake of 125I-MET than 125I-2-NIM.The hepatic tissue maintained a more stable level of 125I-MET than 125I-2-NIM in normal and in E. Coli infected mice. Data also demonstrated that more than 60% of injected 125I-2-NIM tracer was excreted in urine after 180 min in comparison to only 20% urinary excretion of the injected125I-MET dose.In conclusion, the parallel average blood level of the same injected dose of 125I-2MET and 125I-2NIMsuggested 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 Enramebahistolyticum, 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 appears 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 Trichomonasvaginalis infection than MET.