Abstract:
Shigellosis is one of Ihe major diarrheal diseases related lo morbidity, hospitalization,
and death in many developing countries like Bangladesh. The management of
shigellosis lias become more complicated in these countries with the alarmingly
increasing rate of plasmid mediated antibiotic resistance among Shigella organisms
due lo inappropriate and excessive use of different antimicrobials and drugs.
Antibiotic therapy is very expensive lor mass use besides having some side effects. In
the race of the development of resistance of Shigella, we lace the future of having no
effective drugs. So this study is for a search of an alternatives. As Shigellosis is an
acute inflammatory diarrheal disease and because of the anti-inflammatory and
antioxidative properties of L-histidine , the in vivo effects of L-histidine was
evaluated in a rabbit model of acute shigellosis induced by S. Jlexneri 2a infection.
After 24 hour of infection, rabbits (n=102) were given two hourly, 10 mL of 3.8%
solution of L-histidine (n=5I) by intraperitoneal injection or a L-histidine-free
solution that means placebo (n=51). Rabbits were sacrificed after 24 hour of bacterial
inoculation, and at 24, 48, 72 hours of post treatment for histologic, bacteriologic and
biochemical evaluation.
L-histidine concentrations in scrum reached at the highest level after 15 minutes of
administration (809 nM/mL) which declined over 120 minutes. S. Jlexneri induced
typical dysentery characterized by fecal blood, mucus, leukocytosis and severe
colonic inflammation. L-histidine significantly (p<0.05) reduced fecal blood, mucus
and improved diarrhea, fever, leukocytosis and weight loss. L-histidine significantly
(p<0.05) rcduccd mucosal congestion, cellular infiltration and necrotic changes.
Improvement of inflammation indicated by histopathologic grading scores from mild
lo severe which were significantly lower in L-histidine treated groups compared to
placebo groups at 48h and 72h respectively (1.71 ± 0.21 vs 2.36 ± 0.28; 1.02 ± 0.16
vs 2.11 ± 0.20, p<0.05). Macroscopic scores of inflammation ranging from mild to
severe were significantly lower in Ihe in L-histidine treated groups compared lo
placebo groups at 24h, 48h and 72h respectively (8.8 ± 2.8 vs 10.6 ± 3.1; 4.7 ± 2.2 vs
8.7 ± 2.9, p<0.05; 5.0 ± 1.3 vs 8.1 ± 2.8). Mucosal myeloperoxidase activity and
bactcrial counts has a positive correlation with resolution of inflammation due to L-
histidine treatment.
From this study it may be considered that L-histidine has the potential effects in
reducing inflammation and clinical severity of infection with acute shigellosis and
further studies should be earned out to evaluate it’s role in the treatment of
shigellosis in humans. This may be contributed in the therapeutic fight against the
multi-drug resistant Sltigella-induccil infections on millions of people around the
world, particularly in Bangladesh