EXPERIMENTAL APPLICATION OF L-HISTIDINE FOR IMPROVEMENT OF MICROBIOLOGIC AND PATHOLOGIC FEATURES OF SHIGELLOSIS

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