Abstract
Introduction: Antimicrobial peptides act as innate defense of organisms ranging from plants to insects to humans. They are surface acting agents secreted by all epithelial cells including intestine, which kill microbes. Such peptides possess activities against bacteria, viruses and fungi. As pharmacological induction of these antimicrobial peptides could have potential therapeutic utility, a search for novel molecules that induces production of epithelial antimicrobial peptides has long been sought. Recently, L-isoleucine and its analogues have been found to induce antimicrobial peptides in epithelial surfaces of intestine. So, L-isoleucine might have therapeutic potentials in the management of infectious diarrhea. Aim: The aims of this study were to examine if addition of L-isoleucine to currently recommended (WHO) oral rehydration solution (ORS) reduces the stool weight and/or duration of acute diarrhea. Methods: This was a double blind randomized clinical trial in 51 male children aged 6 to 36 months attending the ICDDRB hospital with acute diarrhea; 26 children received Lisoleucine (2 g/L) added ORS (study) and 25 received ORS without L-isoleucine(control). Other managements were similar. The children remained in the study until recovery from diarrhea but up to a maximum of 5 days. Time to resolution of diarrhea and stool weight were the primary outcomes. Results: Baseline clinical characteristics of the children were comparable between the groups. There was a trend in reduction of stool weight (g) from day 2 ( day1 to day3, study vs. control, stool wt, mean ±SD, 560±240 vs. 563±409, p= 0.93; 407±284 vs. 515±316, p=0.24; 363±284 vs. 651±445, p=0.03 respectively) in the groups receiving ORS with L-isoleucine and the difference was significant on day3. ORS intake (ml) also showed similar trend (day1 to day3 mean ±SD, 410±169 vs. 564±301, p= 0.14; 330±245 vs. 401±226, p=0.33; 312±233 vs. 454±260, p=0.09 respectively), however, the differences were not statistically significant. Duration of diarrhea (hr) was similar in both groups (study vs. control, mean ±SD, 74±38 vs. 75 ±42, p=0.96). Conclusion: Lisoleucine supplemented ORS reduces stool weight and ORS intake in children with acute diarrhea. Further large study is warranted to establish the beneficial effect of L-isoleucine supplemented ORS.
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