Safety evaluation of 5-hydroxytryptophan and S-(2-aminoethyl)isothiouronium bromide hydrobromide on rodent lungs.
Journal
Indian journal of pharmacology
ISSN: 1998-3751
Titre abrégé: Indian J Pharmacol
Pays: India
ID NLM: 7902477
Informations de publication
Date de publication:
01 Jan 2024
01 Jan 2024
Historique:
received:
31
03
2023
accepted:
29
01
2024
medline:
8
3
2024
pubmed:
8
3
2024
entrez:
8
3
2024
Statut:
ppublish
Résumé
During the past few decades, various compounds have been researched for their potential as radioprotectants, and many of them were found to be safe and effective in several preclinical models. However, many of these compounds were found to have serious adverse effects when evaluated in clinical settings, thereby making them unsuitable for human applications. 5-hydroxytryptophan (5-HTP) and S-(2-aminoethyl) isothiouronium bromide hydrobromide (AET) act in a synergistic fashion to promote radioprotection. The present study primarily emphasizes the safety of fixed dose of 5-HTP + AET in the lungs of C57BL/6 mice, a well-known model used in drug safety studies. Post-administration of the combination of HTP+AET at specific time points, blood and bronchoalveolar lavage fluid (BALF) were collected for the analysis of inflammatory and oxidative stress markers of the lungs. Thereafter, the mice were sacrificed and the lungs were dissected out, weighed, and fixed in formalin for histopathological studies. The inflammatory biomarkers: tumor necrosis factor-alpha and interleukin-10 and oxidative stress biomarkers: 8-isoprostane and 8-hydroxy-2'-deoxyguanosine were found to have normal levels in blood and BALF in both control and treatment groups, which was further supported by normal histological findings. In addition, other endpoints such as food and water intake were found to be within normal limits. The present safety study reflects that the combination has no adverse effects on the lungs of the experimental mouse. Further, evaluation in higher mammals including nonhuman primates is essential prior to validation of the safety of the combination in humans.
Identifiants
pubmed: 38454586
doi: 10.4103/ijp.ijp_176_23
pii: 01363791-202456010-00006
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
28-36Informations de copyright
Copyright © 2024 Copyright: © 2024 Indian Journal of Pharmacology.
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