The efficacy and toxicity of antineoplastic antimetabolites: Role of gut microbiota

How Hydroxyurea Alters the Gut Microbiome: A Longitudinal Study Involving Angolan Children with Sickle Cell Anemia

“…Hydroxyurea is considered an antineoplastic antimetabolite drug and was initially used as a chemotherapeutic agent until its benefits for SCA treatment were recognized more than 30 years ago [ 9 ]. It is reported that most of the antineoplastic antimetabolites decrease the alpha diversity of gut microbiota [ 21 ], which was consistent with our results. However, the same study also reported that most of these drugs can also induce gut microbiota dysbiosis, particularly the imbalance of the F/B ratio, and reduce the SCFA-producing gut species, probably due to the toxicity induced [ 21 ].…”

“…It is reported that most of the antineoplastic antimetabolites decrease the alpha diversity of gut microbiota [ 21 ], which was consistent with our results. However, the same study also reported that most of these drugs can also induce gut microbiota dysbiosis, particularly the imbalance of the F/B ratio, and reduce the SCFA-producing gut species, probably due to the toxicity induced [ 21 ]. This was not in agreement with our results, but it is important to take into consideration that this population suffers from a chronic disease and the clinical benefits brought by hydroxyurea administration could surpass the disadvantages/adverse effects in the majority of cases.…”

“…The composition and metabolic ability of the gut microbiome have a major role in pharmacokinetics and could determine drug toxicity and clinical efficacy through its impact on chemical transformation [ 19 , 21 , 37 ]. Conversely, drugs can also change the microbial community composition and function by altering the intestinal microenvironment, microbial metabolism, or bacterial growth [ 37 ].…”

“…Since the microbiome is highly individualized, different patients may have distinct responses to the absorption, distribution, and metabolism of certain drugs [ 19 ]. On the other hand, this also provides a significant potential for biomarkers to predict drug responses, and correct dosage and could optimize a certain therapy, promoting a more personalized approach [ 21 ].…”

Measurement of the effect of 5-Fluorouracil as an anticancer drug on the nitric oxide levels on HepG2 cell line

“…After it turns into an active deoxynucleotide, it acts as an antimetabolite; this stops DNA synthesis by blocking turns of deoxyuridylic acid into thymidylic acid by thymidylate synthetase enzyme, which slows down tumors' growth [19]. Antimetabolites are analogous to the nucleotides found in DNA and RNA [20]. Because those medications are so close to natural substances found in the cells, they effectively fool the body into thinking they are biological nucleotide bases.…”