AI Article Synopsis
- Dolutegravir (DTG) is a first-line HIV treatment that has some limitations regarding tissue penetration and potential metabolic side effects, which have not been thoroughly explored in relation to trace amines—biochemical compounds affecting inflammation and neurological health.
- This study analyzed how DTG affects trace amine levels in male and female Wistar rats over 12 weeks, utilizing blood and tissue samples evaluated through advanced liquid chromatography techniques.
- Findings indicated significant differences in polyamine levels between genders and showed that DTG treatment reduced certain trace amines, although it did not raise major concerns; further clinical studies are suggested to understand DTG’s broader impacts on trace amine profiles in health and disease.
Article Abstract
Background: Dolutegravir (DTG), an integrase strand inhibitor, is currently used as the first-line treatment for HIV. Despite relatively poor tissue penetration, the risk of adverse effects in metabolic and excretory systems should be considered. The trace aminergic system and trace amines are emerging as relevant role players in many chronic diseases that are commonly diagnosed but poorly understood. Trace amines are biogenic amines that are endogenously produced and can also be ingested by the intake of trace amine-rich food. Trace amines are known to differentially regulate inflammatory and neurological outcome.
Objective: This study investigated the effects of DTG on the trace amine profile in a wistar rat model.
Methods: A total of 24 healthy wistar rats were randomly divided into four experimental groups: male and female controls and male and female DTG-treated. Blood and tissue samples were collected following a 12-week DTG administration study. Liquid chromatography-tandem mass spectroscopy (LC-MS/MS) was used to determine trace amine concentrations in urine, plasma, brain, and gastrointestinal tissue.
Results: Current data illustrate that polyamines differ significantly (p < 0.05) between males and females in various matrices. DTG significantly (p < 0.05) reduced jejunal tyramine and urinary synephrine levels.
Conclusion: Data do not raise major concerns about DTG in the context of the trace amine profile. However, given the importance of the dysregulated trace amine profile in various diseased states, including HIV, current data warrant clinical investigation to further evaluate the significance of DTG-associated effects on the trace amine profile.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455829 | PMC |
| http://dx.doi.org/10.1007/s40268-024-00484-4 | DOI Listing |
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