Literaturni pregled in primerjava podatkov o absorpciji in metabolizmu parabenov po različnih poteh aplikacije

Veljanovska, Melisa (avtor), Žakelj, Simon (mentor)

Parabeni so alifatski estri p-hidroksibenzojske kisline. Že več desetletij so široko uporabljeni konzervansi v kozmetičnih in farmacevtskih izdelkih ter prehrambni industriji. Prelomne raziskave, ki so poročale o njihovem estrogenem delovanju in povezavi z razvojem raka, so privedle do nasprotujočih si mnenj o njihovi varnosti. Zato intenzivnost njihovega raziskovanja iz leta v leto narašča, kar odraža tudi naraščajoče število znanstvenih objav na to temo. Zaradi polemik o njihovem toksičnem delovanju smo pregledali objavljeno literaturo v zvezi z absorpcijo in metabolizmom po različnih poteh aplikacije, s poudarkom na dermalni aplikaciji. V ta namen smo oblikovali iskalno strategijo po zgledu smernic PRISMA (Prednostne postavke poročanja za sistematični pregled in metaanlize) ter jo uporabili v zbirkah podatkov PubMed in ScienceDirect. Literaturo smo izbrali v skladu z našimi merili in podatke vključili v raziskovalno delo. Prišli smo do zaključka, da se parabeni ne glede na pot izpostavitve hitro absorbirajo in metabolizirajo. Pri dermalni aplikaciji velja izpostaviti, da je absorpcija manjša v primerjavi z drugimi potmi, hkrati je tudi odvisna od formulacije. Po vseh poteh izpostavitve se parabeni metabolizirajo z esterazami in encimi konjugacije, kot so UDP glukuronoziltransferaza, sulfotransferaza in N-acetiltransferaza. Metaboliti, ki nastanejo, so pretežno p hidroksibenzojska kislina in njeni konjugati ter v manjši meri konjugati izhodne spojine. Na sistemsko koncentracijo izhodne spojine vpliva tudi predsistemski metabolizem, predvsem v jetrih in črevesju ter v manjši meri v koži. Zaradi obsežnega metabolizma se nespremenjene izhodne spojine izloči zelo malo oz. skoraj nič, torej je izpostavljenost organizma metabolno nespremenjenim parabenom, ki naj bi izkazovali toksikološke učinke, majhna ne glede na način aplikacije. Parabeni se izločajo hitro, pretežno z urinom. Kopičenja v organizmu v raziskavah niso opazili. Obstoječe toksikološke raziskave ne odgovarjajo na vprašanje, ali so parabeni lahko zdravju škodljivi ob dolgoročni izpostavljenosti koncentracijam, ki so znotraj dovoljenih vrednosti. Ugotovili smo, da farmakokinetične raziskave ne odgovarjajo na vprašanje, ali v toksikološko pomembni koncentraciji pridejo do mest v organizmu, kjer bi lahko delovali toksično oz. ali sploh pridejo do mest, kjer bi lahko delovali toksično, kar je predvsem posledica obsežnega metabolizma.

• Jezik: Slovenski jezik
• Ključne besede: absorpcija, dermalna aplikacija, metabolizem, parabeni
• Vrsta gradiva: Diplomsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2021
• PID: 20.500.12556/RUL-130079
• Datum objave v RUL: 10.09.2021

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Literature review and comparison of parabens’ absorption and metabolism data following different routes of their application

Izvleček

Parabens are aliphatic esters of p-hydroxybenzoic acid and have been widely used as preservatives in cosmetics, pharmaceuticals and food industry for many decades. Breakthrough reaserch, which linked them to estrogenic activity and development of cancer, has led to conflicting opinions about their safety. As a result, the intensity of their reaserch increases year by year, as shown by an increasing number of published scientific papers. Due to controversies about their toxicity, we reviewed the published literature covering the absorption and metabolism of parabens following different routes of application with an emphasis on dermal application. To this end, we developed a search strategy based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used it in the PubMed and ScienceDirect databases. We selected the literature according to our criteria and included the obtained data in our research. We concluded that parabens are readily absorbed and metabolized regardless of the route of exposure. Absorption after dermal exposure is lower compared to other routes, moreover it depends on the formulation. Through all routes of exposure, parabens are metabolised by esterases and conjugation enzymes such as UDP-glucuronosyltransferase, sulfotransferase and N acetyltransferase. The resulting metabolites are predominantly p-hydroxybenzoic acid and its conjugates and to a lesser extent conjugates of the parent compound. In addition systemic concentration of the parent compound is affected by presystemic metabolism, mainly in liver and intestine and to a smaller degree in the skin. Due to the extensive metabolism, very little or no unchanged parent compound is excreted. Therefore, exposure to metabolically unchanged parabens, which are supposed to express toxicological effects, is low regardless of the route of application. Parabens are excreted rapidly, predominantly in the urine. Bioaccumulation was not observed in the studies. Existing toxicological research do not answer the question of whether parabens can be harmful in long-term human exposure to permitted concentrations. We concluded that pharmacokinetic researches do not answer the question whether they reach an active site in organism in toxicologically important concentrations, mainly due to their extensive metabolism.

• Ključne besede: absorption, dermal application, metabolism, parabens