In vivo i in vitro ispitivanja biotoksičnosti polistirenskih mikro- i nanočestica

Abstract

Mikroplastika i nanoplastika značajno doprinose zagađenju životne sredine. Još uvek nije dovoljno poznato kakav je uticaj MP/NP na funkciju ćelija, kao i na zdravlje životinja i ljudi. U ovom istraživanju je pokazano da nakon oralnog unošenja, fluorescentno obeležene polistirenske (engl. polystyrene, PS) mikročestice (engl. microparticles, MP) i nanočestice (engl. nanoparticles, NP) prolaze kroz digestivni sistem miša, akumuliraju se i agregiraju u različitim tkivima i izazivaju funkcionalne promene u ćelijama i organima. Korišćenje kohlearnog eksplanta kao novog in vitro modela, ispitana je interakcija PS-MP/NP sa ćelijama unutrašnjeg uha u kome su detektovani agregati i heteroagregati PS čestica. PS-MP/NP su se akumulirale u intersticijumu testisa tretiranih životinja, oko seminifernih tubula, što je uzrokovalo statistički značajno smanjenje koncentracije testosterona u serumu. Splenociti tretiranih mužjaka su povećano sekretovali IL-12p35 i IL-23, dok su testovi citotoksičnosti i genotoksičnosti ukazivali na smanjenu vijabilnost ćelija i povećano oštećenje DNK u ćelijama slezine. Kod mužjaka je zabeležen anksiogeni odgovor nakon primene PS-MP/NP, dok je u uzorcima tkiva hipokampusa tretiranih ženki detektovana povećana ekspresiju Bax i Nlrp3 gena, što ukazuje na proapoptotički i proinflamatorni uticaj PS-MP/NP. Jedan od zaključaka ove disertacije je da efekti PS-MP/NP zavise od pola organizma koji je izložen njihovom delovanju, što otvara vrata budućim istraživanja u cilju sprečavanja štetnih efekata PS čestica na zdravlje ljudi.

Commercially manufactured or generated through environmental degradation, microplastics (MPs) and nanoplastics (NPs) considerably contribute to environmental pollution. There is a knowledge gap in how exposure to MPs/NPs changes cellular function and affects animal and human health. Here, we demonstrate that after oral uptake, fluorescent polystyrene (PS) nanoparticles pass through the mouse digestive system, accumulate and aggregate in different organs, and induce functional changes in cells and organs. Using cochlear explant as a novel in vitro system, we confirmed the consequences of PS-MP/NP interaction with inner ear cells by detecting aggregates and hetero-aggregates of PS particles in hair cells. The testes of treated males accumulated MPs/NPs in the interstitial compartment surrounding the seminiferous tubules, which was associated with a statistically significant decrease in testosterone levels. Male mice showed increased secretion of interleukins (IL-12p35 and IL-23) by splenocytes while cyto- and genotoxicity tests indicated impaired cell viability and increased DNA damage in spleen tissue. Males also showed a broad range of anxiogenic responses to PS nanoparticles while hippocampal samples from treated females showed an increased expression of Bax and Nlrp3 genes, indicating a pro-apoptotic/proinflammatory effect of PS treatment. Taken together, induced PS effects are also gender-dependent, and therefore, strongly motivate future research to mitigate the deleterious effects of nanosized plastic particles.