Razvoj eksperimentalnih modela reaktivirane toksoplazmoze

Neda Bauman; Jelena Srbljanović; Ivana Čolović Čalovski

doi:10.5937/mp75-43421

Neda Bauman Univerzitet u Beogradu, Institut za medicinska istraživanja, Institut od nacionalnog značaja za Republiku Srbiju https://orcid.org/0000-0002-4162-0703
Jelena Srbljanović Univerzitet u Beogradu, Institut za medicinska istraživanja, Institut od nacionalnog značaja za Republiku Srbiju https://orcid.org/0000-0002-9548-4874
Ivana Čolović Čalovski Univerzitet u Beogradu, Medicinski fakultet

DOI: https://doi.org/10.5937/mp75-43421

Ključne reči: reaktivirana toksoplazmoza, in vivo model, kortikosterioidi, ciklofosfamid

Sažetak

Toksoplazmoza je jedna od globalno najrasprostranjenijih zoonoza s obzirom na to da je Toxoplasma gondii ubikvitarna obligatno intracelularna protozoa koja inficira trećinu svetske populacije. Iako je kod imunokompetentnih osoba infekcija najčešće asimptomatska, kod osetljivih kategorija, kao što su fetus i imunokompromitovani pacijenti, toksoplazmoza može dovesti do klinički veoma teških posledica, pre svega kongenitalne i reaktivirane toksoplazmoze (RT). HAART i globalno rastući broj imunosuprimiranih pacijenata koji se leče transplantacijom organa i tkiva a kod kojih toksoplazmoza predstavlja važnu oportunističku infekciju, rezultirao je usmeravanjem istraživačkog fokusa sa HIV+ pacijenata na primaoce transplantata. Postoji hitna potreba za novim, efikasnim i bezbednim antitoksoplazmatskim lekovima jer su aktuelne terapijske opcije u lečenju toksoplazmoze malobrojne i dovode se u vezu sa brojnim neželjenim efektima. Potencijalni hemioterapeutici ispituju se i u in vitro, ali su od većeg značaja rezultati dobijeni u in vivo eksperimentalnim modelima. Jatrogena imunosupresija kod miševa hronično inficiranih T. gondii najčešće se postiže primenom kortikosteroida, kao što su deksametazon u vodi za piće i hidrokortizon putem subkutanih injekcija. Pored kortikosteroida, u upotrebi su i citostatici, pre svega ciklofosfamid, koji je ujedno i među najšire primenjivanim imunosupresivima u transplantacionim protokolima. Velike varijacije u režimu doziranja imunosupresiva u modelima RT ukazuju na potrebu za njihovom optimizacijom. Citostatici i kortikosteroidi, kombinovano primenjeni u odgovarajućim dozama i vremenskim intervalima, simulirali bi najaktuelnije imunosupresivne režime u humanoj transplantacionoj medicini. Naime, i pored raznovrsnosti in vivo eksperimentalnih modela toksoplazmoze, aktuelni trend eksponencijalnog porasta broja transplantiranih pacijenata zahteva bolji uvid u moguće načine za uspostavljanje modela RT. Uspostavljanje održivog modela RT bilo bi značajno za buduća ispitivanja infekcije izazvane T. gondii, a pre svega za sprovođenje hemioterapijskih eksperimenata u cilju otkrivanja potencijalnih novih kandidata za lečenje toksoplazmoze.

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