Direktni farmakološki efekti fulerenola C60(OH)24 na modelu izolovanog glatkog mišića pacova i uloga antioksidativnog sistema

Abstract

Fuleren C60 je alotropska modifikacija ugljenika i on, kao i njegovi derivati, već imaju značajan uticaj na razvoj biomedicinske nanotehnologije. Potencijal nanočestica je veliki, a u slučaju fulerena najveći je njegova primena kao finog biomarkera u molekularnoj dijagnostici. Ispitivanja polihidroksilovanih derivata fulerena pokazali su da oni imaju širok spektar bioloških efekata. Fulerenol C60(OH)24, vodorastvorni derivat fulerena C60, privlači veliku pažnju istraživača. Najviše je ispitivana njegova sposobnost fotosenzitivnosti, kao i sposobnost uklanjanja slobodnih radikala (free radical “sponge” ili free radical scavenger). Takođe, u žiži interesovanja su i anitproliferativna i antikancerogena dejstva ove supstance. Zbog specifične strukture koja podseća na fudbalsku loptu, kandidat je za ulogu nosača supstanci i lekova. Ovakva primena lekova omogućila bi njihovo specifično delovanje na ciljne ćelije ili tkivo. Pokazano je, takođe, da fulerenol ima sposobnost interakcije sa dsDNK, što je veoma značajno sa aspekta razumevanja penetracije ove nanočestice kroz membranu ćelije i njegove intraćelijske aktivnosti. Potencijalna široka primena fulerenola u biomedicini zahteva i obimna farmakološka i toksikološka ispitivanja. Do sada ima malo rezultata farmakoloških ispitivanja fulerenola a direktni farmakološki efekti dobijeni aplikacijom fulerenola na izolovane organe koji poseduju glatku muskulaturu su sporadično ispitivani. S druge strane, supstanca koja se već dugo istražuje ali je, po nekima, i dalje nedovoljno prisutna u farmakologiji je dimetil sulfoksid (DMSO). Osim što je odličan rastvarač, topikalni analgetik i nosač supstanci, DMSO-u se pripisuje sposobnost uklanjanja slobodnih radikala i smatra se da ima pozitivne efekte na oštećenja kardiovaskularnog sistema, centralnog nervnog sistema, bubrežna oboljenja, defekte u strukturi vezivnog tkiva itd. Promene koje fulerenol i DMSO mogu izazvati na kontraktilnost glatke muskulature su izuzetno važne za mogućnost njihove šire primene u medicini i farmakologiji. Ileum je kao deo digestivnog trakta, veoma značajan model sistem za izučavanje dejstva supstance koja bi se potencijalno mogla koristiti u farmakologiji. Uterus pokazuje promene tokom mesečnog ciklusa, kako u kontraktilnosti, tako i u sastavu mikroflore i aktivnosti enzima antioksidativne zaštite. Ispitivane supstance mogu uticati na promene parametara kao što su: frekvenca, amplituda, trajanje i smer propagacije kontrakcija.

Fullerene (C60) is the carbon allotrope and as its derivatives already has a significant impact on biomedical nanotechnology. The potential of nanoparticles is large but one of the most relevant biological features of fullerene is its application as a biomarker in molecular diagnostics. Polyhidroxylated fullerene derivatives have been shown to display a wide range of biological effects. Fullerenol C60(OH)24, as a soluble derivative of fullerene C60, attracts the attention of a number of researchers. The most studied features of fullerenol are photosensitization and the ability to quench various free radicals, behaving as a free radical “sponge” or free radical scavenger. Anitproliferative and anti-cancer properties of this substance are also in the spotlight. Due to its specific structure that resembles a soccer ball, fullerenol is a candidate for a drug carrier. This could enable specific action on target cells or tissue. Ability of fullerenol to interact with dsDNK has also been demonstrated, which is very important in understanding the penetration of nanoparticles through the cell membrane and their intracellular activities. Potentially wide application of fullerenol in biomedicine requires extensive pharmacological and toxicological investigations. Pharmacological tests and direct pharmacological effects obtained from application of fullerenol on isolated organs that possess smooth musculature were investigated only sporadically. On the other hand, dimethyl sulfoxide (DMSO) has long been investigated but is, according to some, still insufficiently represented in the pharmacology. Besides being an excellent solvent, topical analgetic and drug carrier, DMSO has the ability to remove free radicals and is considered to have positive effects on the damage of cardiovascular system, central nervous system, renal disease, defects in the structure of connective tissue etc. Both fullerenol and DMSO can cause changes in the contractility of smooth muscles, which is extremely important for their potentially wider application in pharmacology. Ileum, as a part of the digestive tract is an important model system for the investigation of a substance that could potentially be used in pharmacology. Uterus contractility, microflora and the activity of antioxidative enzymes change during menstrual cycle. Investigated substances can change parameters of contraction, such as: frequency, amplitude, duration and direction.