Title Endokanabinoidni sustav – njegova uloga u zdravlju i bolesti
Author Desiree - Željka Brkić
Mentor Miranda Mladinić Pejatović (mentor)
Committee member Jelena Ban (predsjednik povjerenstva)
Committee member Miranda Mladinić Pejatović (član povjerenstva)
Committee member Mirela Sedić (član povjerenstva)
Granter University of Rijeka (Faculty of Biotechnology and Drug Development) Rijeka
Defense date and country 2017-09-22, Croatia
Scientific / art field, discipline and subdiscipline BIOTECHNICAL SCIENCES Biotechnology
Abstract Endokanabinoidni sustav skup je enzima, receptora i lipidnih molekula koji igraju
važnu ulogu u fiziologiji čovjeka. Distribuiran u mozgu i na periferiji, ovaj sustav sudjeluje u
održavanju energetske homeostaze poticanjem apetita i sprječavanjem povraćanja, smanjenju
širenja upale nakon ozlijede tkiva te općoj kvaliteti života ublažavanjem boli i grčenja mišića
kod teških patofizioloških stanja. Navedeni učinci samo su neke od uloga koje imaju
kanabinoidi u ljudskom organizmu, a iscrpna istraživanja provode se u svrhu legalizacije
njihove kliničke primjene.
Trenutno dostupni lijekovi poznatog omjera fitokanabinoida poput oromukoznog
spreja Sativex® primjenjuju se prvenstveno za olakšavanje mišićnog spazma i urgentne
inkontinencije kod multiple skleroze, a preostala dva (Marinol® i Cesamet®) dolaze u formi
kapsula i propisuju se u SAD-u, Kanadi, Novom Zelandu i diljem Europe zbog antiemetičkih
svojstava (karcinom) te kao stimulatori apetita (AIDS). U Republici Hrvatskoj od 15.
listopada 2015. godine legalizirana je primjena medicinskog kanabisa. Potencijal u narednim
godinama leži u povećavanju tonusa endogenih ekvivalenata tetrahidrokanabinola (THC-a)
inhibicijom njihovih hidrolaza, te CB2 selektivnih liganada koji nemaju psihotropne učinke.
Cilj ovog rada bio je obraditi pozitivne i negativne učinke ove skupine molekula na
zdravlje čovjeka. Značajno antikancerogeno djelovanje zabilježeno je apliciranjem agonista
kanabinoidnih receptora u in vitro i in vivo modelima najtežeg oblika tumora mozga. Osim
inhibicije angiogeneze, agonisti CB1 i CB2 receptora spriječavaju rast tumorskog tkiva
stimulacijom de novo sinteze ceramida i aktivacijom stresnog odgovora endoplazmatskog
retikuluma koji uzrokuje autofagijom-posredovanu smrt tumorskih stanica. S palijativnog
aspekta, nedavno je otkriven antinociceptivni mehanizam kojim ova skupina molekula djeluje
na područje mozga zaduženo za procesiranje boli supresijom GABAergičke transmisije.
Ovakav pristup daje nadu za razvoj novih terapeutskih pristupa za smanjenje boli kod bolesti
poput reumatoidnog artritisa, dijabetičke polineuropatije, fibromialgije i čak epilepsije. Pritom
valja imati na umu da najpotentniji kanabinoidni pripravci sadrže psihoaktivni THC koji
usljed dugoročne izloženosti vodi ka ovisnosti, depresiji i gubitku pamćenja, a pokazao se
rizičnim faktorom u razvoju mentalnih bolesti. Osim toga, ovaj članak stavlja naglasak na
negativan učinak THC-a na fertilitet muškaraca, proces spermatogeneze i funkciju spermija
usljed promjene u ravnoteži endokanabinoida spolnog sustava.
Abstract (english) The endokanabinoid system combines a group of enzymes, receptors and lipid
molecules which play an important role in human physiology. Distributed in the brain and in
the periphery,this system participates in maintaining energy homeostasis by stimulating
appetite and preventing vomiting, reducing inflammation after tissue injury and raising
overall quality of life by alleviating pain and muscle cramps in severe pathophysiological
conditions. The aforementioned effects are small part of the potency of cannabinoids, and
extensive research is carried out in order to legalize their clinical application.
Currently available drugs with known phytokanabinoid ratio such as Sativex® are
primarily used to relieve muscular spasms and urgent incontinence in multiple sclerosis, while
the remaining two (Marinol® and Cesamet®) are prescribed in the United States, Canada,
New Zealand and throughout Europe due to antiemetic properties (carcinoma) and as an
appetite stimulator (AIDS). In the Republic of Croatia since October 15th 2015, the use of
medical cannabis is legalized. Potential in the coming years lies in increasing tone of
endogenous THC equivalents by inhibiting their hydrolysis, and development of CB2
selective ligands which do not exhibit psychotropic effects.
The aim of this paper was to address the positive and negative effects of this group of
molecules on human health. Significant anticancer activity was observed by applying
cannabinoid receptor agonists in in vitro and in vivo models of the most malignant brain
tumor. In addition to inhibition of angiogenesis, CB1 and CB2 receptor agonists inhibited
tumor tissue growth by stimulating de novo synthesis of ceramide and activating ER stress
response that causes autophagy-mediated death of tumor cells. From a palliative point of
view, an antinociceptive mechanism has recently been discovered by which this group of
molecules acts on the brain region responsible for processing pain by suppressing GABAergic
transmission. This approach gives hope in the future to reduce pain in diseases such as
rheumatoid arthritis, diabetic polyneuropathy, fibromyalgia and even epilepsy. It should also
be considered that the most potent cannabinoid-based drugs contain psychoactive THC which,
after long-term exposure, leads to addiction, depression and memory loss, and also has shown
to be a risk factor for development of mental illnesses. Additionally, this article highlights the
negative impact on male fertility, spermatogenesis, and sperm function of THC due to
changes in the balance of endocannabinoids located in the male reproductive system.
Keywords
endokanabinoidni sustav
karcinom
bol
multipla skleroza
neplodnost
HPGos
Keywords (english)
endocannabinoid system
cancer
pain
multiple sclerosis
infertility
HPG-axis
Language croatian
URN:NBN urn:nbn:hr:193:406354
Study programme Title: Biotechnology and drug research Study programme type: university Study level: undergraduate Academic / professional title: sveučilišni/a prvostupnik/prvostupnica biotehnologije i istraživanja lijekova (sveučilišni/a prvostupnik/prvostupnica biotehnologije i istraživanja lijekova)
Type of resource Text
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Created on 2017-11-03 12:56:07