Določitev koncentracij retinoidov in statusa encima paraoksonaza 1 pri bolnikih s psihiatričnimi obolenji, zdravljenih s psihotropnimi zdravili

Debevec, Eva (avtor), Pečar Fonović, Urša (mentor), Esteban Mozo, Javier (komentor)

Psihiatrični bolniki, ki se zdravijo s psihotropnimi zdravili, so dovzetni za presnovne spremembe, nagnjeni k razvoju srčno-žilnih bolezni in presnovnega sindroma ter imajo krajšo pričakovano življenjsko dobo od splošne populacije, predvsem zaradi pridruženih obolenj. Oksidativni stres in vnetje sta poleg drugih dejavnikov prisotna pri razvoju in napredovanju psihiatričnih ter srčno-žilnih bolezni. Retinoidi in encim paraoksonaza 1 (PON1) delujejo antioksidativno, protivnetno in so vključeni v potek psihiatričnih bolezni pa tudi srčno-žilnih obolenj in presnovnih procesov, zato so predmet raziskav pri psihiatričnih bolnikih. Namen magistrske naloge je bil v serumu 73 psihiatričnih bolnikov izmeriti koncentracije retinoidov retinola (RO) in retinil palmitata (RePa) ter določiti status PON1 (aktivnosti PON1 in genotip Q192R). Zatem je bil naš cilj ugotoviti ali ima zdravljenje s psihotropnimi zdravili vpliv na koncentracijo RO in status PON1. Koncentracije RO in RePa v serumu smo določili s tekočinsko kromatografijo visoke ločljivosti z UV-detekcijo (HPLC-UV). Encimske aktivnosti PON1: laktonazno, CMPAzno, arilesterazno in arilesterazno z dodatkom soli smo določili spektrofotometrično z uporabo ne-organofosfatnih substratov dihidrokumarina (DHC), 4-(klorometil)fenil acetata (CMPA) in fenil acetata (PA) brez dodane soli ter z dodano soljo. Genotip Q192R smo določili tako, da smo grafično predstavili CMPAzno aktivnost in arilesterazno aktivnost z dodatkom soli ter razločili genotip QQ, QR in RR. Izračunali smo tudi alelske frekvence. Določene koncentracije RO smo primerjali s prej objavljenimi raziskavami na psihiatričnih bolnikih in ugotovili, da so v istih obsegih. Ugotovili smo, da RePa v krvi ni bil povišan in ni nakazoval na toksičnost vitamina A ali postprandialno povečanje. Izmerjene vrednosti laktonazne, CMPAzne, arilesterazne in arilesterazne aktivnosti z dodatkom soli so bile primerljive s prejšnjimi raziskavami na psihiatričnih bolnikih. Funkcionalni genotip QQ smo določili pri 32 bolnikih, QR prav tako pri 32, ter RR pri 9 bolnikih. Izračunane alelske frekvence so znašale 0,66 za alel Q in 0,34 za alel R in so pravilno ustrezale kavkazijski rasi, kamor spadajo bolniki. Prve ugotovitve kažejo, da bi psihotropna zdravila lahko imela vpliv na serumske koncentracije RO in status PON1, a je pred potrditvijo potrebna nadaljnja poglobljena preučitev. Raziskava je del večjega raziskovalnega projekta, ki še poteka. Izmerjene koncentracije retinoidov, aktivnosti PON1 in izpeljan genotip Q192R bodo tako predmet nadaljnjih raziskav.

• Jezik: Slovenski jezik
• Ključne besede: retinoidi, retinol, paraoksonaza 1, status PON1, psihiatrični bolniki, psihotropna zdravila
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2022
• PID: 20.500.12556/RUL-141301
• Datum objave v RUL: 28.09.2022

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Determination of retinoids’ concentrations and paraoxonase 1 status in psychiatric patients treated with psychotropic drugs

Izvleček

Psychiatric patients treated with psychotropic drugs are susceptible to metabolic alterations, prone to develop cardiovascular diseases (CVDs) and metabolic syndrome and present reduced life expectancy, generally due to the comorbid conditions. Oxidative stress and inflammation, along with various other factors, are present in the evolution and progression of psychiatric conditions, as well as CVDs. Retinoids and paraoxonase 1 (PON1) are involved in the regulation of oxidative stress, inflammation, and body metabolism and have been shown to be altered in psychiatric diseases. This study aimed to determine concentrations of retinoids retinol (RO) and retinyl palmitate (RePa) and PON1 status (PON1 activities and Q192R inferred genotype) in the serum of 73 psychiatric patients with a severe mental disorder and to assess whether the psychotropic treatment had an impact on RO serum concentrations and PON1 status. RO and RePa were determined by high-performance liquid chromatography with UV detection (HPLC-UV). PON1 lactonase, CMPAse, arylesterase, and saline arylesterase activities were determined spectrophotometrically, using non-organophosphate substrates dihydrocoumarin (DHC), 4-(chloromethyl)phenyl acetate (CMPA) and phenyl acetate (PA) in low and high salt conditions, respectively. PON1 Q192R genotype was inferred from a graph presenting CMPAse versus saline arylesterase activities. The measured RO concentrations were within the range of previously published studies in psychiatric patients. RePa levels did not suggest vitamin A toxicity or postprandial increase. Measured lactonase, CMPAse, arylesterase, and saline arylesterase activities were comparable to the existing studies in psychiatric patients. Functional genotype QQ was deduced in 32, QR in 32, and RR in 9 individuals, with allelic frequencies of 0.66 for Q and 0.34 for R allozyme and hence, correspond to those of Caucasian populations. Preliminary findings suggest that psychotropic drugs could affect serum RO concentrations and PON1 status. However, a further in-depth research is warranted. This study was a part of a broader on-going research project. Thus, the determined retinoid concentrations and PON1 status will be the subject of further research.

• Ključne besede: retinoids, retinol, paraoxonase 1, PON1 status, psychiatric patients, psychotropic drugs