Istraživanje citotoksičnih, genotoksičnih i citogenetičkih učinaka hidrokinona na ljudskim limfocitima periferne krvi u uvjetima in vitro

This study investigated the mechanisms of hydroquinone toxicity and assessed the relationships between its cytotoxic, genotoxic, and cytogenetic effects tested at 8, 140, and 280 μg mL-1 in human peripheral blood lymphocytes exposed for 24 h. The outcomes of the treatments were evaluated using the apoptosis/necrosis assay, the alkaline comet assay, and the cytokinesis-block micronucleus (CBMN) cytome assay. The tested hydroquinone concentrations produced relatively weak cytotoxicity in resting lymphocytes, which mostly died via apoptosis. Hydroquinone’s marked genotoxic effects were detected using the alkaline comet assay. Significantly decreased values of all comet parameters compared to controls indicated specific mechanisms of hydroquinone-DNA interactions. Our results suggest that the two higher hydroquinone concentrations possibly led to cross-linking and adduct formation. Increased levels of DNA breakage measured following exposure to the lowest concentration suggested mechanisms related to oxidative stress and inhibition of topoisomerase II. At 8 μg mL-1, hydroquinone did not significantly affect MN formation. At 140 and 280 μg mL-1, it completely blocked lymphocyte division. The two latter concentrations also led to erythrocyte stabilization and prevented their lysis. At least two facts contribute to this study’s relevance: (I) this is the first study that quantifies the degree of reduction in total comet area measured in lymphocyte DNA after hydroquinone treatment, (II) it is also the first one on a lymphocyte model that adopted the “cytome” protocol in an MN assay and found that lymphocytes exposure even to low hydroquinone concentration resulted in a significant increase of nuclear bud frequency. Considering the limitations of the lymphocyte model, which does not possess intrinsic metabolic activation, in order to unequivocally prove the obtained results further studies using other appropriate cell lines are advised.Cilj ovog istraživanja bio je proučiti mehanizme toksičnosti hidrokinona i odnose između njegovih citotoksičnih, genotoksičnih i citogenetičkih učinaka na ljudskim limfocitima periferne krvi izloženima koncentracijama 8, 140 i 280 μg mL-1 tijekom 24 sata. Posljedice izlaganja testiranom spoju istražene su primjenom testa za otkrivanje stanica u apoptozi i nekrozi, komet-testa u alkalnim uvjetima i tzv. cytome inačice citohalazinom blokiranog mikronukleus-testa. Istražene koncentracije hidrokinona izazvale su relativno nisku citotoksičnost u limfocitima, koji većinom ugibaju apoptozom. Međutim, pri istim koncentracijama primjenom komet-testa uočene su značajne promjene u razinama primarnih oštećenja DNA u odnosu na kontrolu. Statistički značajno snižene vrijednosti svih parametara komet-testa u odnosu na kontrolne stanice upućuju na specifične mehanizme međudjelovanja hidrokinona i DNA. Dobiveni rezultati upućuju na mogućnost nastanka ukriženih veza u molekuli DNA (engl. cross-linking) i nastanak adukata u DNA nakon izloženosti dvjema višim koncentracijama hidrokinona, a povišene vrijednosti lomova u DNA, uočene nakon izlaganja najnižoj ispitanoj koncentraciji, upućuju na veći značaj oksidacijskih oštećenja i utjecaj mehanizama povezanih s inhibicijom enzima topoizomeraze II. Pri koncentraciji 8 μg mL-1 hidrokinon ne izaziva značajan porast broja mikronukleusa. Koncentracije 140 i 280 μg mL-1 potpuno koče diobu limfocita, a ujedno izazivaju i stabilizaciju membrana eritrocita, sprječavajuć njihovu lizu. Dva dobivena rezultata značajan su doprinos postojećim saznanjima o toksičnosti hidrokinona: (I.) Ovo je prvo istraživanje u kojem je izmjereno smanjenje ukupne površine kometa limfocitne DNA nakon izlaganja hidrokinonu; (II.) Ovo je prvo istraživanje u kojem je primijenjena cytome inačica mikronukleus-testa, kojom smo dokazali da izloženost čak i vrlo niskim koncentracijama hidrokinona dovodi do značajno povišene učestalosti nastanka jezgrinih pupova u limfocitima. Uzevši u obzir ograničenja limfocita kao modela, ponajprije nedostatak unutarnje metaboličke aktivacije, za nedvojbenu potvrdu dobivenih rezultata predlažemo nastavak istraživanja i na drugim prikladnim modelima staničnih linija

Različiti učinci samih hlapljivih anestetika ili u kombinaciji s gama-zračenjem od 1 i 2 Gy in vivo na DNA mišje jetre: preliminarno istraživanje

As the number of radiotherapy and radiology diagnostic procedures increases from year to year, so does the use of general volatile anaesthesia (VA). Although considered safe, VA exposure can cause different adverse effects and, in combination with ionising radiation (IR), can also cause synergistic effects. However, little is known about DNA damage incurred by this combination at doses applied in a single radiotherapy treatment. To learn more about it, we assessed DNA damage and repair response in the liver tissue of Swiss albino male mice following exposure to isoflurane (I), sevoflurane (S), or halothane (H) alone or in combination with 1 or 2 Gy irradiation using the comet assay. Samples were taken immediately (0 h) and 2, 6, and 24 h after exposure. Compared to control, the highest DNA damage was found in mice receiving halothane alone or in combination with 1 or 2 Gy IR treatments. Sevoflurane and isoflurane displayed protective effects against 1 Gy IR, while with 2 Gy IR the first adverse effects appeared at 24 h post-exposure. Although VA effects depend on liver metabolism, the detection of unrepaired DNA damage 24 h after combined exposure with 2 Gy IR indicates that we need to look further into the combined effects of VA and IR on genome stability and include a longer time frame than 24 h for single exposure as well as repeated exposure as a more realistic scenario in radiotherapy treatment.Kako se broj radioterapijskih i radioloških dijagnostičkih postupaka iz godine u godinu povećava, tako raste i primjena hlapljivih anestetika za opću anesteziju. Iako se smatralo sigurnim, izlaganje hlapljivim anesteticima može izazvati različite štetne učinke, a u kombinaciji s ionizirajućim zračenjem može izazvati i sinergijske učinke. Međutim, malo se zna o oštećenju DNA koje uzrokuje ova kombinacija u dozama primijenjenima u jednom izlaganju u radioterapiji. Kako bismo saznali više o tome, alkalnim komet-testom analizirali smo oštećenje DNA i odgovor na popravak u jetrenom tkivu muških Swiss albino miševa nakon izlaganja samo izofluranu, sevofluranu ili halotanu, odnosno u kombinaciji sa zračenjem od 1 ili 2 Gy. Uzorci su uzeti odmah (0 h) te 2, 6 i 24 sata nakon izlaganja. U usporedbi s kontrolom, najveća oštećenja DNA utvrđena su u miševa koji su primili halotan, sam ili u kombinaciji sa zračenjem od 1 ili 2 Gy. Sevofluran i izofluran pokazali su zaštitne učinke nakon izlaganja zračenju od 1 Gy, a pri 2 Gy prve nuspojave pojavile su se 24 sata nakon izlaganja. Iako učinci hlapljivih anestetika ovise o metabolizmu jetre, otkrivanje nepopravljenog oštećenja DNA 24 sata nakon kombinirane izloženosti sa zračenjem od 2 Gy upućuje na to da trebamo nastaviti istraživati kombinirane učinke hlapljivih anestetika i ionizirajućega zračenja na stabilnost genoma i obuhvatiti šire razdoblje nakon jednokratne izloženosti (duže od 24 sata). Također treba obuhvatiti višekratna izlaganja kao realističniji scenarij u liječenju radioterapijom

Effectivity of flavonoids on animal model psoriasis – thermographic evaluation

Background and purpose: Psoriasiform lesions are characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes, accompanied by inflammation, leading to a disrupted skin barrier with an abnormal stratum corneum. Psoriasis is a chronic inflammatory disease whose etiopathogenesis has not yet been fully resolved, and therefore there is no standardized therapeutical approach. This study examined the possible positive effects of propolis and its polyphenolic/flavonoid compounds on animal model psoriasis, induced by the Di-n-Propyl Disulfide iritant (PPD), and the possibility to assess usefulness of thermography in psoriatic lesion regression. Material and methods: We monitored the inflammation process by monitoring the total number of inflammatory cells in peritoneal cavity, macrophage spreading index and thermographic scanning. Thermographic is scanning an effective and simplemethod which reproducibly records thermographic images of the examined area. The tested animals were divided into sixteen groups and locally processed during five days with PPD, water and ethanolic extract (WSDP or EEP) of propolis preparations and flavonoids (Epigallocatechin 3-gallate, Quercetin, Chrisin, Curcumin). Results: The results of thermal imaging showed no statistically significant differences in temperature changes on skin locuses of psoriasis formed lesions among the examined groups. The total number of inflammatory cells in peritoneal cavity and the macrophage spreading index were reduced in psoriatic mice treated with test components. Conclusions: These results demonstrate that topical application of propolis and the flavonoids present in propolis may improve psoriatic-like skin lesions by suppressing functional activity of macrophages and ROS production. Taken toghether, it is suggested that propolis and flavonoids offer some protection against psoriatic complications through their roles as inhibitors of inflammation and as free radical scavengers. Thermal imaging was realistic, and can be applicable in examining the inflammatory process in psoriasis and in evaluating the effectiveness of tested substances

Effectivity of flavonoids on animal model psoriasis – thermographic evaluation

Background and purpose: Psoriasiform lesions are characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes, accompanied by inflammation, leading to a disrupted skin barrier with an abnormal stratum corneum. Psoriasis is a chronic inflammatory disease whose etiopathogenesis has not yet been fully resolved, and therefore there is no standardized therapeutical approach. This study examined the possible positive effects of propolis and its polyphenolic/flavonoid compounds on animal model psoriasis, induced by the Di-n-Propyl Disulfide iritant (PPD), and the possibility to assess usefulness of thermography in psoriatic lesion regression. Material and methods: We monitored the inflammation process by monitoring the total number of inflammatory cells in peritoneal cavity, macrophage spreading index and thermographic scanning. Thermographic is scanning an effective and simplemethod which reproducibly records thermographic images of the examined area. The tested animals were divided into sixteen groups and locally processed during five days with PPD, water and ethanolic extract (WSDP or EEP) of propolis preparations and flavonoids (Epigallocatechin 3-gallate, Quercetin, Chrisin, Curcumin). Results: The results of thermal imaging showed no statistically significant differences in temperature changes on skin locuses of psoriasis formed lesions among the examined groups. The total number of inflammatory cells in peritoneal cavity and the macrophage spreading index were reduced in psoriatic mice treated with test components. Conclusions: These results demonstrate that topical application of propolis and the flavonoids present in propolis may improve psoriatic-like skin lesions by suppressing functional activity of macrophages and ROS production. Taken toghether, it is suggested that propolis and flavonoids offer some protection against psoriatic complications through their roles as inhibitors of inflammation and as free radical scavengers. Thermal imaging was realistic, and can be applicable in examining the inflammatory process in psoriasis and in evaluating the effectiveness of tested substances

Primjena alkalnog kometnog testa u istraživanju radioprotektivnih učinaka alkoholnog ekstrakta propolisa i kvercetina na miševima ozračenim gama-zračenjem

The aim of this study was to assess radioprotective effects of quercetin and the ethanolic extract of propolis (EEP) in CBA mice exposed to a single radiation dose 4 Gy (60Co). The mice were treated with 100 mg kg-1 quercetin or EEP a day for three consecutive days either before (pre-treatment) or after gamma-irradiation (therapy). Leukocyte count was determined in blood drawn from the tail vein, and DNA damage in leukocytes was assessed using the alkaline comet assay. Genotoxic effects of the test compunds were also evaluated in non-irradiated mice. The levels of radioprotection provided by both test compounds were compared with those established in mice that were given chemical radioprotector S-(2-Aminoethyl)isothiouronium bromide hydrobromide (AET). Mice that received pre-treatment were less sensitive to irradiation. Mice given the post-irradiation therapy showed a slight but not significant increase in total leukocyte count over irradiated negative control. Quercetin showed better protective properties than EEP in both pre-treatment and therapy, and activated a higher number of leukocytes in non-irradiated mice. The alkaline comet assay suggests that both natural compounds, especially when given as pre-treatment, protect against primary leukocyte DNA damage in mice. At tested concentrations, EEP and quercetin were not genotoxic to non-irradiated mice. AET, however, caused a slight but not significant increase in DNA damage. Although the results of this study show the radioprotective potential of the test compounds, further investigation is needed to clarify the underlying protection mechanisms.Na miševima soja CBA istraženi su radioprotektivni učinci alkoholnog ekstrakta propolisa (AEP) i flavonoida kvercetina primijenjenih u obliku predtretmana i terapije usporedo s izlaganjem gama-zračenju iz izvora 60Co, doze 4 Gy. Testirane tvari injicirane su miševima intraperitonealno u dozi od 100 mg kg-1 tijekom tri uzastopna dana. Nakon završetka pokusa u uzorcima krvi ozračenih miševa utvrđen je ukupni broj leukocita, a razina primarnih oštećenja u DNA izmjerena je primjenom alkalnog kometnog testa. Usporedo su istraženi i mogući genotoksični učinci testiranih tvari na neozračenim miševima. Razine radioprotekcije koju pružaju propolis i kvercetin uspoređene su sa sintetskim radioprotektorom AET-om (S-(2-aminoetil)izotiouronij bromid hidrobromid). Predtretman miševa bilo kojim oblikom radioprotektora pridonosi boljem odgovoru na zračenje. U miševa koji su primili radioprotektore u obliku terapije uočen je mali porast ukupnog broja leukocita u odnosu na ozračenu negativnu kontrolu. Kvercetin je pružio bolju zaštitu od zračenja nego AEP, i u predtretmanu i terapiji, a u neozračenih miševa potaknuo je oslobađanje većeg broja leukocita u odnosu na negativnu kontrolu. Rezultati istraživanja upućuju na to da propolis i njegove fl avonoidne sastavnice, osobito ako su primijenjene prije ozračivanja, mogu učinkovito zaštititi miševe od štetnih učinaka ionizirajućeg zračenja i smanjiti razinu primarnih oštećenja DNA u leukocitima. AEP i kvercetin u testiranim dozama nisu bili genotoksični, za razliku od AET-a koji je izazvao mali porast razine oštećenja DNA u leukocitima neozračenih miševa. Iako rezultati istraživanja upućuju na radioprotektivne učinke testiranih prirodnih spojeva, radi pojašnjenja pretpostavljenih mehanizama radioprotekcije potrebna su daljnja istraživanja

Digital thermography in analysis of temperature changes in Pelophylax ridibundus frog

Background and Purpose: Physiological field of metabolism manipulation tries to elucidate how tissues recuperate after ischemic reperfusion changes, how signal molecules coordinate metabolic pathways and what physiological changes are to be expected in induced artificial hypometabolism or suspended animation in biomedicine. Evolutionary developed mechanisms of lowered metabolism (torpor, hibernation and aestivation) followed by arousals to normal metabolic/thermoregulatory states present perfect models for such studies. In the light of the vast current interest inmanipulating metabolism, natural behavior and adaptations of frogs, makes them among other organisms, an appropriate standard model animal for such studies. The exact measurements of thermal changes of frog’s body temperature correlated with ambient temperature (Ta) changes are essential. Materials and Methods: Male frogs Pelophylax ridibundus (Eurasian Marsh Frog) were kept for 30 days at Ta=8°C (artificial hibernation) and then exposed to Ta = 23°C (artificial arousal). The dynamics of body temperature change over 146 minutes was analyzed with IR camera NEC Thermo tracer TH7102WL and ThermoWEB measuring system. Results and Conclusions: Use of thermography allowed real time thermal measurement of changes in body temperature in frogs in a noninvasive manner. Previous attempts at thermography in hibernating frogs have not been reported, perhaps because of the lack of precision of earlier instruments. New generation cameras have the accuracy and software support to discriminate subtle differences in temperature of different body regions of analyzed frogs and the surrounding environment, as documented in this study

Procjena genotoksičnih učinaka irinotekana i cisplatina na zdrave mišje stanice primjenom alkalnog komet testa

The purpose of cytostatic agents is to act exclusively upon tumor cells, and to inhibit growth or induce tumor cell death by impairing their cell cycle progression. However, the majority of these agents are not specific in their action, and subsequently produce toxic effects on healthy tissues causing significant adverse events in both patients and health professionals exposed to these drugs. Various cytogenetic and molecular biology assays play an important role in the assessment of genotoxic effects related to antineoplastic drugs. Within a short period after exposure to a potentially genotoxic agent, these assays are able to assess the level of cellular DNA damage and/or to monitor the dynamics of DNA repair. Sensitive techniques, such as alkaline comet assay, are of special importance in the detection of primary DNA damage occurring in individual cells regardless of the cell cycle phase. The aim of the study was to assess and compare DNA damage that irinotecan and cisplatin induce in peripheral leukocytes, and normal kidney, liver and brain cells of Swiss albino mice. The results show that both cytostatics produce statistically significant DNA damage in normal cells compared to the control group. Compared to irinotecan, cisplatin has a significantly more potent genotoxic effect on these cells, which may be attributed to various mechanisms of action of the studied drugs.Po svojoj namjeni citostatici bi trebali djelovati isključivo na tumorske stanice, te narušavanjem njihovog staničnog ciklusa spriječiti rast ili izazvati smrt tih stanica. Međutim, većina ovih lijekova je u svom djelovanju nespecifična, zbog čega se toksične posljedice odražavaju i na stanicama zdravih tkiva, a rezultat toga su značajne nuspojave u bolesnika i osoba koje su profesionalno izložene tim lijekovima. U procjeni genotoksičnih učinaka antineoplastičnih lijekova značajnu ulogu imaju različiti citogenetični i molekularno-biološki testovi. Pomoću njih u kratkom vremenskom razdoblju nakon izlaganja nekom potencijalno genotoksičnom agensu, možemo procijeniti razinu oštećenja stanične DNA i/ili pratiti dinamiku njenog popravka. Posebnu važnost imaju tehnike poput alkalnog komet testa koje omogućavaju osjetljivo otkrivanje primarnih oštećenja DNA u pojedinačnim stanicama, neovisno o fazi staničnog ciklusa. Cilj našeg istraživanja je bio ustanoviti i usporediti oštećenja DNA koja izazivaju irinotekan i cisplatina na leukocitima periferne krvi, na zdravim stanicama bubrega, jetre i mozga Swiss albino miševa. Sukladno rezultatima istraživanja oba citostatika dovode do statistički značajnih oštećenja DNA spomenutih zdravih stanica u odnosu na kontrolnu skupinu. Međusobno uspoređujući irinotekan i cisplatinu možemo zamijetiti da cisplatina ima statistički značajno jači genotoksični učinak od irinotekana na spomenute stanice, što pripisujemo različitim mehanizmima djelovanja promatranih citostatika

Procjena genotoksičnih učinaka irinotekana i cisplatina na zdrave mišje stanice primjenom alkalnog komet testa

The purpose of cytostatic agents is to act exclusively upon tumor cells, and to inhibit growth or induce tumor cell death by impairing their cell cycle progression. However, the majority of these agents are not specific in their action, and subsequently produce toxic effects on healthy tissues causing significant adverse events in both patients and health professionals exposed to these drugs. Various cytogenetic and molecular biology assays play an important role in the assessment of genotoxic effects related to antineoplastic drugs. Within a short period after exposure to a potentially genotoxic agent, these assays are able to assess the level of cellular DNA damage and/or to monitor the dynamics of DNA repair. Sensitive techniques, such as alkaline comet assay, are of special importance in the detection of primary DNA damage occurring in individual cells regardless of the cell cycle phase. The aim of the study was to assess and compare DNA damage that irinotecan and cisplatin induce in peripheral leukocytes, and normal kidney, liver and brain cells of Swiss albino mice. The results show that both cytostatics produce statistically significant DNA damage in normal cells compared to the control group. Compared to irinotecan, cisplatin has a significantly more potent genotoxic effect on these cells, which may be attributed to various mechanisms of action of the studied drugs.Po svojoj namjeni citostatici bi trebali djelovati isključivo na tumorske stanice, te narušavanjem njihovog staničnog ciklusa spriječiti rast ili izazvati smrt tih stanica. Međutim, većina ovih lijekova je u svom djelovanju nespecifična, zbog čega se toksične posljedice odražavaju i na stanicama zdravih tkiva, a rezultat toga su značajne nuspojave u bolesnika i osoba koje su profesionalno izložene tim lijekovima. U procjeni genotoksičnih učinaka antineoplastičnih lijekova značajnu ulogu imaju različiti citogenetični i molekularno-biološki testovi. Pomoću njih u kratkom vremenskom razdoblju nakon izlaganja nekom potencijalno genotoksičnom agensu, možemo procijeniti razinu oštećenja stanične DNA i/ili pratiti dinamiku njenog popravka. Posebnu važnost imaju tehnike poput alkalnog komet testa koje omogućavaju osjetljivo otkrivanje primarnih oštećenja DNA u pojedinačnim stanicama, neovisno o fazi staničnog ciklusa. Cilj našeg istraživanja je bio ustanoviti i usporediti oštećenja DNA koja izazivaju irinotekan i cisplatina na leukocitima periferne krvi, na zdravim stanicama bubrega, jetre i mozga Swiss albino miševa. Sukladno rezultatima istraživanja oba citostatika dovode do statistički značajnih oštećenja DNA spomenutih zdravih stanica u odnosu na kontrolnu skupinu. Međusobno uspoređujući irinotekan i cisplatinu možemo zamijetiti da cisplatina ima statistički značajno jači genotoksični učinak od irinotekana na spomenute stanice, što pripisujemo različitim mehanizmima djelovanja promatranih citostatika

Interakcija inhalacijskih anestetika i citostatika

Inhaled anesthetics are often used for inducing or maintaining anesthesia in cancer patients as the length and complexity of the surgical procedure cannot be predicted for it depends on intraoperative surgical and pathohistological findings, and as often as not requires repeated operations for removal or reduction of the primary tumor, regional metastases, recurrence, pathological fractures, or surgery complications. These are easily volatile liquids that enter the body through inhalation, and then, by diffusion through the aleveolocapillary membrane, they are transferred into the blood stream to be transported to all other organs and the central nervous system. Most of the inhaled anesthetics are eliminated from the body through respiration; a portion of them, however, metabolizes in the liver via the cytochrome P450 oxidase family and is excreted via the kidneys, so the issue of their toxicity has always attracted a considerable interest from investigators. Cancer patients receiving cytostatic agents during the perioperative period increase in number every day. Aside from their planned surgery, cancer patients receiving cytostatics also undergo emergency surgery either for their disease complication or for another reason. It is important to understand the pharmacology of cytostatics, their interaction with anesthetics, pharmacokinetics and toxic reactions. Cytostatics and general anesthetics act immunosuppressively and thus compromise the patient’s immune status. In addition, cytostatics depress the myocardium and damage lung function, which can cause serious problems during anesthesia. Each anesthesia as well as each surgery produce stress on the body, and the anesthetics themselves alter the cell immunity so the patients receiving cytostatics during their perioperative period can experience serious general and organ-specific side effects. It would be worth knowing whether any of the most commonly used anesthetics today show an advantage in treating patients withcancer, especially patients receiving chemotherapy, and whether the inhaled anesthetics combined with cytostatics increase, enhance or even suppress the individual effect on various types of cells, above all on tumor cells that can become resistant to therapy for developing the so-called „multidrug resistance“.Inhalacijski anestetici često se primjenjuju za uvod u anesteziju ili za održavanje anestezije kod onkoloških bolesnika zbog toga što se kod uvoda u anesteziju dužina i opseg operacijskog zahvata često ne mogu predvidjeti i ovise o intraoperacijskom kirurškom i patohistološkom nalazu, a nerijetko su potrebne ponavljane operacije zbog uklanjanja ili redukcije primarnog tumora, regionalnih metastaza, recidiva bolesti, udaljenih metastaza, patoloških fraktura ili zbog komplikacija same operacije. To su lako hlapljive tekućine koje u organizam ulaze udisanjem, a zatim difuzijom kroz alveolokapilarnu membranu prelaze u krvotok, krvotokom se dopremaju do svih ostalih organa i do središnjeg živčanog sustava. Veći dio inhaliranih anestetika se eliminira iz organizma respiracijom, me|utim jedan dio metabolizira se u jetri putem obitelji citokrom oksidaza P450 i izlučuje putem bubrega te je pitanje njihove toksičnosti oduvijek izazivalo veliki interes istraživača. Svakodnevno se povećava broj onkoloških bolesnika koji u periperacijskom periodu primaju citostatike. Osim planiranih operacijskih zahvata onkološki bolesnici koji primaju citostatike podvrgavaju se i hitnim operacijskim zahvatima, bilo zbog komplikacija bolesti ili zbog nekog drugog razloga. Važno je razumjeti farmakologiju citostatika, interakciju s anesteticima, farmakokinetiku i toksične reakcije. Citostatici i opći anestetici djeluju imunosupresivno na bolesnika te kompromitiraju njegov imunološki status. Osim toga, citostatici deprimiraju miokard i oštećuju plućnu funkciju, što može izazvati ozbiljne probleme u anesteziji. Svaka anestezija i operacija predstavlja stres za organizam, a sami anestetici mijenjaju staničnu imunost, te bolesnici koji primaju citostatike u perioperacijskom periodu mogu imati ozbiljne opće i organ specifične nuspojave. Bilo bi dobro znati ima li neki od danas najčešće upotrebljavanih anestetika prednost u primjeni kod onkoloških bolesnika, osobito ako ti bolesnici primaju citostatike te da li inhalacijski anestetici i citostatici u kombinaciji povećavaju, potenciraju ili čak suprimiraju pojedinačni učinak na različite vrste stanica, osobito tumorskih stanica koje mogu postati rezistentne na terapiju zbog tzv. „multidrug resistance“

Interakcija inhalacijskih anestetika i citostatika

Inhaled anesthetics are often used for inducing or maintaining anesthesia in cancer patients as the length and complexity of the surgical procedure cannot be predicted for it depends on intraoperative surgical and pathohistological findings, and as often as not requires repeated operations for removal or reduction of the primary tumor, regional metastases, recurrence, pathological fractures, or surgery complications. These are easily volatile liquids that enter the body through inhalation, and then, by diffusion through the aleveolocapillary membrane, they are transferred into the blood stream to be transported to all other organs and the central nervous system. Most of the inhaled anesthetics are eliminated from the body through respiration; a portion of them, however, metabolizes in the liver via the cytochrome P450 oxidase family and is excreted via the kidneys, so the issue of their toxicity has always attracted a considerable interest from investigators. Cancer patients receiving cytostatic agents during the perioperative period increase in number every day. Aside from their planned surgery, cancer patients receiving cytostatics also undergo emergency surgery either for their disease complication or for another reason. It is important to understand the pharmacology of cytostatics, their interaction with anesthetics, pharmacokinetics and toxic reactions. Cytostatics and general anesthetics act immunosuppressively and thus compromise the patient’s immune status. In addition, cytostatics depress the myocardium and damage lung function, which can cause serious problems during anesthesia. Each anesthesia as well as each surgery produce stress on the body, and the anesthetics themselves alter the cell immunity so the patients receiving cytostatics during their perioperative period can experience serious general and organ-specific side effects. It would be worth knowing whether any of the most commonly used anesthetics today show an advantage in treating patients withcancer, especially patients receiving chemotherapy, and whether the inhaled anesthetics combined with cytostatics increase, enhance or even suppress the individual effect on various types of cells, above all on tumor cells that can become resistant to therapy for developing the so-called „multidrug resistance“.Inhalacijski anestetici često se primjenjuju za uvod u anesteziju ili za održavanje anestezije kod onkoloških bolesnika zbog toga što se kod uvoda u anesteziju dužina i opseg operacijskog zahvata često ne mogu predvidjeti i ovise o intraoperacijskom kirurškom i patohistološkom nalazu, a nerijetko su potrebne ponavljane operacije zbog uklanjanja ili redukcije primarnog tumora, regionalnih metastaza, recidiva bolesti, udaljenih metastaza, patoloških fraktura ili zbog komplikacija same operacije. To su lako hlapljive tekućine koje u organizam ulaze udisanjem, a zatim difuzijom kroz alveolokapilarnu membranu prelaze u krvotok, krvotokom se dopremaju do svih ostalih organa i do središnjeg živčanog sustava. Veći dio inhaliranih anestetika se eliminira iz organizma respiracijom, me|utim jedan dio metabolizira se u jetri putem obitelji citokrom oksidaza P450 i izlučuje putem bubrega te je pitanje njihove toksičnosti oduvijek izazivalo veliki interes istraživača. Svakodnevno se povećava broj onkoloških bolesnika koji u periperacijskom periodu primaju citostatike. Osim planiranih operacijskih zahvata onkološki bolesnici koji primaju citostatike podvrgavaju se i hitnim operacijskim zahvatima, bilo zbog komplikacija bolesti ili zbog nekog drugog razloga. Važno je razumjeti farmakologiju citostatika, interakciju s anesteticima, farmakokinetiku i toksične reakcije. Citostatici i opći anestetici djeluju imunosupresivno na bolesnika te kompromitiraju njegov imunološki status. Osim toga, citostatici deprimiraju miokard i oštećuju plućnu funkciju, što može izazvati ozbiljne probleme u anesteziji. Svaka anestezija i operacija predstavlja stres za organizam, a sami anestetici mijenjaju staničnu imunost, te bolesnici koji primaju citostatike u perioperacijskom periodu mogu imati ozbiljne opće i organ specifične nuspojave. Bilo bi dobro znati ima li neki od danas najčešće upotrebljavanih anestetika prednost u primjeni kod onkoloških bolesnika, osobito ako ti bolesnici primaju citostatike te da li inhalacijski anestetici i citostatici u kombinaciji povećavaju, potenciraju ili čak suprimiraju pojedinačni učinak na različite vrste stanica, osobito tumorskih stanica koje mogu postati rezistentne na terapiju zbog tzv. „multidrug resistance“