Naslov (srp)

Toksični efekti smeše olova, kadmijuma, žive i arsena na modelu subakutne izloženosti pacova: protektivno dejstvo probiotika : doktorska disertacija

Autor

Živančević, Katarina, 1993-

Doprinosi

Ćurčić Marijana, 1972-
Đukić-Ćosić, Danijela, 1976-
Antonijević, Biljana, 1964-
Bulat, Petar, 1961-
Buha Đorđević, Aleksandra, 1984-
Bulat, Zorica, 1964-

Opis (srp)

SažetakU okviru ove doktorske disertacije ispitivana je subakutna toksičnost smeše metal(oid)a olova (Pb),kadmijuma (Cd), žive (Hg) i arsena (As) kod pacova, kao i utvrđivanje potencijalnog protektivnogefekta probiotika na umanjenje štetnih efekata ispitivane smeše metal(oid)a. Studija je sprovedenana mužjacima Wistar pacova podeljenim u 8 grupa po 5 jedinki od kojih je jedna grupa bilakontrolna, a 7 grupa je tretirano oralnim putem tokom 28 dana rastućim dozama smeše (MIX:Pb+Cd+Hg+As), od najnižeg nivoa doze - MIX 1 do najvišeg nivoa doze - MIX 5 (mg/kg t.m./dan)(Pb: 0,003, 0,01, 0,1, 0,3, 1; Cd: 0,01, 0,03, 0,3, 0,9, 3; Hg: 0,0002, 0,0006, 0,006, 0,018, 0,06; As:0,002, 0,006, 0,06, 0,18, 0,6), kao i monokomponentnim (5,16×10⁸ CFU/kg/dan; Saccharomycescerevisiae var. boulardii) i multikomponentnim probiotikom (8,78×10⁸ CFU/kg/dan;Saccharomyces cerevisiae var. boulardii, Lactobacillus rhamnosus, Lactobacillus plantarum LP6595, i Lactobacillus plantarum HEAL9) uz smešu najvišeg doznog nivoa MIX 5. Ispitani su nivoitoksičnih metal(oid)a u krvi, hematološki, biohemijski, hormonski i parametri redoks statusa, kao inivoi bioelementa, dok su organi analizirani histopatološki, uz određivanje toksičnih metal(oid)a,bioelemenata i redoks parametara, kao i aktivnosti acetilholinesteraze u mozgu. Modelovan je odnosdoza-odgovor i određene su Benchmark doze za toksične efekte pojedinačnih metal(oid)a u smeši.Značajan porast nivoa Pb, Cd Hg i As u krvi uočen je samo u grupi kojoj je davana najviša doza,dok je akumulacija toksičnih metala dobijena prvenstveno u jetri, bubrezima, mozgu i femuru.Izlaganje najnižoj dozi ispitivane smeše metala dovodi do značanjih promena parametara anemije ukrvi, odnosno sniženja broja eritrocita, hemoglobina, hematokrita, i nivoa gvožđa, kao i značajnogpovećanja parametra oksidativnog stresa, O2.-, PAB i AOPP. Tkiva ispoljavaju različitu osetljivostna oksidativni stres izazvan rastućim dozama smeše toksičnih metala (Pb, Cd, Hg, As).Najizraženije promene zabeležene su mozgu i plućima, dok je u jetri dobijeno smanjenje SOD iGSH pri većini doznih nivoa, dok je MDA snižen u srednjem i dva najviša dozna nivoa ububrezima. Dodatno, više doze smeše Pb, Cd, Hg i As značajno su smanjile aktivnost enzima AChEu mozgu. Histopatološka analiza ukazuje na progresivna oštećenja većine organa pri izloženostismeši metal(a), sa uočljivijim efektima pri većim doznim nivoima. Benchmark analiza utvrdila jepostojanje doza-odgovor pri čemu je najniža BMD vrednost za nivo srednjeg volumena eritrocita(MCV), koji predstavlja kritični toksični efekat za svaki metal(oid) u ispitivanoj smeši i iznosi3,15E-04 mg Pb/kg t.m./dan, 1,05E-03 mg Cd/kg t.m./dan, 2,10E-05 mg Hg/kg t.m./dan i 2,10E-04mg As/kg t.m./dan. Probiotici, monokomponentni i mulitkomponentni, uticali su značajno nasmanjenje Cd, Hg i As u krvi, kao i umanjenje pojedinih metala u jetri, bubrezima, plućima ifemuru. Primena oba probiotika dovodi do normalizovanja izmenjenih vrednosti hematološkihparametara i TAS parametra u krvi, dok primena multikomponentnog probiotika normalizujevrednosti TAS u jetri, IMA u plućima, TOS i O2.- u pankreasu i MDA u testisima i aktivnostenzima acetilholinesteraze u mozgu koji su značajno promenjeni pod uticajem smeše ispitivanihmetal(oid)a. Dobijeni rezultati ukazuju da je mutikomponentni probiotik efikasniji u umanjenjuštetnih efekata ispitivane smeše olova, kadmijuma, žive i arsena u odnosu na monokomponentniprobiotik..

Opis (srp)

Farmacija - Toksikologija / Pharmacy-Toxicology Datum odbrane: 25.07.2025.

Opis (eng)

In this doctoral dissertation, the subacute toxicity of the metal(oid) mixture of lead (Pb), cadmium(Cd), mercury (Hg) and arsenic (As) in rats was examined, as well as the determination of thepotential protective effect of probiotics on reducing the harmful effects of the investigatedmetal(oid) mixture. The study was conducted on male Wistar rats divided into 8 groups of 5individuals, one group was a control group, and 7 groups were treated orally for 28 days withincreasing doses of the mixture (MIX: Pb+Cd+Hg+As), from the lowest dose level - MIX 1 to thehighest dose level - MIX 5 (mg/kg bw/day) (Pb: 0.003, 0.01, 0.1, 0.3, 1; Cd: 0.01, 0.9, 3; Hg:0.0006, 0.018, 0.06; As: 0.002, 0.006, 0.18, 0.6). (5.16×10⁸ CFU/kg/day; Saccharomyces cerevisiaevar. boulardii) and a multicomponent probiotic (8.78×10⁸ CFU/kg/day; Saccharomyces cerevisiaevar. boulardii, Lactobacillus rhamnosus, Lactobacillus plantarum LP 6595, and Lactobacillusplantarum HEAL9) with the mixture of the highest dose level MIX 5. The levels of toxicmetal(oids) in the blood, hematological, biochemical, hormonal and redox status parameters wereexamined, as well as the levels of bioelements, while the organs were analyzed histopathologically,with the determination of toxic metal(oids), bioelements and redox parameters, as well asacetylcholinesterase activity in the brain. A dose-response relationship was modeled andBenchmark doses for the toxic effects of individual metal(oids) in the mixture were determined. Asignificant increase in the levels of Pb, Cd, Hg and As in the blood was observed only in the groupthat received the highest dose, while the accumulation of toxic metals was obtained primarily in theliver, kidneys, brain and femur. Exposure to the lowest dose of the examined metal mixture leads tosignificant changes in the parameters of anemia in the blood, i.e. a decrease in the number oferythrocytes, hemoglobin, hematocrit, and iron levels, as well as a significant increase in theparameters of oxidative stress, O2.-, PAB and AOPP. Tissues exhibit different sensitivity tooxidative stress caused by increasing doses of a mixture of toxic metals (Pb, Cd, Hg, As). The mostpronounced changes were recorded in the brain and lungs, while SOD and GSH were reduced in theliver at most dose levels, while MDA was decreased in the middle and two highest dose levels inthe kidneys. Additionally, higher doses of a mixture of Pb, Cd, Hg and As significantly decreasedthe activity of the AChE enzyme in the brain. Histopathological analysis indicates progressivedamage to most organs upon exposure to the metal(s) mixture, with more noticeable effects athigher dose levels. Benchmark analysis established the existence of a dose-response, where thelowest BMD value for the mean erythrocyte volume (MCV) level, which represents the criticaltoxic effect for each metal(oid) in the tested mixture, is 3.15E-04 mg Pb/kg bw/day, 1.05E-03 mgCd/kg bw/day, 2.10E-05 mg Hg/kg bw/day and 2.10E-04 mg As/kg body weight/day. Probiotics,monocomponent and multicomponent, had a significant effect on the reduction of Cd, Hg and As inthe blood, as well as the reduction of certain metals in the liver, kidneys, lungs and femur. The useof both probiotics leads to the normalization of the changed values of hematological parameters andthe TAS parameter in the blood, while the use of the multicomponent probiotic normalizes thevalues of TAS in the liver, IMA in the lungs, TOS and O2.- in the pancreas and MDA in thetesticles and the activity of the acetylcholinesterase enzyme in the brain, which were significantlychanged under the influence of the mixture of investigated metal(oids). The obtained results indicatethat the multi-component probiotic is more effective in reducing the harmful effects of the examinedmixture of lead, cadmium, mercury and arsenic compared to the mono-component probiotic.

Jezik

srpski

Datum

2025

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 3.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 3.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode

Predmet

OSNO - Opšta sistematizacija naučnih oblasti, Toksikologija

mixture of lead, cadmium, mercury and arsenic, subacute toxicity, mono- and multicomponent probiotic, protective effect, Benchmark doses

OSNO - Opšta sistematizacija naučnih oblasti, Toksikologija

smeša olova, kadmijuma, žive i arsena, subakutna toksičnost, mono- i multikomponentni probiotik, protektivni efekat, Benchmark doze

615.9(043.3)