Ketamine is a dissociative anaesthetic used to induce general anaesthesia in humans and laboratory animals. Due to its hallucinogenic and dissociative effects, it is also used as a recreational drug. ...Anaesthetic agents can cause toxic effects at the cellular level and affect cell survival, induce DNA damage, and cause oxidant/antioxidant imbalance. The aim of this study was to explore these possible adverse effects of ketamine on hepatocellular HepG2 and neuroblastoma SH-SY5Y cells after 24-hour exposure to a concentration range covering concentrations used in analgesia, drug abuse, and anaesthesia (0.39, 1.56, and 6.25 µmol/L, respectively). At these concentrations ketamine had relatively low toxic outcomes, as it lowered HepG2 and SH-SY5Y cell viability up to 30 %, and low, potentially repairable DNA damage. Interestingly, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) remained unchanged in both cell lines. On the other hand, oxidative stress markers superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) pointed to ketamine-induced oxidant/antioxidant imbalance.
Ochratoxin A (OTA) and citrinin (CTN) are nephrotoxic mycotoxins often found together in grain. The aim of this study was to measure their accumulation in the kidney and liver of adult male Wistar ...rats, see how it would be affected by combined treatment, and to determine if resveratrol (RSV) would decrease their levels in these organs. The rats received 125 or 250 mg/kg bw of OTA by gavage every day for 21 days and/or 20 mg/kg bw of CTN a day for two days. Two groups of rats treated with OTA+CTN were also receiving 20 mg/kg bw of RSV a day for 21 days. In animals receiving OTA alone, its accumulation in both organs was dose-dependent. OTA+CTN treatment resulted in lower OTA but higher CTN accumulation in both organs at both OTA doses. RSV treatment increased OTA levels in the kidney and liver and decreased CTN levels in the kidney. Our findings point to the competition between CTN and OTA for organic anion transporters 1 and 3.
ENDEMSKA NEFROPATIJA U HRVATSKOJ Jelaković, Bojan; Dika, Živka; Karanović, Sandra ...
Liječnički vjesnik,
05/2015, Letnik:
137, Številka:
3-4
Journal Article
Recenzirano
Odprti dostop
Endemska nefropatija (EN) kronična je tubulointersticijska nefropatija aristolohične kiseline (AAN) koja se javlja u stanovnika određenih sela u dolinama velikih pritoka Dunava na jugoistoku Europe ...uključujući i Hrvatsku. Oboljeli od EN-a imaju znatno veću učestalost karcinoma prijelaznog epitela mokraćovoda nego opća populacija. Danas se smatra da je A:T transverzija gena p53 »potpisna« mutacija za aristolohičnu kiselinu koja je uzrok endemske nefropatije. Postojeći kriteriji za EN su zastarjeli, neujednačeni (tri vrste kriterija) te nisu u skladu s novim preporukama za klasifikaciju bubrežnih bolesti. Stoga su na temelju sadašnjih znanja i stručnosti grupe znanstvenika i stručnjaka iz svih zemalja s EN-om, kao i svijeta u kojem je AAN opisan stvoreni novi dijagnostički kriteriji i nova klasifikacija stanovništva endemskih sela na simpoziju o EN-u. EN je velik javnozdravstveni problem pa bi nam sadašnja znanja o ovoj bolesti, kao i novi dijagnostički kriteriji trebali pomoći u njezinu ranom otkrivanju i liječenju, a možda u nekoj bližoj budućnosti i njezinoj eradikaciji.
Even though the endocrine-disrupting potential of perfluorooctanoic acid (PFOA) is well known, the mechanisms underlying its cellular and epigenetic toxicity at the critical stage of hypothalamic ...development are poorly understood. This is why we studied its effects on the embryonic mouse hypothalamic cell line N46 (mHypoE-N46) with a hope to shed more light on the mechanisms through which PFOA causes embryonic hypothalamic cell damage. To do that, we studied cell viability, global DNA methylation, and gene expression in cells exposed to PFOA. As the PFOA dose increased, cell viability decreased, while global DNA methylation increased. PFOA also significantly altered the expression of genes related to the apoptosis and cell cycle, neurotrophic genes, and the
,
, and
genes. Our findings suggest that exposure to PFOA affects cell survival through the reprogramming of embryonic hypothalamic DNA methylation patterns and altering cell homeostasis genes. DNA methylation and changes in the
gene expression induced by PFOA also imply wider ramifications, as they alter genes of other major mechanisms of the embryonic hypothalamus. Our study may therefore serve as a good starting point for further research into the mechanisms of PFOA effect of hypothalamic development.
The inability of standard therapy to provide adequate protection against poisoning by organophosphorus compounds (pesticides and nerve agents) motivated us to search for new, more effective oximes. ...We investigated the pharmacotoxicological properties of six experimental K-oximes (K027, K033, K048, K074, K075, and K203) in vivo. The therapeutic efficacy of K-oximes (at doses of 5 or 25 % of their LD
) combined with atropine was assessed in paraoxon-poisoned mice and compared with conventionally used oximes HI-6 and TMB-4. The bisoxime K074 was the most toxic (LD
=21.4 mg kg
) to mice, while monoxime K027 was the least toxic (LD
=672.8 mg kg
). With the exception of K033, all of the tested K-oximes showed better therapeutic efficiency than HI-6 and TMB-4. K027 and K048 stood out by demonstrating low acute toxicities and ensuring protective indices ranging from 60.0 to 100.0 LD
of paraoxon. Taking into account that these two oximes showed a similar therapeutic efficacy regardless of the applied doses, our results suggest that K027 and K048 could be antidotes for paraoxon intoxication.
Činjenica da standardna terapija ne omogućuje dovoljnu zaštitu pri otrovanju organofosfornim spojevima (pesticidima i živčanim bojnim otrovima) potaknula nas je na istraživanje novih, učinkovitijih oksima. U uvjetima in vivo ispitali smo farmakotoksikološka svojstva šest eksperimentalnih K-oksima (K027, K033, K048, K074, K075 i K203). Terapijski učinak kombinacije K-oksima (primjenjenih u dozi 5 ili 25 % njihove LD50) i atropina testiran je na miševima otrovanim paraoksonom i uspoređen s konvencionalnim oksimima HI-6 i TMB-4. Bisoksim K074 je bio najtoksičniji (LD
=21.4 mg kg
) za miševe, dok je monooksim K027 bio najmanje toksičan (LD
=672.8 mg kg
). Osim K033, svi K-oksimi pokazali su bolji terapijski učinak u miševa trovanih paraoksonom u odnosu na HI-6 i TMB-4. Iz skupine testiranih oksima istaknuli su se K027 i K048 koji su pokazali nisku akutnu toksičnost i osigurali protektivne indekse u rasponu od 60.0 do 100.0 LD50 paraoksona. Uzmemo li u obzir da su ta dva oksima pokazala sličan terapijski učinak bez obzira na primjenjenu dozu, prikazani rezultati upućuju na K027 i K048 kao perspektivne antidote u terapiji trovanja paraoksonom.
Maligni pleuralni mezoteliom rijetka je i agresivna primarna novotvorina mezotelnih stanica pleure. Glavni rizični čimbenik je izloženost azbestu, najčešće uz latenciju od 30–50 godina. Unatoč ...terapiji medijan preživljenja je od 4 do 18 mjeseci, ovisno o izvoru. Cilj istraživanja bio je odrediti karakteristike bolesnika oboljelih od malignoga pleuralnog mezotelioma te ishode njihova liječenja na KBC Zagreb u razdoblju od 1999. do 2012. godine. Ispitane su karakteristike 101 bolesnika dijagnosticiranog i liječenog na KBC Zagreb u razdoblju od rujna 1999. do rujna 2012. Analizirali smo ukupno preživljenje (OS), preživljenje bez progresije bolesti (PFS) te preživljenje ovisno o histološkom podtipu tumora, dobi, kliničkom stadiju, pleurodezi talkom i modalitetu liječenja. Koristili smo Kaplan-Meierovu metodu za izradu krivulje preživljenja. 89 bolesnika bilo je muškog, 12 ženskog spola, a medijan dobi 62 godine. Prema TNM klasifikaciji stadij IV je utvrđen kod 69,3%, stadij III kod 26,73%, te stadij II kod samo 3,96% bolesnika. 73,26% bolesnika imalo je epiteloidni, 4,95% sarkomatoidni, 1% mješoviti te 20,79% NOS (nespecifirani) histološki podtip bolesti. Kirurški je liječeno 14,85% bolesnika, kemoterapijom 55,44%, dok je radioterapija primijenjena kod 9,9% bolesnika. Medijan OS iznosi 11 mjeseci, dok je PFS 10 mjeseci. Prema histološkom podtipu medijan OS iznosio je 11 mjeseci za epiteloidni, 12,5 za NOS te 5,5 za sarkomatoidni, a prema kliničkom stadiju 7 mjeseci za stadij II, 17,5 mjeseci za stadij III te 11 mjeseci za stadij IV. Medijan OS bio je dulji u skupini bolesnika mlađoj od 65 godina (12 naspram 8,5 mjeseci, p=0.28), skupini sa učinjenom pleurodezom (13 naspram 7,5 mjeseci, p=0.06) te u skupini liječenoj kemoterapijom (12,5 naspram 7,5 mjeseci, p=0.10). Očekivano preživljenje bolesnika oboljelih od malignoga pleuralnog mezotelioma u Republici Hrvatskoj u skladu je s podatcima iz literature. Ispitane metode liječenja relativno skromno utječu na preživljenje bolesnika.
This study aimed to investigate the effect of 150 mg/L sodium fluoride (NaF) on redox status parameters and essential metals copper (Cu), iron (Fe), and zinc (Zn) in the blood, liver, kidney, brain, ...and spleen of Wistar rats and to determine the protective potential of selenium (Se) against fluoride (F
) toxicity. Male Wistar rats were randomly distributed in groups of five (n=5) receiving tap water (control) or water with NaF 150 mg/L, NaF 150 mg/L + Se 1.5 mg/L, and Se 1.5 mg/L solutions
for 28 days. Fluorides caused an imbalance in the redox and biometal (Cu, Fe, and Zn) status, leading to high superoxide anion (O
) and malondialdehyde (MDA) levels in the blood and brain and a drop in superoxide dismutase (SOD1) activity in the liver and its increase in the brain and kidneys. Se given with NaF improved MDA, SOD1, and O
in the blood, brain, and kidneys, while alone it decreased SH group levels in the liver and kidney. Biometals both reduced and increased F- toxicity. Further research is needed before Se should be considered as a promising strategy for mitigating F
toxicity.
Lysergic acid diethylamide (LSD) is a classic hallucinogen, widely abused for decades, while phencyclidine (PCP) has increased in popularity in recent years, especially among the adolescents. Very ...little is known about the general toxicity of these compounds, especially about their possible neurotoxic effects at the cell level. The aim of this study was to address these gaps by assessing the toxic effects of 24-hour exposure to LSD and PCP in the concentration range of 0.39–100 μmol/L in the human neuroblastoma SH-SY5Y cell line. After cell viability was established, cells treated with concentrations that reduced their viability up to 30 % were further subjected to the alkaline comet assay and biochemical assays that enable estimation of oxidative stress-related effects. Treatment with LSD at 6.25 μmol/L and with PCP at 3.13 μmol/L resulted with 88.06±2.05 and 84.17±3.19 % of viable cells, respectively, and led to a significant increase in primary DNA damage compared to negative control. LSD also caused a significant increase in malondialdehyde level, reactive oxygen species (ROS) production, and glutathione (GSH) level, PCP significantly increased ROS but lowered GSH compared to control. Treatment with LSD significantly increased the activities of all antioxidant enzymes, while PCP treatment significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) but decreased catalase (CAT) activity compared to control. Our findings suggest that LSD has a greater DNA damaging potential and stronger oxidative activity than PCP in SH-SY5Y cells.
Exposure to environmental particulate matter (PM), outdoor air pollution in particular, has long been associated with adverse health effects. Today, PM has widely been accepted as a systemic toxicant ...showing adverse effects beyond the lungs. There are numerous studies, from those
to epidemiological ones, suggesting various direct and indirect PM toxicity mechanisms associated with cardiovascular risks, including inflammatory responses, oxidative stress, changes in blood pressure, autonomic regulation of heart rate, suppression of endothelium-dependent vasodilation, thrombogenesis, myocardial infarction, and fibrinolysis. In addition to these and other health risks, considerations about air quality standards should include individual differences, lifestyle, and vulnerable populations such as children. Urban air pollution has been a major environmental issue for Turkey, and this review will also address current situation, research, and measures taken in our country.
Lead blast furnace slag (LBFS) generated during lead smelting is a hazardous solid waste containing potentially toxic elements (Pb, Zn, As, and Cd) with high mobility and solubility. In this study, a ...process for the utilization of LBFS by carbothermic reduction-magnetic separation method is proposed. Leaching toxicity and Tessier sequential extraction experiments were conducted on LBFS and magnetic separation tailings (TS), and the environmental risk was evaluated using the risk assessment coding index and potential ecological risk index. The obtained results showed that the potentially toxic elements in the TS were solidified in the spinel phase or silicate phase. In addition, the XRD, SEM-EDS, and FTIR results showed the formation of PbCa2Si3O9, ZnAl2O4, and Ca3(AsO4)2 phases. The leaching concentrations of Pb, Zn, As, and Cd in TS were much lower than the toxicity characteristic leaching procedure (TCLP) and China standard leaching test (CSLT) limits. The results of Tessier sequential extraction procedure confirmed that the proportions of the stable residual state of the potentially toxic elements in TS were significantly higher than in LBFS. Furthermore, the ecological environmental risk level for the TS decreased significantly compared to that of LBFS.
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