Urbanizacija i industrijalizacija su u porastu u cijelome svijetu. S obama ovim fenomenima izravno su povezana zagađivala iz okoliša, poput
potencijalno toksičnih elemenata (PTE). Dva elementa koja ...izazivaju najveću zabrinutost su arsen (As) i olovo (Pb) u tlu i vodi, bilo da su
tamo došli prirodnim putem ili zbog ljudske djelatnosti. Oba su i potencijalno kancerogena. U ovom preglednom radu razmatraju se
mehanizmi kojima As i Pb ugrožavaju metaboličke procese i izazivaju oštećenja genoma. Unatoč zabranama i naporima da se ograniči
njihovo korištenje, oba su elementa perzistentna u okolišu i predstavljaju rizik za ljudsko zdravlje, zbog čega je potrebno nastaviti s njihovim
toksikološkim istraživanjima.
Recent research has raised concern about the biocompatibility of iron oxide nanoparticles (IONPs), as they have been reported to induce oxidative stress and inflammatory responses, whilst prolonged ...exposure to high IONP concentrations may lead to cyto-/genotoxicity. Besides, there is concern about its environmental impact. The aim of our study was to investigate the effects of IONPs on the antioxidant defence system in freshwater fish Mozambique tilapia (
Peters 1852). The fish were exposed to IONP concentration of 15 mg/L over 1, 3, 4, 15, 30, and 60 days and the findings compared to a control, unexposed group. In addition, we followed up the fish for 60 days after exposure had stopped to estimate the stability of oxidative stress induced by IONPs. Exposure affected the activity of antioxidant and marker enzymes and increased the levels of hydrogen peroxide and lipid peroxidation in the gill, liver, and brain tissues of the fish. Even after 60 days of depuration, adverse effects remained, indicating long-term nanotoxicity. Moreover, IONPs accumulated in the gill, liver, and brain tissues. Our findings underscore the potential health risks posed to non-target organisms in the environment, and it is imperative to establish appropriate guidelines for safe handling and disposal of IONPs to protect the aquatic environment.
Valproate is known to disturb the kidney function, and high doses or prolonged intake may cause serum ion imbalance, kidney tubular acidosis, proteinuria, hyperuricosuria, polyuria, polydipsia, and ...dehydration. The aim of this
study was to see whether naringin would counter the adverse effects of high-dose valproate in C57Bl/6 mice and to which extent. As expected, valproate (150 mg/kg bw a day for 10 days) caused serum hyperkalaemia, more in male than female mice. Naringin reversed (25 mg/kg bw a day for 10 days) the hyperkalaemia and activated antioxidative defence mechanisms (mainly catalase and glutathione), again more efficiently in females. In males naringin combined with valproate was not as effective and even showed some prooxidative effects.
Most Pb and Cd neurotoxicity studies investigate exposure to either of the toxic metals alone, while data on co-exposure are scarce. The aim of our study was to fill that gap by investigating acute ...combined effects of Pb and Cd on redox and essential metal status in the brain of Wistar rats. Animals were randomised in four groups of six to eight rats, which received 15 or 30 mg/kg of Cd, 150 mg/kg of Pb, or 150 mg/kg of Pb + 15 mg/kg of Cd by gavage. The fifth, control, group received distilled water only. Co-treatment with Pb and Cd induced significant increase in malondialdehyde (MDA) and thiobarbituric acid-reactive substances (TBARS) compared to control and groups receiving either metal alone. This is of special importance, as MDA presence in the brain has been implicated in many neurodegenerative disorders. The groups did not significantly differ in Zn, Cu, Mn, and Fe brain levels. Our findings highlight the importance of metal mixture studies. Neurotoxicity assessments of single chemicals do not provide a real insight into exposure to mixtures in real life. Further research should look into interactions between these metals to reveal complex molecular mechanisms of their neurotoxicity.
Clinical treatment with the antineoplastic drug irinotecan (IRI) is often hindered by side effects that significantly reduce the quality of life of treated patients. Due to the growing public support ...for products with Δ
-tetrahydrocannabinol (THC), even though relevant scientific literature does not provide clear evidence of their high antitumour potential, some cancer patients take unregistered preparations containing up to 80 % THC. This study was conducted on a syngeneic colorectal cancer mouse model to test the efficiency and safety of concomitant treatment with IRI and THC. Male BALB/c mice subcutaneously injected with CT26 cells were receiving 60 mg/kg of IRI intraperitoneally on day 1 and 5 of treatment and/or 7 mg/kg of THC by gavage a day for 7 days. Treatment responses were evaluated based on changes in body, brain, and liver weight, tumour growth, blood cholinesterase activity, and oxidative stress parameters. Irinotecan’s systemic toxicity was evidenced by weight loss and high oxidative stress. The important finding of this study is that combining THC with IRI diminishes IRI efficiency in inhibiting tumour growth. However, further studies, focused on more subtle molecular methods in tumour tissue and analytical analysis of IRI and THC distribution in tumour-bearing mice, are needed to prove our observations.
The aim of this study was to investigate the effects of resveratrol against fumonisin B
(FB
)-induced liver toxicity, as, to the best of our knowledge, these effects have not been investigated yet, ...even though the toxic effects and mechanisms of FB
and the antioxidative effects of resveratrol are well known. 40 BALB/c mice were divided into control, FB
, resveratrol, and FB
+resveratrol groups. Control received saline for 14 days. The FB
group received 2.25 mg/kg FB
every other day for 14 days. The resveratrol group received 10 mg/kg resveratrol for 14 days. The FB
+resveratrol group received 2.25 mg/kg FB
every other day and 10 mg/kg resveratrol every day for 14 days. All administrations were peritoneal. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total sialic acid (TSA) levels were analysed in serum samples, while total antioxidant status (TAS) and total oxidant status (TOS) were measured in the liver. Additionally, the liver tissue was examined for histopathological changes. AST, ALT, and TSA were significantly higher in the FB
group than control. Resveratrol countered FB
effects for all parameters, including TOS and TAS. Liver histology showed FB
-induced hyperaemia, infiltrations, and megalokaryosis in some hepatocytes. No pathological findings were detected in the control, resveratrol, or FB
+resveratrol group. Our findings confirm resveratrol’s protective effect against liver damage and oxidative stress caused by FB
. In addition, they suggest that increased serum TSA levels can be used as a biomarker of FB
-induced hepatotoxicity.
Urbanisation and industrialisation are on the rise all over the world. Environmental contaminants such as potentially toxic elements (PTEs) are directly linked with both phenomena. Two PTEs that ...raise greatest concern are arsenic (As) and lead (Pb) as soil and drinking water contaminants, whether they are naturally occurring or the consequence of human activities. Both elements are potential carcinogens. This paper reviews the mechanisms by which As and Pb impair metabolic processes and cause genetic damage in humans. Despite efforts to ban or limit their use, due to high persistence both continue to pose a risk to human health, which justifies the need for further toxicological research.
Toxicological Properties of Citrinin Flajs, Dubravka (Institute for Medical Research and Occupational Health, Zagreb, Croatia); Peraica, Maja (Institute for Medical Research and Occupational Health, Zagreb, Croatia)
Arhiv za higijenu rada i toksikologiju,
12/2009, Letnik:
60, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Citrinin (CTN) is a nephrotoxic mycotoxin produced by several fungal strains belonging to the genera Penicillium, Aspergillus, and Monascus. It contaminates various commodities of plant origin, ...cereals in particular, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A (OTA). These two mycotoxins are believed to be involved in the aetiology of endemic nephropathy. In addition to nephrotoxicity, CTN is also embryocidal and fetotoxic. The genotoxic properties of CTN have been demonstrated with the micronuleus test (MN), but not with single-cell gel electrophoresis. The mechanism of CTN toxicity is not fully understood, especially not whether CTN toxicity and genotoxicity are the consequence of oxidative stress or of increased permeability of mitochondrial membranes. CTN requires complex cellular biotransformation to exert mutagenicity.Compared with other mycotoxins, CTN contamination of food and feed is rather scarce. However, it is reasonable to believe that humans are much more frequently exposed to CTN than generally accepted, because it is produced by the same moulds as OTA, which is a common contaminant of human food all over the world.At present, there are no specific regulations either in Croatia or in the European Union concerning CTN in any kind of commodity.
Citrinin (CTN) nefrotoksi _an je mikotoksin koji proizvode razli _iti sojevi plijesni iz rodova Penicillium, Aspergillus i Monascus. CTN se može naći u razli _itim namirnicama biljnog podrijetla, osobito u žitaricama i obi _no se nalazi zajedno s drugim nefrotoksi _nim mikotoksinom, okratoksinom A (OTA). Pretpostavlja se da je izloženost ovim mikotoksinima povezana s nastankom endemske nefropatije. Osim što je nefrotoksi _an, CTN je još i embricidan i fetotoksi _an. Na genotoksi _nost citrinina upućuje pozitivan mikronukleusni test na razli _itim vrstama stani _nih kultura, iako je kometski test negativan. Mutagenost CTN-a o _ituje se na razli _itim vrstama stanica samo ako se pridodaju stani _ni aktivatori kao npr. S9-mix. Mehanizam toksi _nosti CTN-a nije potpuno razjašnjen pa još uvijek traje znanstvena rasprava je li njegova toksi _nost i genotoksi _nost posljedica oksidacijskog stresa ili povećane permeabilnosti mitohondrijskih membrana. U dostupnoj literaturi podaci o kontaminiranosti hrane i krmiva ovim mikotoksinom mnogo su rjeđi od onih za druge mikotoksine. Može se pretpostaviti da su ljudi _esto izloženi ovom mikotoksinu zato što ga proizvode iste plijesni koje proizvode i OTA, a one kontaminiraju hranu po cijelom svijetu.U Hrvatskoj i u zemljama Europske Unije ne postoje zakonske odredbe o dopuštenim granicama CTN-a u bilo kojoj vrsti hrane.
The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue ...of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains.
Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls, exerts hepatic, renal, and reproductive toxicity in rodents. This study aimed to determine a protective role of selenium on ...histopathological changes, oxidative stress, and apoptosis caused by A1254 in rat kidney. It included a control group, which received regular diet containing 0.15 mg/kg Se (C), a Se-supplemented group (SeS) receiving 1 mg/kg Se, a Se-deficient group (SeD) receiving Se-deficient diet of ≤0.05 mg/kg Se, an A1254-treated group (A) receiving 10 mg/kg of Aroclor 1254 and regular diet, an A1254-treated group receiving Se-supplementation (ASeS), and an A1254-treated group receiving Se-deficient diet (ASeD). Treatments lasted 15 days. After 24 h of the last dose of A1254, the animals were decapitated under anaesthesia and their renal antioxidant enzyme activities, lipid peroxidation (LP), glutathione, protein oxidation, and total antioxidant capacity levels measured. Histopathological changes were evaluated by light and electron microscopy. Apoptosis was detected with the TUNEL assay. Kidney weights, CAT activities, and GSH levels decreased significantly in all A1254-treated groups. Renal atrophic changes and higher apoptotic cell counts were observed in the A and ASeD groups. Both groups also showed a significant drop in GPx1 activities (A – 34.92 % and ASeD – 86.46 %) and rise in LP (A – 30.45 % and ASeD – 20.44 %) vs control. In contrast, LP levels and apoptotic cell counts were significantly lower in the ASeS group vs the A group. Histopathological changes and renal apoptosis were particularly visible in the ASeD group. Our findings suggest that selenium supplementation provides partial protection against renal toxicity of Aroclor 1254.
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