Search

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., Okratoksin A(OTA) i citrinin (CTN) nefrotoksični su mikotoksini koji zajednički kontaminiraju žitarice. Cilj ovoga istraživanja bio je izmjeriti koncentraciju OTA-e i CTN-a u bubrezima i jetri štakora, tretiranih tim mikotoksinima, te provjeriti hoće li tretman resveratrolom (RSV) smanjiti koncentraciju mikotoksina u tkivima. Istraživanje je provedeno na mužjacima štakora soja Wistar, koji su 21 dan bili tretirani OTA-om (0,125 i 0,250 mg/kg t. m.), a dva dana CTN-om (20 mg/kg t. m.) ili kombinacijama tih mikotoksina. Dvije skupine štakora koje su tretirane mikotoksinima OTA+CTN dobivale su 21 dan RSV (20 mg/kg t. m.). Povećanje koncentracija OTA-e u bubrezima i jetri bio je u skladu s povećanjem doze. Tretman mikotoksinima OTA+CTN smanjio je nakupljanje OTA-e u bubrezima i jetri, a povećao je koncentraciju CTN-a. Tretman RSV-om povećao je koncentraciju OTA-e u bubrezima i jetri, ali je smanjio koncentraciju CTN-a u bubrezima tretiranih štakora. Koncentracija OTA-e značajno se smanjila u prisutnosti CTN-a, vjerojatno zbog kompeticije CTN-a i OTA-e za prijenosnike OAT1 i 3, koji služe za prijenos tih toksina kroz membrane u bubrezima.

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., Dietilamid lizerginske kiseline (LSD) klasični je halucinogen koji se desetljećima naširoko zlorabio, dok je posljednjih godina porasla popularnost fenciklidina (PCP), osobito među adolescentima. Do sada se vrlo malo zna o općoj toksičnosti ovih spojeva, posebice o njihovim mogućim neurotoksičnim učincima na staničnoj razini. Ovo istraživanje procijenilo je toksične učinke LSD-a i PCP-a na staničnu liniju humanoga neuroblastoma SH-SY5Y, koja je bila izložena ispitivanim spojevima u rasponu koncentracija 0,39–100 µmol/L tijekom 24 sata. Stanice tretirane odabranim koncentracijama koje su smanjile vijabilnost stanica do 30 % potom su podvrgnute alkalnom komet-testu i biokemijskim testovima koji omogućuju procjenu oksidacijskoga stresa. Tretman s LSD-om od 6,25 µmol/L i PCP-om s 3,13 µmol/L rezultirao je s 88,06±2,05 % odnosno 84,17±3,19 % vijabilnih stanica. Ove koncentracije omogućile su ispitivanje genotoksičnosti, što je rezultiralo značajnim povećanjem primarnog oštećenja DNA nakon tretmana LSD-om i PCP-om u odnosu na negativnu kontrolu. LSD je izazvao značajno povećanje razine malondialdehida u usporedbi s kontrolom, za razliku od PCP-a. Dok je LSD inducirao značajno povećanje proizvodnje reaktivnih kisikovih vrsta (ROS) i razine glutationa (GSH), tretman PCP-om uzrokovao je značajno povećanje proizvodnje ROS-a, ali smanjenje razine GSH-a u usporedbi s kontrolom. Tretman stanica LSD-om značajno je povećao aktivnosti svih antioksidacijskih enzima u usporedbi s kontrolom. Tretman PCP-om značajno je povećao aktivnosti glutation peroksidaze (GPx) i superoksid dismutaze (SOD), ali je aktivnost katalaze (CAT) bila značajno niža nego u odgovarajućoj kontroli. Zaključno, LSD je imao veći potencijal oštećenja DNA i pokazao je jaču oksidacijsku aktivnost od PCP-a u stanicama SH-SY5Y.

Toxic metals are extensively found in the environment, households, and workplaces and contaminate food and drinking water. The crosstalk between environmental exposure to toxic metals and human diseases has been frequently described. The toxic mechanism of action was classically viewed as the ability to dysregulate the redox status, production of inflammatory mediators and alteration of mitochondrial function. Recently, growing evidence showed that heavy metals might exert their toxicity through microRNAs (miRNA)-short, single-stranded, noncoding molecules that function as positive/negative regulators of gene expression. Aberrant alteration of the endogenous miRNA has been directly implicated in various pathophysiological conditions and signaling pathways, consequently leading to different types of cancer and human diseases. Additionally, the gene-regulatory capacity of miRNAs is particularly valuable in the brain-a complex organ with neurons demonstrating a significant ability to adapt following environmental stimuli. Accordingly, dysregulated miRNAs identified in patients suffering from neurological diseases might serve as biomarkers for the earlier diagnosis and monitoring of disease progression. This review will greatly emphasize the effect of the toxic metals on human miRNA activities and how this contributes to progression of diseases such as cancer and neurodegenerative disorders (NDDs).