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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., (© 2023 Andreja Jurič et al., published by Sciendo.)

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., (© 2022 Dubravka Rašić, Srđan Stefanović, Dragan Milićević, Marin Mladinić, Davor Želježić, Alica Pizent, Paško Konjevoda, Maja Peraica, published by Sciendo.)

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., (© 2021 Heinz-Elmar Tenorth, published by Sciendo.)

Manufacture of lead-containing products has long been associated with various health risks. To get an insight into the related genotoxic risks, we conducted a biomonitoring study in 50 exposed workers and 48 matched controls using a battery of endpoints that sensitively detect the extent of genome instability in peripheral blood lymphocytes. The levels of primary DNA damage were estimated with the alkaline comet assay, while cytogenetic abnormalities were determined with the cytokinesis-block micronucleus (CBMN) cytome assay. Additionally, CBMN slides of 20 exposed and 16 control participants were subjected to fluorescence in situ hybridisation (FISH), coupled with pancentromeric probes to establish the incidence of centromere-positive micronuclei, nuclear buds, and nucleoplasmic bridges. Blood lead levels (B-Pb) were measured with atomic absorption spectrometry. To further characterise cumulative effects of occupational exposure, we measured erythrocyte protoporphyrin (EP) concentrations and delta-aminolevulinic acid dehydratase (ALAD) activity in blood. We also assessed the influence of serum folate (S-folate) and vitamin B12 (S-B12) on genome stability. Compared to controls, occupationally exposed workers demonstrated significantly higher B-Pb (298.36±162.07 vs 41.58±23.02), MN frequency (18.71±11.06 vs 8.98±7.50), centromere positive MN (C+ MN) (8.15±1.8 vs 3.69±0.47), and centromere negative MN (C- MN) (14.55±1.80 vs 4.56±0.89). Exposed women had significantly higher comet tail intensity (TI) and length (TL) than control women. Furthermore, workers showed a positive correlation between age and nuclear buds and MN, between MN and years of exposure, and between S-B12 levels and TI and ALAD activity, while a negative correlation was found between TI and B-Pb. These findings suggest that occupational settings in the manufacture of lead-containing products pose significant genotoxic risks, which calls for developing more effective work safety programmes, including periodical monitoring of B-Pb and genetic endpoints.

This review article provides a summary of the studies relying on oxidative stress biomarkers (lipid peroxidation and antioxidant enzymes in particular) to investigate the effects of atrazine and terbuthylazine exposure in experimental animals and humans published since 2010. In general, experimental animals showed that atrazine and terbuthylazine exposure mostly affected their antioxidant defences and, to a lesser extent, lipid peroxidation, but the effects varied by the species, sex, age, herbicide concentration, and duration of exposure. Most of the studies involved aquatic organisms as useful and sensitive bio-indicators of environmental pollution and important part of the food chain. In laboratory mice and rats changes in oxidative stress markers were visible only with exposure to high doses of atrazine. Recently, our group reported that low-dose terbuthylazine could also induce oxidative stress in Wistar rats. It is evident that any experimental assessment of pesticide toxic effects should take into account a combination of several oxidative stress and antioxidant defence biomarkers in various tissues and cell compartments. The identified effects in experimental models should then be complemented and validated by epidemiological studies. This is important if we wish to understand the impact of pesticides on human health and to establish safe limits.

In this 28 day-study, we evaluated the effects of herbicide glyphosate administered by gavage to Wistar rats at daily doses equivalent to 0.1 of the acceptable operator exposure level (AOEL), 0.5 of the consumer acceptable daily intake (ADI), 1.75 (corresponding to the chronic population-adjusted dose, cPAD), and 10 mg kg-1 body weight (bw) (corresponding to 100 times the AOEL). At the end of each treatment, the body and liver weights were measured and compared with their baseline values. DNA damage in leukocytes and liver tissue was estimated with the alkaline comet assay. Oxidative stress was evaluated using a battery of endpoints to establish lipid peroxidation via thiobarbituric reactive substances (TBARS) level, level of reactive oxygen species (ROS), glutathione (GSH) level, and the activity of glutathione peroxidase (GSH-Px). Total cholinesterase activity and the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were also measured. The exposed animals gained less weight than control. Treatment resulted in significantly higher primary DNA damage in the liver cells and leukocytes. Glyphosate exposure significantly lowered TBARS in the liver of the AOEL, ADI, and cPAD groups, and in plasma in the AOEL and cPAD group. AChE was inhibited with all treatments, but the AOEL and ADI groups significantly differed from control. Total ChE and plasma/liver ROS/GSH levels did not significantly differ from control, except for the 35 % decrease in ChE in the AOEL and ADI groups and a significant drop in liver GSH in the cPAD and 100xAOEL groups. AOEL and ADI blood GSH-Px activity dropped significantly, but in the liver it significantly increased in the ADI, cPAD, and 100xAOEL groups vs. control. All these findings show that even exposure to low glyphosate levels can have serious adverse effects and points to a need to change the approach to risk assessment of low-level chronic/sub-chronic glyphosate exposure, where oxidative stress is not necessarily related to the genetic damage and AChE inhibition.

A combination of genetic, environmental and lifestyle factors contributes to adverse effects on the reproductive health in men. Metals are pervasive in food, water, air, tobacco smoke, and alcoholic beverages. Experimental studies suggest that many metals have adverse effects on the male reproductive function. However, information about reproductive effects of human exposure to metals is scarce and/or inconsistent. This review summarises the information from epidemiological studies of the effects of metal exposure on reproductive function in men. Factors capable of affecting these relationships were identified and discussed. A particular attention is given to the studies considering influence of concomitant exposure to various metals. These studies have generally confirmed that even moderate- to low-level exposure to lead affects certain reproductive parameters, and that exposure to cadmium affects the prostate function and serum testosterone levels. Adverse effects of mercury, manganese, chromium and arsenic on semen quality and altered serum hormone are less well documented. There is no clear evidence that boron exposure may impair reproductive health in men. Only a few studies have investigated reproductive effects of concomitant exposure to several metals and controlled for potential confounders. Future studies should consider the contribution of combined exposure to various metals and/or other factors that may influence individual susceptibility to reproductive health impairment in men.

To estimate Cu exposure level from wine consumption and to assess possible health risk for moderate wine consumers, wine samples were collected from different wine-growing areas of Croatia. Median concentrations were 180 μg L-1, range (76 to 292) μg L-1, in commercial wines and 258 μg L-1, range (115 to 7600) μg L-1, in homemade wines (P>0.05). Maximum permitted level of 1000 μg L-1 was exceeded in three homemade wines. However, daily intake of Cu from wine (in the range from 0.02 mg d-1 to 1.52 mg d-1) estimated from Cu concentration in all wine samples is lower than the tolerable upper intake level of 5 mg d-1 proposed by the EU Scientific Committee on Food and does not present a risk to moderate wine consumers.

A method has been developed for direct determination of lead in wine by graphite furnace atomic absorption spectrometry (GFAAS) with Zeeman-effect background correction. The thermal behaviour of Pb during pyrolysis and atomisation stages was investigated without matrix modifier and in the presence of Pd(NO(3))(2), Pd(NO(3))(2) + Mg(NO(3))(2) × 6H(2)O, and NH(4)H(2)PO(4) + Mg(NO(3))(2) × 6H(2)O as matrix modifiers. A simple 1:1 dilution of wine samples with Pd(NO3)2 as a matrix modifier proved optimal for accurate determination of Pb in wine. Mean recoveries were 106 % for red and 114 % for white wine, and the detection limit was 3 μg L(-1). Within-run precision of measurements for red and white wine was 2.1 % and 1.8 %, respectively. The proposed method was applied for analysis of 23 Croatian wines. Median Pb concentrations were 33 μg L(-1), range (16 to 49) μg L(-1) in commercially available wines and 46 μg L(-1), range (14 to 559) μg L(-1) in home-made wines. There were no statistically significant differences (P<0.05) in Pb concentration between commercial and home-made wines or between red and white wines.

Copper concentration was estimated in tap water samples obtained from 70 households in Zagreb, serviced by a public water supply system. First-draw and flushed samples of tap water were collected in the morning and total copper concentration was determined by graphite furnace atomic absorption spectrometry with Zeeman-effect background correction. We also estimated the contribution of plumbing material to copper concentrations in tap water. In households with copper pipes, median and range copper values were 310 μg L-1 [(27 to 632) μg L-1] in first-draw samples and 16 μg L-1 [(5 to 52) μg L-1] in flushed samples. Corresponding values for households with galvanised pipes were 140 μg L-1 [(11 to 289) μg L-1] and 8 μg L-1 [(1 to 42) μg L-1], respectively. Copper concentrations in household tap water in Zagreb were far below the proposed safe limits set by the Croatian and WHO regulations and EPA standards, and drinking water in Zagreb is not a significant source of copper exposure.

The combined influence of age, smoking, alcohol, blood lead and cadmium concentrations, and serum copper, zinc, and selenium concentrations on prostate-specific antigen (PSA) in serum was investigated in a group of 57 men aged 21 years to 40 years. The subjects had no occupational exposure to metals and no other known reasons suspected of influencing prostate function or metal metabolism. No significant correlation was found between PSA and any of the explanatory variables considered. Nevertheless, when taking into account all of the above-mentioned potentially explanatory variables, the results of stepwise multiple regression showed a significant increase in PSA with respect to an increase in blood lead, and a decrease in PSA with respect to an increase in intensity of alcohol consumption. The median and range values of blood lead concentration in the 57 men were 26.0 microg L(-1) and (10.1 to 108.0) microg L(-1), respectively. These results suggest that even a low-level environmental lead exposure, common for general populations worldwide, may contribute to the risk of prostate cancer in men. The influence of lead as well as cadmium, zinc, and selenium on prostate damage and PSA should be further investigated in relatively young men for the purpose of disease prevention.