Archives of Industrial Hygiene and Toxicology

Untying the anchor for the lipopolysaccharide: lipid A structural modification systems offer diagnostic and therapeutic options to tackle polymyxin resistance

Vanessa Rogga, Ivan Kosalec — Mon, 28 Aug 2023 12:38:28 +0200

Polymyxin antibiotics are the last resort for treating patients in intensive care units infected with multiple-resistant Gram-negative bacteria. Due to their polycationic structure, their mode of action is based on an ionic interaction with the negatively charged lipid A portion of the lipopolysaccharide (LPS). The most prevalent polymyxin resistance mechanisms involve covalent modifications of lipid A: addition of the cationic sugar 4-amino-L-arabinose (L-Ara4N) and/or phosphoethanolamine (pEtN). The modified structure of lipid A has a lower net negative charge, leading to the repulsion of polymyxins and bacterial resistance to membrane disruption. Genes encoding the enzymatic systems involved in these modifications can be transferred either through chromosomes or mobile genetic elements. Therefore, new approaches to resistance diagnostics have been developed. On another note, interfering with these enzymatic systems might offer new therapeutic targets for drug discovery. This literature review focuses on diagnostic approaches based on structural changes in lipid A and on the therapeutic potential of molecules interfering with these changes.

The effects of per- and polyfluoroalkyl substances on environmental and human microorganisms and their potential for bioremediation

Mon, 21 Aug 2023 13:30:30 +0200

Utilised in a variety of consumer products, per- and polyfluoroalkyl substances (PFAS) are major environmental contaminants that accumulate in living organisms due to their highly hydrophobic, lipophobic, heat-resistant, and non-biodegradable properties. This review summarizes their effects on microbial populations in soils, aquatic and biogeochemical systems, and the human microbiome. Specific microbes are insensitive to and even thrive with PFAS contamination, such as Escherichia coli and the Proteobacteria in soil and aquatic environments, while some bacterial species, such as Actinobacteria and Chloroflexi, are sensitive and drop in population. Some bacterial species, in turn, have shown success in PFAS bioremediation, such as Acidimicrobium sp. and Pseudomonas parafulva.

Exploring the link between sulphur-containing compounds and noxious odours at waste management facilities: implications for odour monitoring and mitigation strategies

Mon, 28 Aug 2023 12:42:29 +0200

With this study we challenge the widely held assumption that the concentration of sulphur-containing compounds in ambient air is a good indicator of noxious odours. To do that, we analysed an extensive set of olfactometric data and data obtained from the concentration measurements of hydrogen sulphide and trace sulphur compounds (TSCs) conducted near a waste management facility in Croatia in 2021. The results show that variation in odour nuisance can be explained only by hydrogen sulphide and methyl mercaptan content in ambient air, for which we found a statistically significant correlation, but not for TSCs, including ethyl mercaptan, methyl sulphide, dimethyl sulphide, and dimethyl disulphide. In other words, only hydrogen and methyl mercaptan can be used as a proxy for measuring noxious odours. As for other TSCs, olfactometric analyses of noxious odours should follow the limits set by the Integrated Pollution and Prevention Control (IPPC) permits when waste management facilities are concerned.

Evaluation of the risk of occupational exposure to antineoplastic drugs in healthcare sector: part I – medical gloves

Wed, 02 Aug 2023 11:30:16 +0200

Antineoplastic drugs (ADs) are essential tools in cancer treatment, but their cytotoxicity poses a risk to workers involved in their handling. In a hospital environment fundamental strategies for minimising exposure involve proper use of safety cabinets and closed-circuit transfer devices, along with personnel training and increased awareness of risks. However, medical gloves remain the first line of defence. In this respect the evaluation of glove materials and best choices can improve hospital safety management and prevent potential hazards and long-term consequences. The aim of this study was to assess contamination of gloves in samples taken from AD administration and preparation units of nine Italian hospitals and to raise awareness of the importance of evaluating chemico-physical properties of gloves. Our findings show that 33 % of the analysed gloves were positive for at least one AD, with contaminations ranging from 0.6 to 20,729 pg/cm². We proposed the alert glove values (AGVs) for each AD as a limit value for contamination assessment and good practice evaluation. Our findings also point to multiple AD contamination (43 % of positive findings in preparation units), calculated as total AGV (AGV-T), and confirm that gloves should be replaced after 30 min of AD handling, based on cumulative permeation and area under the curve (AUC), to maintain safety and limit dermal exposure.

Effects of concomitant use of THC and irinotecan on tumour growth and biochemical markers in a syngeneic mouse model of colon cancer

Tue, 19 Sep 2023 14:25:34 +0200

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 Δ⁹-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.

L-glutamic acid-g-poly hydroxyethyl methacrylate nanoparticles: acute and sub-acute toxicity and biodistribution potential in mice

Wed, 13 Sep 2023 11:56:21 +0200

The aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD₅₀ was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS spectrum. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.

Combined effects of valproate and naringin on kidney antioxidative markers and serum parameters of kidney function in C57BL6 mice

Mon, 25 Sep 2023 11:01:43 +0200

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 in vivo 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.