Potential cellular targets of platinum in the freshwater microalgae Chlamydomonas reinhardtii and Nitzschia palea revealed by transcriptomics.

Platinum group element levels have increased in natural aquatic environments in the last few decades, in particular as a consequence of the use of automobile catalytic converters on a global scale. Concentrations of Pt over tens of µg L-1 have been observed in rivers and effluents. This raises questions regarding its possible impacts on aquatic ecosystems, as Pt natural background concentrations are extremely low to undetectable. Primary producers, such as microalgae, are of great ecological importance, as they are at the base of the food web. The purpose of this work was to better understand the impact of Pt on a cellular level for freshwater unicellular algae. Two species with different characteristics, a green alga C. reinhardtii and a diatom N. palea, were studied. The bioaccumulation of Pt as well as its effect on growth were quantified. Moreover, the induction or repression factors of 16 specific genes were determined and allowed for the determination of possible intracellular effects and pathways of Pt. Both species seemed to be experiencing copper deficiency as suggested by inductions of genes linked to copper transporters. This is an indication that Pt might be internalized through the Cu(I) metabolic pathway. Moreover, Pt could possibly be excreted using an efflux pump. Other highlights include a concentration-dependent negative impact of Pt on mitochondrial metabolism for C. reinhardtii which is not observed for N. palea. These findings allowed for a better understanding of some of the possible impacts of Pt on freshwater primary producers, and also lay the foundations for the investigation of pathways for Pt entry at the base of the aquatic food web.

In vitro skin permeation of potassium hexachloroplatinate and a comparison with potassium tetrachloroplatinate.

Halogenated platinum salts are known respiratory sensitizers in the workplace, and occupational exposure to platinum via the respiratory system and skin has been reported. The aim of this study was to compare the permeability and skin retention of potassium hexachloroplatinate to previously published data of potassium tetrachloroplatinate. Experiments were performed using female Caucasian skin and Franz diffusion cells with the application of 0.3 mg Pt/mL in the donor solution for 24-h. After 8-h of exposure, 1.87 ng/cm2 of Pt was detected in the receptor solution with exposure to potassium hexachloroplatinate, whereas 0.47 ng/cm2 was detected with exposure to potassium tetrachloroplatinate. After 24-h of exposure the Pt retention in the skin was 1861.60 ng/cm2 and 1486.32 ng/cm2 with exposure to potassium hexa- and tetrachloroplatinate respectively. The faster rate of Pt permeation from exposure to potassium hexachloroplatinate was confirmed by the flux and permeability coefficient values. The results indicate a higher permeability and skin retention of Pt when exposed to potassium hexachloroplatinate, confirming a higher risk associated with occupational exposure to this platinum compound relative to potassium tetrachloroplatinate.

Biodistribution and Toxicological Effects of Ultra-Small Pt Nanoparticles Deposited on Au Nanorods (Au@Pt NRs) in Mice with Intravenous Injection.

Purpose: Pt-based nanostructures are one of the promising nanomaterials for being used in catalysts, sensors, and therapeutics. However, their impacts on the health and biological systems are not adequately understood yet. Methods: In this work, nanorods composed of ultrasmall platinum (Pt) nanoparticles deposited on the surface and gold nanorod as the core (Au@Pt NRs) were synthesized, and the distribution and toxic effects of Au@Pt NRs were investigated in C57BL/6 mice with intravenous injection by using atomic absorption spectroscopy (AAS), transmission electron microscope (TEM), hematoxylin-eosin (HE) staining and blood cell analyzer. Results: At the time point of Day 1, Day 8 and Day 16 post injection of Au@Pt NRs (6 mg/kg of Pt atom), Au@Pt NRs were mainly accumulated in the liver and spleen. The energy dispersive spectrometer mapping images showed Au@Pt NRs experienced quick corrosion and Au released faster than Pt in the physiological environments. The catalase (CAT) activity in tissues increased slightly in the early stage of the Au@Pt NRs exposure and went down to the normal level. With HE staining, inflammatory cells infiltration could be seen in the tissues, while no significant influences were detected on the blood biochemistry and the function of liver and kidney. Conclusion: In conclusion, intravenously injected Au@Pt NRs mainly distributed in the liver and spleen with comparable levels, and did not exert any significant toxic effects on the organs' function within two weeks; meanwhile, Au@Pt NRs were able to degrade, which indicated acceptable safety to the mice and potentials of biomedical application.

How platinum-induced nephrotoxicity occurs? Machine learning prediction in non-small cell lung cancer patients.

BACKGROUND AND OBJECTIVE: Platinum-induced nephrotoxicity is a severe and unexpected adverse drug reaction that could lead to treatment failure in non-small cell lung cancer patients. Better prediction and management of this nephrotoxicity can increase patient survival. Our study aimed to build up and compare the best machine learning models with clinical and genomic features to predict platinum-induced nephrotoxicity in non-small cell lung cancer patients. METHODS: Clinical and genomic data of patients undergoing platinum chemotherapy at Wan Fang Hospital were collected after they were recruited. Twelve models were established by artificial neural network, logistic regression, random forest, and support vector machine with integrated, clinical, and genomic modes. Grid search and genetic algorithm were applied to construct the fine-tuned model with the best combination of predictive hyperparameters and features. Accuracy, precision, recall, F1 score, and area under the receiver operating characteristic curve were calculated to compare the performance of the 12 models. RESULTS: In total, 118 patients were recruited for this study, among which 28 (23.73%) were experiencing nephrotoxicity. Machine learning models with clinical and genomic features achieved better prediction performances than clinical or genomic features alone. Artificial neural network with clinical and genomic features demonstrated the best predictive outcomes among all 12 models. The average accuracy, precision, recall, F1 score and area under the receiver operating characteristic curve of the artificial neural network with integrated mode were 0.923, 0.950, 0.713, 0.808 and 0.900, respectively. CONCLUSIONS: Machine learning models with clinical and genomic features can be a preliminary tool for oncologists to predict platinum-induced nephrotoxicity and provide preventive strategies in advance.

Role of Organic Cation Transporter 2 in Autophagy Induced by Platinum Derivatives.

The human organic cation transporter 2 (hOCT2) mediates renal and neuronal cellular cisplatin and oxaliplatin uptake, and therefore plays a significant role in the development of side effects associated with these chemotherapeutic drugs. Autophagy is induced by cisplatin and oxaliplatin treatment and is believed to promote cell survival under stressful conditions. We examined in vitro the role of hOCT2 on autophagy induced by cisplatin and oxaliplatin. We also explored the effect of autophagy on toxicities of these platinum derivatives. Our results indicate that autophagy, measured as LC3 II accumulation and reduction in p62 expression level, is induced in response to cisplatin and oxaliplatin in HEK293-hOCT2 but not in wild-type HEK293 cells. Furthermore, inhibition of autophagy is associated with higher toxicity of platinum derivatives, and starvation was found to offer protection against cisplatin-associated toxicity. In conclusion, activation of autophagy could be a potential strategy to protect against unwanted toxicities induced by treatment with platinum derivatives.

TFEB Regulates ATP7B Expression to Promote Platinum Chemoresistance in Human Ovarian Cancer Cells.

ATP7B is a hepato-specific Golgi-located ATPase, which plays a key role in the regulation of copper (Cu) homeostasis and signaling. In response to elevated Cu levels, ATP7B traffics from the Golgi to endo-lysosomal structures, where it sequesters excess copper and further promotes its excretion to the bile at the apical surface of hepatocytes. In addition to liver, high ATP7B expression has been reported in tumors with elevated resistance to platinum (Pt)-based chemotherapy. Chemoresistance to Pt drugs represents the current major obstacle for the treatment of large cohorts of cancer patients. Although the mechanisms underlying Pt-tolerance are still ambiguous, accumulating evidence suggests that lysosomal sequestration of Pt drugs by ion transporters (including ATP7B) might significantly contribute to drug resistance development. In this context, signaling mechanisms regulating the expression of transporters such as ATP7B are of great importance. Considering this notion, we investigated whether ATP7B expression in Pt-resistant cells might be driven by transcription factor EB (TFEB), a master regulator of lysosomal gene transcription. Using resistant ovarian cancer IGROV-CP20 cells, we found that TFEB directly binds to the predicted coordinated lysosomal expression and regulation (CLEAR) sites in the proximal promoter and first intron region of ATP7B upon Pt exposure. This binding accelerates transcription of luciferase reporters containing ATP7B CLEAR regions, while suppression of TFEB inhibits ATP7B expression and stimulates cisplatin toxicity in resistant cells. Thus, these data have uncovered a Pt-dependent transcriptional mechanism that contributes to cancer chemoresistance and might be further explored for therapeutic purposes.

α-Fe2O3@Pt heterostructure particles to enable sonodynamic therapy with self-supplied O2 and imaging-guidance.

Sonodynamic therapy (SDT), presenting spatial and temporal control of ROS generation triggered by ultrasound field, has attracted considerable attention in tumor treatment. However, its therapeutic efficacy is severely hindered by the intrinsic hypoxia of solid tumor and the lack of smart design in material band structure. Here in study, fine α-Fe2O3 nanoparticles armored with Pt nanocrystals (α-Fe2O3@Pt) was investigated as an alternative SDT agent with ingenious bandgap and structural design. The Schottky barrier, due to its unique heterostructure, suppresses the recombination of sono-induced electrons and holes, enabling superior ROS generation. More importantly, the composite nanoparticles may effectively trigger a reoxygenation phenomenon to supply sufficient content of oxygen, favoring the ROS induction under the hypoxic condition and its extra role played for ultrasound imaging. In consequence, α-Fe2O3@Pt appears to enable effective tumor inhibition with imaging guidance, both in vitro and in vivo. This study has therefore demonstrated a highly potential platform for ultrasound-driven tumor theranostic, which may spark a series of further explorations in therapeutic systems with more rational material design.

Speciation of platinum nanoparticles in different cell culture media by HPLC-ICP-TQ-MS and complementary techniques: A contribution to toxicological assays.

Toxicological studies of nanoparticles (NPs) are highly demanded nowadays but they are very challenging. In the in vitro assays, the understanding of the role of cell culture media is crucial to derive a proper interpretation of the toxicological results and to do so, new analytical tools are necessary. In this context, an analytical strategy based on reversed-phase liquid chromatography hyphenated to inductively coupled plasma-triple quadrupole mass spectrometry (HPLC-ICP-TQ-MS) has been developed for the first time for the detection and characterization of both 5 and 30 nm PtNPs, as well as ionic platinum species, in commonly used cell culture media. For this purpose, Dulbecco's Modified Eagle Medium, DMEM-high glucose, DMEM-F12, DMEM 31053-028, and Roswell Park Memorial Institute, RPMI-1640 (supplemented with 10% fetal bovine serum (FBS) and antibiotics) at several incubation times (24, 48, and 96 h at 37 °C) were tested. After a careful optimization and analytical performance, the developed method allows to simultaneously study the oxidation process, leading to the release of ionic species, and the increase in the hydrodynamic volume of PtNPs, probably related to the formation of new biological entities (protein corona). The magnitude of both processes was found to be dependent on the tested cell culture media and incubation times. Dynamic light scattering (DLS) and high-resolution scanning electron microscopy (HR-SEM) were used as complementary techniques to study the important process of both soft and hard protein corona formation. The feasibility of the HPLC-ICP-TQ-MS to get relevant information for toxicological studies has been demonstrated and in light of our results, the influence of the cell culture media on the behavior of PtNPs should not be underestimated.

Implications of kinetically-hindered metals in ecotoxicological studies: Effect of platinum spike aging on its toxicity to Dunaliella salina.

Platinum (Pt) is considered an emerging environmental micro-contaminant due to its increasing use in anthropogenic activities during the past decades. However, there are still important gaps in the understanding of its biogeochemical behavior in the aquatic environment - e.g. its speciation, reactivity and fate - mainly as a result of the analytical challenge of the determination of its typical ultra-trace environmental concentrations. Also, Pt is a kinetically-hindered metal displaying slow reaction kinetics, which has important implications regarding eco-toxicological studies. That is, investigation of its toxicity under laboratory-controlled conditions may therefore require ensuring that equilibrium speciation conditions are reached before starting the experiments. In order to shed further light on this issue, in this study we have monitored the speciation changes during aging of the Pt(IV) spikes in controlled media (seawater) using an UV-Vis spectrophotometry. Platinum toxicity to the green microalgae Dunaliella salina was then compared, using standardized tests, with fresh and aged Pt(IV) spikes at the mg L-1 concentration range. Following 96-hour exposure, ecotoxicological assays consisting in spectrometric measurements of chlorophyll-a concentrations and Effective Concentrations (EC) of Pt resulting in the inhibition of 10% and 50% of algae growth rate were calculated (EC10 and EC50, respectively). Daily monitoring of Pt speciation reflected the transition from PtCl62- (spike) to hydrolyzed species, probably in the form [PtCl3-n(OH)3+n]2-, n = 0-3. Exposure experiments showed that after a short period of aging (10 days), Pt(IV) toxicity increased one order of magnitude compared to freshly spiked media. These results confirm the relevance of considering spike aging to ensure that speciation equilibrium conditions are attained in order to produce environmental realistic eco-toxicological data.

Gold-Platinum Nanodots with High-Peroxidase-like Activity and Photothermal Conversion Efficiency for Antibacterial Therapy.

Combined therapeutic strategies for bacterial infection have attracted worldwide attention owing to their faster and more effective therapy with fewer side effects compared with monotherapy. In this work, gold-platinum nanodots (AuPtNDs) are simply and quickly synthesized by a one-step method. They not only exhibit powerful peroxidase-like activity but also confer a higher affinity for hydrogen peroxide (H2O2), which is 3.4 times that of horseradish peroxidase. Under 808 nm laser irradiation, AuPtNDs also have excellent photothermal conversion efficiency (50.53%) and strong photothermal stability. Excitingly, they can combat bacterial infection through the combination of chemodynamic and photothermal therapy. In vitro antibacterial results show that the combined antibacterial strategy has a broad-spectrum antibacterial property against both Escherichia coli (Gram negative, 97.1%) and Staphylococcus aureus (Gram positive, 99.3%). Animal experiments further show that nanodots can effectively promote the healing of bacterial infection wounds. In addition, owing to good biocompatibility and low toxicity, they are hardly traceable in the main organs of mice, which indicates that they can be well excreted through metabolism. These results reveal the application potential of AuPtNDs as a simple and magic multifunctional nanoparticle in antibacterial therapy and open up new applications for clinical anti-infective therapy in the near future.

Anisotropic Truncated Octahedral Au with Pt Deposition on Arris for Localized Surface Plasmon Resonance-Enhanced Photothermal and Photodynamic Therapy of Osteosarcoma.

The multifunctional combined nanoplatform has a wide application prospect in the synergistic treatment of cancer. Nevertheless, the traditional treatment of phototherapy is limited by the catalytic nanomaterial itself, so the effect is not satisfactory. Here, the arris of the anisotropic truncated octahedral Au (TOh Au) was coated with noble metal Pt to form a spatial separation structure, which enhanced the local surface plasmonic resonance and thus boosted the photocatalytic effect. In this system, the highly efficient photocatalysis provides a strong guarantee for oncotherapy. On the one hand, the structure of arris deposition adequately improves the efficiency of photothermal conversion, which substantially improves the effectiveness of photothermal therapy. On the other hand, in situ oxygen production of Pt ameliorates tumor hypoxia, and through the O2 self-production and sales mode, the growth and development of tumor were inhibited. Meanwhile, under the enhanced photocatalysis, more O2 were produced, which greatly evolved the treatment effect of photodynamic therapy. In the end, the addition of hyaluronic acid can specifically target osteosarcoma cells while improving the retention time and biocompatibility of the material in the body. Thus, the nanocomposite shows superexcellent synergistic enhancement of photothermal conversion efficiency and photodynamic capability in vitro and in vivo, which provides a potential possibility for osteosarcoma cure.

Metal contamination and toxicity of soils and river sediments from the world's largest platinum mining area.

Mining activities in the world's largest platinum mining area in South Africa have resulted in environmental contamination with Pt (e.g., the Hex River's vicinity). The present study compared a Pt mining area with a non-mining area along this river in terms of (1) metal concentrations in different grain size fractions from soils and aquatic sediments; (2) the toxicological potential of aquatic sediments based on the Consensus-Based Sediment Quality Guideline (CBSQG); and (3) the chronic toxicity of aqueous eluates from soils and sediments to Caenorhabditis elegans. Platinum concentrations were higher in the mining area than in the non-mining area. For most metals, the sediment silt and clay fraction contained the highest metal concentrations. Based on the CBSQG, most sampling sites exhibited a high toxicological potential, driven by Cr and Ni. Eluate toxicity testing revealed that C. elegans growth, fertility, and reproduction inhibition were not dependent on mining activities or the CBSQG predictions. Toxicity was instead likely due to Cd, Fe, Mn, Ni, Pt, and Pb. In conclusion, the investigated region is loaded with a high geogenic background resulting in high reproduction inhibition. The mining activities lead to additional environmental metal contamination (particularly Pt), contributing to environmental soil and sediment toxicity.

Oxidative stress cytotoxicity induced by platinum-doped magnesia nanoparticles in cancer cells.

The aim of this study was to prepare, characterize, and determine the in vitro anticancer effects of platinum-doped magnesia (Pt/MgO) nanoparticles. The chemical compositions, functional groups, and size of nanoparticles were determined using X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. Pt/MgO nanoparticles were cuboid and in the nanosize range of 30-50 nm. The cytotoxicity of Pt/MgO nanoparticles was determined via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the human lung and colonic cancer cells (A549 and HT29 respectively) and normal human lung and colonic fibroblasts cells (MRC-5 and CCD-18Co repectively). The Pt/MgO nanoparticles were relatively innocuous to normal cells. Pt/MgO nanoparticles downregulated Bcl-2 and upregulated Bax and p53 tumor suppressor proteins in the cancer cells. Pt/MgO nanoparticles also induced production of reactive oxygen species, decreased cellular glutathione level, and increased lipid peroxidation. Thus, the anticancer effects of Pt/MgO nanoparticles were attributed to the induction of oxidative stress and apoptosis. The study showed the potential of Pt/MgO nanoparticles as an anti-cancer compound.

Through quorum sensing, Pseudomonas aeruginosa resists noble metal-based nanomaterials toxicity.

Noble metal-based nanomaterials (NMNs), such as platinum nanoparticles (Pt@NPs) and palladium nanoparticles (Pd@NPs), are increasingly being used as antibacterial agents. However, little information is available on bacterial resistance to NMNs. In this study, owing to their oxidase-like and peroxidase-like properties, both Pt@NPs and Pd@NPs induce reactive oxygen species (ROS) and manifest antibacterial activities: 6.25 µg/mL of either Pt@NPs or Pd@NPs killed >50% of Staphylococcus aureus strain ATCC29213. However, Pseudomonas aeruginosa strain PAO1 completely resisted 12.5 µg/mL of Pt@NPs and 6.25 µg/mL of Pd@NPs. Compared to the non-NMN groups, these NMNs promoted 2-3-fold upregulation of the quorum sensing (QS) gene lasR in strain PAO1. In fact, the lasR gene upregulation induced a 1.5-fold reduction in ROS production and increased biofilm formation by 11% (Pt@NPs) and 27% (Pd@NPs) in strain PAO1. The ΔlasR mutants (lasR gene knock out in strain PAO1), became sensitive to NMNs. The survival rates of ΔlasR mutants at 12.5 µg/mL Pt@NPs and Pd@NPs treatments were only 77% and 58%, respectively. This is the first report indicating that bacteria can resist NMNs through QS. Based on these results, evaluation of the ecological risks of using NMNs as antibacterial agents is necessary.

Impact of genetic factors on platinum-induced gastrointestinal toxicity.

Severe gastrointestinal (GI) toxicity is a common side effect after platinum-based chemotherapy. The incidence and severity of GI toxicity vary among patients with the same chemotherapy. Genetic factors involved in platinum transport, metabolism, detoxification, DNA repair, cell cycle control, and apoptosis pathways may account for the interindividual difference in GI toxicity. The influence of gene polymorphisms in the platinum pathway on GI toxicity has been extensively analyzed. Variations in study sample size, ethnicity, design, treatment schedule, dosing, endpoint definition, and assessment of toxicity make it difficult to precisely interpret the results. Hence, we conducted a review to summarize the most recent pharmacogenomics studies of GI toxicity in platinum-based chemotherapy and identify the most promising avenues for further research.

Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer.

Neuroblastoma is the most common extracranial solid tumor in childhood. The different treatments available for neuroblastoma are challenged by high rates of resistance, recurrence, and progression, most notably in advanced cases and highly malignant tumors. Therefore, the development of more targeted therapies, which are biocompatible and without undesired side effects, is highly desirable. The mechanisms of actions of platinum nanoparticles (PtNPs) and retinoic acid (RA) in neuroblastoma have remained unclear. In this study, the anticancer effects of PtNPs and RA on neuroblastoma were assessed. We demonstrated that treatment of SH-SY5Y cells with the combination of PtNPs and RA resulted in improved anticancer effects. The anticancer effects of the two compounds were mediated by cytotoxicity, oxidative stress (OS), mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis-associated networks. Cytotoxicity was confirmed by leakage of lactate dehydrogenase (LDH) and intracellular protease, and oxidative stress increased the level of reactive oxygen species (ROS), 4-hydroxynonenal (HNE), malondialdehyde (MDA), and nitric oxide (NO), and protein carbonyl content (PCC). The combination of PtNPs and RA caused mitochondrial dysfunction by decreasing the mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, number of mitochondria, and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Endoplasmic reticulum-mediated stress and apoptosis were confirmed by upregulation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), activating transcription factor 4 (ATF4), p53, Bax, and caspase-3 and down regulation of B-cell lymphoma 2 (BCl-2). PtNPs and RA induced apoptosis, and oxidative DNA damage was evident by the accumulation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG). Finally, PtNPs and RA increased the differentiation and expression of differentiation markers. Differentiated SH-SY5Y cells pre-treated with PtNPs or RA or the combination of both were more sensitive to the cytotoxic effect of cisplatin than undifferentiated cells. To our knowledge, this is the first study to demonstrate the effect of the combination of PtNPs and RA in neuroblastoma cells. PtNPs may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment. The results of this study provide a rationale for clinical evaluation of the combination of PtNPs and RA for the treatment of children suffering from high-risk neuroblastoma.

Potential use of n-3 PUFAs to prevent oxidative stress-derived ototoxicity caused by platinum-based chemotherapy.

Platinum-based compounds are widely used for the treatment of different malignancies due to their high effectiveness. Unfortunately, platinum-based treatment may lead to ototoxicity, an often-irreversible side effect without a known effective treatment and prevention plan. Platinum-based compound-related ototoxicity results mainly from the production of toxic levels of reactive oxygen species (ROS) rather than DNA-adduct formation, which has led to test strategies based on direct ROS scavengers to ameliorate hearing loss. However, favorable clinical results have been associated with several complications, including potential interactions with chemotherapy efficacy. To understand the contribution of the different cytotoxic mechanisms of platinum analogues on malignant cells and auditory cells, the particular susceptibility and response of both kinds of cells to molecules that potentially interfere with these mechanisms, is fundamental to develop innovative strategies to prevent ototoxicity without affecting antineoplastic effects. The n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) have been tried in different clinical settings, including with cancer patients. Nevertheless, their use to decrease cisplatin-induced ototoxicity has not been explored to date. In this hypothesis paper, we address the mechanisms of platinum compounds-derived ototoxicity, focusing on the differences between the effects of these compounds in neoplastic versus auditory cells. We discuss the basis for a strategic use of n-3 PUFAs to potentially protect auditory cells from platinum-derived injury without affecting neoplastic cells and chemotherapy efficacy.

The role of fish helminth parasites in monitoring metal pollution in aquatic ecosystems: a case study in the world's most productive platinum mining region.

Due to the increasing consumption of platinum (Pt), especially in automobile exhaust catalysts, environmental concentrations of Pt are of emerging concern worldwide. Limited information exists on environmental concentrations, particularly in Pt mining regions, while South Africa is the world's main supplier of Pt. Moreover, other metals are also released as by-products of Pt mining, which might also cause environmental concern. Certain fish parasite taxa have the ability to accumulate metals orders of magnitude higher than their hosts and can be used to reliably detect metals with naturally low abundance. Studies on Pt accumulation in parasite-host systems are limited. Therefore, the aims of the present study were (1) to determine the accumulation of a variety of metals (cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb), platinum (Pt), and zinc (Zn)) in helminth fish parasites compared with their hosts from a reference site and an impoundment impacted by Pt mining activities; (2) to assess whether there is a difference between bioaccumulation of metals in infected and uninfected hosts, as well as between hosts with different infection intensities; and (3) to compare the biomarker responses (acetylcholine esterase activity (AChE), metallothionein content (MT), catalase activity (CAT), reduced glutathione content (GSH), malondialdehyde content (MDA), protein carbonyls induction (PC), superoxide dismutase activity (SOD), and cellular energy allocation (CEA)) between infected and uninfected hosts. The cestode Atractolytocestus huronensis accumulated significantly higher concentrations of Cr, Ni, and Pt than their host Cyprinus carpio, while the nematode Contracaecum sp. accumulated significantly higher concentrations of Pt and Zn than their host Clarias gariepinus. Infected fish showed lower metal concentrations compared to uninfected fish, while the parasites had no significant effects on their hosts' biomarker responses. The parasites demonstrated the bioavailability of metals derived from Pt mining activities and their ability to resist its toxic effects. Thus, these parasites are promising sensitive accumulation indicators for Cr, Ni, Pb, and Pt contaminations from Pt mining activities.

Comparative study of cytotoxicity by platinum nanoparticles and ions in vitro systems based on fish cell lines.

Emission of platinum nanoparticles (Pt NPs) especially from vehicle exhaust catalysts and pharmaceutics cause an increase in concentrations of this metal in aquatic environments. In this study, small (4-9 nm) uncoated and polyvinylpyrrolidone (PVP) coated Pt NPs were synthetized and their dispersion in different exposure media were evaluated. Pt NP uptake in two established fish cell lines were investigated and comparative in vitro cytotoxicity of Pt NPs and ions were assessed. The coated and uncoated Pt NPs dispersions in minimum essential medium (MEM) with fetal bovine serum (FBS) displayed high colloidal stability. Transmission electron microscopy (TEM) and high-resolution scanning electron microscope equipped with an energy-dispersive X-ray spectrometer (STEM/EDX) indicated no detectable cellular uptake of Pt NPs in both cell line monolayers. But with ICP-MS analysis, trace amount of Pt content was determined in all digested monolayer cell samples. The cytotoxicity of both Pt NPs and Pt ions on both fish cell lines after 48 h exposure was investigated through three assays to monitor different endpoints of cytotoxicity. In all studied concentrations (0.325-200 mg/L) no significant cytotoxicity (p > .5) compared to controls were observed in the cells exposed to coated Pt NPs. Uncoated Pt NP and ion exposed cells indicated similar concentration dependent cytotoxicity on both cell lines.

Effect of miR-26b-5p on cis-diamine dichloroplatinum-induced ovarian granulosa cell injury by targeting MAP3K9.

The proliferation and differentiation of granulosa cells are very important for follicular development. The dysfunction of granulosa cells leading to follicular development is an important cause of ovarian endocrine abnormalities. More and more evidence shows that microRNAs are involved in the regulation of ovarian granulosa cell function. It has been found that MiR-26b may be involved in CDDP resistance. Studies have shown that miR-26b can promote apoptosis of ovarian granulosa cells, but there are few studies on its mechanism, and no studies have been found on the damage of miR-26b-5p to rat ovarian granulosa cells induced by CDDP. Identification of ovarian granulosa cells was conducted by immunochemical staining. Cell counting kit 8 (CCK-8) was used to detect cell viability, flow cytometry was used to detect cell apoptosis, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) were used to analyze the expression of miR-26b-5p, MAP3K9, cleaved Caspase-3, Bax, and Bcl-2; dual-luciferase reporter assay results further verify the targeting relation between miR-26b-5p and MAP3K9. CDDP remarkably inhibited ovarian granulosa cell viability and induced ovarian granulosa cell apoptosis; miR-26b-5p inhibitor enhanced viability and inhibited apoptosis of ovarian granulosa cells, which treated with CDDP, but had little effect on normal cells. MAP3K9 partially reversed the effect of miR-26b-5p on ovarian granulosa cells induced by CDDP. miR-26b-5p has a protective effect on CDDP-induced ovarian granulosa cells via targeting MAP3K9.