Metal Toxicity: Effects on Energy Metabolism in Fish

Wang Q., Wu R., Ji J., Zhang J., Niu S., Tang B., Miao B., Liang Z.

Trachinotus ovatus is an economically important mariculture fish, and hypoxia has become a critical threat to this hypoxia-sensitive species. However, the molecular adaptation mechanism of T. ovatus liver to hypoxia remains unclear. In this study, we investigated the effects of acute hypoxic stress (1.5 ± 0.1 mg·L−1 for 6 h) and re-oxygenation (5.8 ± 0.3 mg·L−1 for 12 h) in T. ovatus liver at both the transcriptomic and metabolic levels to elucidate hypoxia adaptation mechanism. Integrated transcriptomics and metabolomics analyses identified 36 genes and seven metabolites as key molecules that were highly related to signal transduction, cell growth and death, carbohydrate metabolism, amino acid metabolism, and lipid metabolism, and all played key roles in hypoxia adaptation. Of these, the hub genes FOS and JUN were pivotal hypoxia adaptation biomarkers for regulating cell growth and death. During hypoxia, up-regulation of GADD45B and CDKN1A genes induced cell cycle arrest. Enhancing intrinsic and extrinsic pathways in combination with glutathione metabolism triggered apoptosis; meanwhile, anti-apoptosis mechanism was activated after hypoxia. Expression of genes related to glycolysis, gluconeogenesis, amino acid metabolism, fat mobilization, and fatty acid biosynthesis were up-regulated after acute hypoxic stress, promoting energy supply. After re-oxygenation for 12 h, continuous apoptosis favored cellular function and tissue repair. Shifting from anaerobic metabolism (glycolysis) during hypoxia to aerobic metabolism (fatty acid β-oxidation and TCA cycle) after re-oxygenation was an important energy metabolism adaptation mechanism. Hypoxia 6 h was a critical period for metabolism alteration and cellular homeostasis, and re-oxygenation intervention should be implemented in a timely way. This study thoroughly examined the molecular response mechanism of T. ovatus under acute hypoxic stress, which contributes to the molecular breeding of hypoxia-tolerant cultivars.

Naz S., Chatha A.M., Téllez-Isaías G., Ullah S., Ullah Q., Khan M.Z., Shah M.K., Abbas G., Kiran A., Mushtaq R., Ahmad B., Kari Z.A.

Metallic trace elements toxicity has been associated with a wide range of morphological abnormalities in fish, both in natural aquatic ecosystems and controlled environments. The bioaccumulation of metallic trace elements can have devastating effects on several aspects of fish health, encompassing physiological, reproductive, behavioural, and developmental functions. Considering the significant risks posed by metallic trace elements-induced toxicity to fish populations, this review aims to investigate the deleterious effects of prevalent metallic trace elements toxicants, such as mercury (Hg), cadmium (Cd), chromium (Cr), lead (Pb), arsenic (As), and copper (Cu), on the neurological, reproductive, embryonic, and tissue systems of fish. Employing diverse search engines and relevant keywords, an extensive review of in vitro and in vivo studies pertaining to metallic trace elements toxicity and its adverse consequences on fish and their organs was conducted. The findings indicate that Cd was the most prevalent metallic trace elements in aquatic environments, exerting the most severe impacts on various fish organs and systems, followed by Cu and Pb. Moreover, it was observed that different metals exhibited varying degrees and types of effects on fish. Given the profound adverse effects of metallic trace elements contamination in water, immediate measures need to be taken to mitigate water pollution stemming from the discharge of waste containing metallic trace elements from agricultural, industrial, and domestic water usage. This study also compares the most common methods for treating metallic trace elements contamination in water.

Sokolov A.V., Moiseenko T.I., Gashkina N.A., Tatsiy Y.G.

The paper discusses modeling the dynamics of nickel concentration in soils, water, and the bottom sediments of lakes caused by atmospheric emissions from the Pechenganickel plant, Kola Peninsula, throughout its whole operation period. The applied technology of balanced identification makes it possible to use a mathematical description of heterogeneous geochemical processes in ecosystems to combine heterogeneous experimental data and build up a computer model with an optimal balance of its complexity and fitting quality of the data. The model is used to analyze the spatial and temporal variability of natural objects in the zone of distribution of atmospheric pollution (nickel) from the Pechenganickel plant. The paper presents and discusses results of this study, including estimates of the retrospective state of the simulated objects (before the start of the intense studies) and a forecast of their dynamics until 2030. According to the model calculations, the intensity of Ni accumulation in the soil and bottom sediments was 2.35 and 4.48 mg/(m2 year) during the maximum deposition periods (1980–2005), whereas the model predicts a decrease in the intensity of Ni accumulation in the bottom sediments (0.23 mg/(m2 year)) and slow Ni leaching from the soil (0.19 mg/(m2 year)) after the shutdown of the plant.

Senoro D.B., Plasus M.M., Gorospe A.F., Nolos R.C., Baaco A.T., Lin C.

Fish is an important source of protein in human meals around the world. However, the fish that we are eating may be contaminated with toxicants such as metals and metalloids (MMs), which may pose health risks to consumers. Information on MMs content in fishes and their potential spatial distribution scenarios would provide knowledge to the community to create strategies and protect human health. Hence, this study assessed and determined the health risk levels of MMs in both brackish and marine water fish (BMF) in Puerto Princesa City (PPC), Palawan Province, Philippines. PPC has an existing abandoned open mine pit near the PPC coastline called the “pit lake”. The concentrations of As, Ba, Cu, Fe, Mn, Hg, and Zn in fishes were analyzed using portable Olympus Vanta X-ray Fluorescence (pXRF), and the spatial distribution of MMs concentrations in BMF was analyzed using a GIS (geographic information system). Fishes were sampled from fishing boat landing sites and nearby seafood markets. The results revealed that the concentration of MMs in marine fish was generally higher than the brackish water fish. It was recorded that the Hg concentration in marine water fish meat was higher than in brackish water fish meat. The Mn concentration in marine water fish exceeded the permissible limits set by international bodies. An elevated concentration of Mn in BMF was detected across the northern part of PPC, and an elevated concentration of Hg in marine fishes was recorded in the southeast area, where the fish landing sites are located. Ba was also detected in BMF across the southern part of PPC. Moreover, an elevated concentration of Cu was detected in MBF in the northeast and in marine fish in the southeastern area of PPC. Further, this paper elaborates the non-carcinogenic and carcinogenic risks of these fishes to the PPC population and tourists with respect to the MMs content in fish meat.

Zhang J., Zhu M., Wang Q., Yang H.

In aquaculture, copper sulphate and trichlorfon are commonly used as disinfectants and insecticide, sometimes in combination. However, improper use can result in biotoxicity and increased ecological risks. The liver plays a crucial role in detoxification, lipid metabolism, nutrient storage, and immune function in fish. Selecting the liver as the main target organ for research helps to gain an in-depth understanding of various aspects of fish physiology, health, and adaptability. In the present study, zebrafish were exposed to Cu (0.5 mg/L) and Tri (0.5 mg/L) alone and in combination for 21 days. The results demonstrate that both Cu and Tri caused hepatocyte structure damage in zebrafish after 21 days of exposure, with the combination showing an even greater toxicity. Additionally, the antioxidant and immune enzyme activities in zebrafish liver were significantly induced on both day 7 and day 21. A transcriptome analysis revealed that Cu and Tri, alone and in combination, impacted various physiological activities differently, including metabolism, growth, and immunity. Overall, Cu and Tri, either individually or in combination, can induce tissue damage by generating oxidative stress in the body, and the longer the exposure duration, the stronger the toxic effects. Moreover, the combined exposure to Cu and Tri exhibits enhanced toxicity. This study provides a theoretical foundation for the combined use of heavy metal disinfectants and other drugs.

Surenbaatar U., Lee S., Kwon J., Lim H., Kim J., Kim Y., Hong Y.

Soil contamination is associated with a high potential for health issues. This study aimed to investigate the bioaccumulation of heavy metals and its associated health impact among residents near a mining area. We performed environmental monitoring by analyzing lead (Pb), cadmium (Cd), and arsenic (As) levels in soil and rice samples, as well as biomonitoring by analyzing blood and urine samples from 58 residents living near the mine. Additionally, concentration trends were investigated among 26 participants in a 2013 study. The Cd and As levels in the soil samples and Cd levels in the rice samples exceeded the criteria for concern. The geometric mean blood Cd level (2.12 μg/L) was two times higher than that in the general population aged > 40 years. The blood Cd level showed decreasing trends from the previous measurements of 4.56–2.25 μg/L, but was still higher than that in the general population. The blood and urine Cd levels were higher in those with a low estimated glomerular filtration rate (eGFR) than in those with normal eGFR. In conclusion, heavy metals from mining areas can accumulate in soil and rice, adversely impacting human health. Continuous environmental monitoring and biomonitoring are required to ensure the safety of residents.

Jamil Emon F., Rohani M.F., Sumaiya N., Tuj Jannat M.F., Akter Y., Shahjahan M., Abdul Kari Z., Tahiluddin A.B., Goh K.W.

Heavy metals, the most potent contaminants of the environment, are discharged into the aquatic ecosystems through the effluents of several industries, resulting in serious aquatic pollution. This type of severe heavy metal contamination in aquaculture systems has attracted great attention throughout the world. These toxic heavy metals are transmitted into the food chain through their bioaccumulation in different tissues of aquatic species and have aroused serious public health concerns. Heavy metal toxicity negatively affects the growth, reproduction, and physiology of fish, which is threatening the sustainable development of the aquaculture sector. Recently, several techniques, such as adsorption, physio-biochemical, molecular, and phytoremediation mechanisms have been successfully applied to reduce the toxicants in the environment. Microorganisms, especially several bacterial species, play a key role in this bioremediation process. In this context, the present review summarizes the bioaccumulation of different heavy metals into fishes, their toxic effects, and possible bioremediation techniques to protect the fishes from heavy metal contamination. Additionally, this paper discusses existing strategies to bioremediate heavy metals from aquatic ecosystems and the scope of genetic and molecular approaches for the effective bioremediation of heavy metals.

Raposo de Magalhães C., Farinha A.P., Blackburn G., Whitfield P.D., Carrilho R., Schrama D., Cerqueira M., Rodrigues P.M.

The study of the molecular mechanisms of stress appraisal on farmed fish is paramount to ensuring a sustainable aquaculture. Stress exposure can either culminate in the organism’s adaptation or aggravate into a metabolic shutdown, characterized by irreversible cellular damage and deleterious effects on fish performance, welfare, and survival. Multiomics can improve our understanding of the complex stressed phenotype in fish and the molecular mediators that regulate the underlying processes of the molecular stress response. We profiled the stress proteome and metabolome of Sparus aurata responding to different challenges common to aquaculture production, characterizing the disturbed pathways in the fish liver, i.e., the central organ in mounting the stress response. Label-free shotgun proteomics and untargeted metabolomics analyses identified 1738 proteins and 120 metabolites, separately. Mass spectrometry data have been made fully accessible via ProteomeXchange, with the identifier PXD036392, and via MetaboLights, with the identifier MTBLS5940. Integrative multivariate statistical analysis, performed with data integration analysis for biomarker discovery using latent components (DIABLO), depicted the 10 most-relevant features. Functional analysis of these selected features revealed an intricate network of regulatory components, modulating different signaling pathways related to cellular stress, e.g., the mTORC1 pathway, the unfolded protein response, endocytosis, and autophagy to different extents according to the stress nature. These results shed light on the dynamics and extent of this species’ metabolic reprogramming under chronic stress, supporting future studies on stress markers’ discovery and fish welfare research.

Arnst N., Redolfi N., Lia A., Bedetta M., Greotti E., Pizzo P.

Alzheimer’s disease (AD) is a hereditary and sporadic neurodegenerative illness defined by the gradual and cumulative loss of neurons in specific brain areas. The processes that cause AD are still under investigation and there are no available therapies to halt it. Current progress puts at the forefront the “calcium (Ca2+) hypothesis” as a key AD pathogenic pathway, impacting neuronal, astrocyte and microglial function. In this review, we focused on mitochondrial Ca2+ alterations in AD, their causes and bioenergetic consequences in neuronal and glial cells, summarizing the possible mechanisms linking detrimental mitochondrial Ca2+ signals to neuronal death in different experimental AD models.

Ngo H.T., Nguyen T.D., Nguyen T.T., Le T.T., Nguyen D.Q.

Toxic metal pollution influences the lives of diverse aquatic organisms and humans who consume contaminated aquatic products. However, its potential impacts on aquatic organism health and, thus, ecological health, have been neglected in many regions. This research was carried out to contribute to filling that knowledge gap. Three freshwater fish species in the Nhue–Day River basin, Vietnam, have been chosen to study the bioaccumulation of metals (Zn, Cu, Pb, and Cd) in the tissues (livers, kidneys, gills) and their effects on fish physiological health (changes in the oxidative-GST activity, and physiological biomarkers-energy reserves, respectively) from 2013 to 2017. The extensive results revealed significant spatial and temporal variations in metal concentrations in tissues of common carp (Cyprinus carpio), silver carp (Hypothalmic molitrix), and tilapia (Oreochromis niloticus), and well correlated to their concentration in the water (p < 0.05). Fish bioaccumulated metals in the following order: Zn > Cu > Pb > Cd, with more in the kidneys and livers (spring and summer) than in other tissues. Metal accumulation in O. niloticus and C. carpio was higher than in H. molitrix. Biomarker responses (except for glycogen variation) were also higher during warm seasons. Changes in metal levels in water and fish tissues caused variations in biomarkers in the respective fish tissues, particularly in the livers, as demonstrated by significant correlations of metal concentrations in water and fish tissues to biochemical and physiological responses (p < 0.05). The findings suggest that metal pollution in the river basin adversely impacts the physiological health of both wild and cultured fish. Seasonal shifts in the levels of metal accumulation and biomarkers could be connected to species-specific differences in physiology and the levels of metals in environments. This biomarker set is simple but effective in assessing the impact of metal pollution on fish health and, hence, the aquatic ecosystem. This is one of the first biomonitoring studies to assist in designing better water management strategies for the Nhue–Day River basin.

Gashkina N.A., Moiseenko T.I., Shuman L.A., Koroleva I.M.

Bioaccumulation of the main pollutants in the organs of whitefish, as well as their haematological parameters, were examined dynamically over a 40-year period in historically contaminated Lake Imandra. A quantitative histological analysis was performed to assess the physiological state of whitefish and histopathologies of organs, as well as their physiological and biochemical functions in the current period of toxic load decline. Biological reactions of whitefish from the historically contaminated area have been greatly modified in contrast to those of whitefish from the never contaminated area of the lake, and this shift persisted even after approximately 20 years of toxic load decline. First, high antioxidant status supports the body's systems, smoothing over the negative consequences of metal toxicity, phagocytosis and inflammatory reactions. Moreover, the defence mechanism of whitefish from the historically contaminated area actively uses the oxidative systems of nonspecific immunity. Second, the adaptive strategy is aimed at improving gas exchange without compensatory proliferation of gill structure, which increases their functional surface and reduces the distance to the bloodstream, as well as increasing haemoglobin in maturing erythrocytes. Third, the higher efficiency of endo- and phagocytosis was confirmed by detecting increased monocytes and macrophages in the peripheral blood and decreased melano-macrophage centres in the fish kidney. Elevated accumulation of Fe, Cu, and Se may serve a sign of liver pathology, while elevated accumulation of Zn and Co already indicates kidney pathology, which is confirmed by histopathological alterations. • Biological reactions of whitefish from historically contaminated area have been modified: • high antioxidant status supports the body's systems. • oxidative systems of nonspecific immunity dominate in protective functions. • adaptive strategy is aimed at improving gas exchange and increasing haemoglobin in erythrocytes. • high efficiency of endo- and phagocytosis is typical for fish.

Saiz N., Herrera-Castillo L., Isorna E., Delgado M.J., Conde-Sieira M., Soengas J.L., de Pedro N.

REV-ERBα (nr1d1, nuclear receptor subfamily 1 group D member 1) is a transcriptional repressor that in mammals regulates nutrient metabolism, and has effects on energy homeostasis, although its role in teleosts is poorly understood. To determine REV-ERBα’s involvement in fish energy balance and metabolism, we studied the effects of acute and 7-day administration of its agonist SR9009 on food intake, weight and length gain, locomotor activity, feeding regulators, plasma and hepatic metabolites, and liver enzymatic activity. SR9009 inhibited feeding, lowering body weight and length gain. In addition, the abundance of ghrelin mRNA decreased in the intestine, and abundance of leptin-aI mRNA increased in the liver. Hypocretin, neuropeptide y (npy), and proopiomelanocortin (pomc) mRNA abundance was not modified after acute or subchronic SR9009 administration, while hypothalamic cocaine- and amphetamine-regulated transcript (cartpt-I) was induced in the subchronic treatment, being a possible mediator of the anorectic effects. Moreover, SR9009 decreased plasma glucose, coinciding with increased glycolysis and a decreased gluconeogenesis in the liver. Decreased triglyceride levels and activity of lipogenic enzymes suggest a lipogenesis reduction by SR9009. Energy expenditure by locomotor activity was not significantly affected by SR9009. Overall, this study shows for the first time in fish the effects of REV-ERBα activation via SR9009, promoting a negative energy balance by reducing energetic inputs and regulating lipid and glucose metabolism.

Lall S.P., Kaushik S.J.

Aquatic animals have unique physiological mechanisms to absorb and retain minerals from their diets and water. Research and development in the area of mineral nutrition of farmed fish and crustaceans have been relatively slow and major gaps exist in the knowledge of trace element requirements, physiological functions and bioavailability from feed ingredients. Quantitative dietary requirements have been reported for three macroelements (calcium, phosphorus and magnesium) and six trace minerals (zinc, iron, copper, manganese, iodine and selenium) for selected fish species. Mineral deficiency signs in fish include reduced bone mineralization, anorexia, lens cataracts (zinc), skeletal deformities (phosphorus, magnesium, zinc), fin erosion (copper, zinc), nephrocalcinosis (magnesium deficiency, selenium toxicity), thyroid hyperplasia (iodine), muscular dystrophy (selenium) and hypochromic microcytic anaemia (iron). An excessive intake of minerals from either diet or gill uptake causes toxicity and therefore a fine balance between mineral deficiency and toxicity is vital for aquatic organisms to maintain their homeostasis either through increased absorption or excretion. Release of minerals from uneaten or undigested feed and from urinary excretion can cause eutrophication of natural waters, which requires additional consideration in feed formulation. The current knowledge in mineral nutrition of fish is briefly reviewed.

Paschoalini A.L., Bazzoli N.

• Detailed studies were performed principally in Brazil, Argentina, and Colombia. • The most studied organs were the gills, liver and muscle. • Molecular to behavioral effects have been detected in Neotropical species. • Effects in reproductive and nervous systems have rarely been assessed. • Studies in wild populations were more frequent than experimental studies. The expansion of urban centers, the increase in the use of chemicals in agriculture, and the significant expansion of industry has dumped increasing amounts of heavy metals into aquatic ecosystems, directly and indirectly affecting the entire food web in freshwater environments. In freshwater fish, many studies conducted worldwide have shown that these pollutants can cause alterations from the molecular level to behavioral, in all stages of life, including in future generations. Despite the great diversity of freshwater fish in the Neotropical region, few studies addressing the influence of metals on native species have been carried out. The last decade of studies showed that the effects of metals in neotropical species can be from the molecular to the behavioral level. Metals like Arsenic, Cadmium, Copper, Lead, Mercury, Chromium and Zinc have often been detected in environmental studies and evaluated in experimental approaches. Metabolically active organs showed higher levels of accumulation. In addition, some environmental studies have shown that ecologic and trophic conditions can be determinant in the level of exposure to metals. Oxidative stress, genotoxicity and several histopathological alterations were the most recurrent effects detected in target organs.

Wang X., An P., Gu Z., Luo Y., Luo J.

Mitochondria are vital to life and provide biological energy for other organelles and cell physiological processes. On the mitochondrial double layer membrane, there are a variety of channels and transporters to transport different metal ions, such as Ca2+, K+, Na+, Mg2+, Zn2+ and Fe2+/Fe3+. Emerging evidence in recent years has shown that the metal ion transport is essential for mitochondrial function and cellular metabolism, including oxidative phosphorylation (OXPHOS), ATP production, mitochondrial integrity, mitochondrial volume, enzyme activity, signal transduction, proliferation and apoptosis. The homeostasis of mitochondrial metal ions plays an important role in maintaining mitochondria and cell functions and regulating multiple diseases. In particular, channels and transporters for transporting mitochondrial metal ions are very critical, which can be used as potential targets to treat neurodegeneration, cardiovascular diseases, cancer, diabetes and other metabolic diseases. This review summarizes the current research on several types of mitochondrial metal ion channels/transporters and their functions in cell metabolism and diseases, providing strong evidence and therapeutic strategies for further insights into related diseases.

Selinger S.J., Montgomery D., Wiseman S., Hecker M., Weber L., Brinkmann M., Janz D.

Wang Z., Ye H., Liu P., Lin S., Wang Y., Zhou Q., Jiang H., Shao J.

Qualhato G., Cirqueira F., Rocha T.L.

Facial masks are a source of plastic microfibres (PMFs) in the aquatic environment, an emerging risk factor for aquatic organisms. However, little is known concerning its impact during the early developmental stages of fish. Thus, the current study aimed to evaluate the potential interaction and developmental toxicity of PMFs derived from leachate of surgical masks (SC-Msk) and N-95 facial masks (N95-Msk) using a multi-biomarker approach in developing zebrafish (Danio rerio). PMFs from both facial masks were obtained and characterized by multiple techniques. Zebrafish embryos were exposed to environmentally relevant concentrations of PMFs from both facial masks (1000, 10,000, and 100,000 particle L