Eco-endocrinological dynamics: Unraveling dexamethasone's influence on the interrenal axis in juvenile carp Cyprinus carpio.

This study delves into the eco-endocrinological dynamics concerning the impact of dexamethasone (DXE) on the interrenal axis in juvenile carp, Cyprinus carpio. Through a comprehensive analysis, we investigated the effects of DXE exposure on oxidative stress, biochemical biomarkers, gene expression, and bioaccumulation within the interrenal axis. Results revealed a concentration-dependent escalation of cellular oxidation biomarkers, including 1) hydroperoxides content (HPC), 2) lipid peroxidation level (LPX), and 3) protein carbonyl content (PCC), indicative of heightened oxidative stress. Concurrently, the activity of critical antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT), significantly increased, underscoring the organism's response to oxidative insult. Notable alterations were observed in biochemical biomarkers, particularly Gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) activity, with GGT displaying a significant decrease with increasing DXE concentrations. Gene expression analysis revealed a significant upregulation of stress and inflammation response genes, as well as those associated with sensitivity to superoxide ion presence and calcium signaling, in response to DXE exposure. Furthermore, DXE demonstrated a concentration-dependent presence in interrenal tissue, with consistent bioconcentration factors observed across all concentrations tested. These findings shed light on the physiological and molecular responses of juvenile carp to DXE exposure, emphasizing the potential ecological implications of DXE contamination in aquatic environments. Understanding these dynamics is crucial for assessing the environmental impact of glucocorticoid pollutants and developing effective management strategies to mitigate their adverse effects on aquatic ecosystems.

Assessing the impact of COVID-19 era drug combinations on hepatic functionality: A thorough investigation in adult Danio rerio.

Current and thorough information on the ecotoxicological consequences of pharmaceuticals is accessible globally. However, there remains a substantial gap in knowledge concerning the potentially toxic effects of COVID-19 used drugs, individually and combined, on aquatic organisms. Given the factors above, our investigation assumes pivotal importance in elucidating whether or not paracetamol, dexamethasone, metformin, and their tertiary mixtures might prompt histological impairment, oxidative stress, and apoptosis in the liver of zebrafish. The findings indicated that all treatments, except paracetamol, augmented the antioxidant activity of superoxide dismutase (SOD) and catalase (CAD), along with elevating the levels of oxidative biomarkers such as lipid peroxidation (LPX), hydroperoxides (HPC), and protein carbonyl content (PCC). Paracetamol prompted a reduction in the activities SOD and CAT and exhibited the most pronounced toxic response when compared to the other treatments. The gene expression patterns paralleled those of oxidative stress, with all treatments demonstrating overexpression of bax, bcl2, and p53. The above suggested a probable apoptotic response in the liver of the fish. Nevertheless, our histological examinations revealed that none of the treatments induced an apoptotic or inflammatory response in the hepatocytes. Instead, the observed tissue alterations encompassed leukocyte infiltration, sinusoidal dilatation, pyknosis, fatty degeneration, diffuse congestion, and vacuolization. In summary, the hepatic toxicity elicited by COVID-19 drugs in zebrafish was less pronounced than anticipated. This attenuation could be attributed to metformin's antioxidant and hormetic effects.

Acute exposure to fluoxetine leads to oxidative stress and hematological disorder in Danio rerio adults.

Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), is consistently introduced into the environment due to its ongoing consumption and inadequate removal by wastewater treatment plants. As a result, the scientific community has displayed a keen interest in investigating the potential toxicological effects associated with this medication. Nevertheless, there is a scarcity of available data regarding the impact of FLX on blood parameters. With this in mind, this study aimed to evaluate the potential toxicological consequences of FLX at environmentally significant concentrations (5, 16, and 40 ng/L) following a 96-hour acute exposure blood parameters in Danio rerio fish. Moreover, the investigation encompassed an assessment of oxidative stress parameters to determine whether the drug could induce disruptions in the REDOX status of the fish. The findings unveiled that FLX prompted the induction of oxidative stress in various organs of the fish, encompassing the liver, gut, brain, and gills. Notably, the gills and brain exhibited heightened susceptibility to the drug's effects compared to other organs. Furthermore, following acute exposure to FLX, there was an upregulation of antioxidant-related genes (sod, cat, gpx, nrf1, and nrf2), thereby providing additional evidence supporting the induction of oxidative stress in the organs of the fish. Lastly, FLX significantly impacted the customary values of various blood parameters, including glucose, blood urea nitrogen, alanine aminotransferase, alkaline phosphatase, red blood cell count, hemoglobin, and hematocrit. Thus, it can be inferred that FLX harmed the overall health status of the fish, resulting in the development of liver disease, anemia, and other associated illnesses.

Short-term exposure to dexamethasone at environmentally relevant concentrations impairs embryonic development in Cyprinus carpio: Bioconcentration and alteration of oxidative stress-related gene expression patterns.

In recent years and as a result of the Covid-19 pandemic, the consumption of dexamethasone (DXE) has increased. This favors that this corticosteroid is highly released in aquatic environments, generating deleterious effects in aquatic organisms. The information on the toxic effects of DXE in the environment is still limited. Thus, the objective of this work was to determine whether DXE at short-term exposure can cause alterations to embryonic development and alteration of oxidative stress-related gene expression patterns in Cyprinus carpio. For this purpose, common carp embryos (2 hpf) were exposed to realistic concentrations of DXE until 96 hpf. Alterations to embryonic development were evaluated at 12, 24, 48, 72 and 96 hpf. In addition, oxidative stress in carp embryos at 72 and 96 hpf was evaluated by cellular oxidation biomarkers (lipoperoxidation level, hydroperoxide and carbonyl protein content) and antioxidant enzymes activities (superoxide dismutase and catalase). Oxidative stress-related gene expression (sod, cat and gpx1) was also evaluated. Our results showed that DXE concentrations above 35 ng/L are capable of producing alterations to embryonic development in 50 % of the embryo population. Furthermore, DXE was able to induce alterations such as scoliosis, hypopigmentation, craniofacial malformations, pericardial edema and growth retardation, leading to the death of half of the population at 50 ng/L of DXE. Concerning oxidative stress, the results demonstrated that DXE induce oxidative damage on the embryos of C. carpio. In conclusion, DXE is capable of altering embryonic development and generating oxidative stress in common carp C. carpio.

Acute exposure to realistic concentrations of Bisphenol-A trigger health damage in fish: Blood parameters, gene expression, oxidative stress.

Despite much information regarding BPA toxicity in fish and other aquatic organisms, data is still misleading as most studies have utilized concentrations several orders of magnitude higher than those typically found in the environment. As an illustration, eight of the ten studies investigating the impact of BPA on the biochemical and hematological parameters of fish have employed concentrations on the order of mg/L. Therefore, the results may not accurately represent the effects observed in the natural environment. Considering the information above, our study aimed to 1) determine whether or not realistic concentrations of BPA might alter the biochemical and blood parameters of Danio rerio and trigger an inflammatory response in the fish liver, brain, gills, and gut and 2) determine which organ could be more affected after exposure to this chemical. Findings pinpoint that realistic concentrations of BPA prompted a substantial increase in antioxidant and oxidant biomarkers in fish, triggering an oxidative stress response in all organs. Likewise, the expression of different genes related to inflammation and apoptosis response was significantly augmented in all organs. Our Pearson correlation shows gene expression was closely associated with the oxidative stress response. Regarding blood parameters, acute exposure to BPA generated biochemical and hematological parameters increased concentration-dependent. Thus, it can be concluded that BPA, at environmentally relevant concentrations, threatens aquatic species, as it prompts polychromasia and liver dysfunction in fish after acute exposure.

Oxidative stress as regulator of neuronal impairment after exposure to hospital effluents in Danio rerio.

The variety of activities carried out within hospitals results in their final discharges being considered hotspots for the emission of emerging pollutants. Hospital effluents contain different substances capable of altering the health of ecosystems and biota, furthermore, little research has been done to elucidate the adverse effects of these anthropogenic matrices. Taking this into account, herein we aimed to establish whether exposure to different proportions (2 %, 2.5 %, 3 %, and 3.5 %) of hospital effluent treated by hospital wastewater treatment plant (HWWTP) can induce oxidative stress, behavioral alterations, neurotoxicity, and disruption of gene expression in Danio rerio brain. Our results demonstrate that the hospital effluent under-study induces an anxiety-like state and alters swimming behavior, as fish exhibited increased freezing episodes, erratic movements and traveled less distance than the control group. In addition, after exposure we observed a meaningful rise in biomarkers related to oxidative damage, such as protein carbonyl content (PCC), lipoperoxidation level (LPX), hydroperoxide content (HPC), as well as an increase in enzyme antioxidant activities of catalase (CAT), and superoxide dismutase (SOD) upon short-term exposure. Moreover, we discovered an inhibition of acetylcholinesterase (AChE) activity in a hospital effluent proportion-dependent manner. Regarding gene expression, a significant disruption of genes related to antioxidant response (cat, sod, nrf2), apoptosis (casp6, bax, casp9), and detoxification (cyp1a1) was observed. In conclusion, our outcomes suggest that hospital effluents enhance the emergence of oxidative molecules, and promote a highly oxidative environment at the neuronal level that favors the inhibition of AChE activity, which consequently explains the anxiety-like behavior observed in D. rerio adults. Lastly, our research sheds light on possible toxicodynamic mechanism by which these anthropogenic matrices may trigger damage in D. rerio brain.

Integrative approach to elucidate the embryological effects of caffeine in Cyprinus carpio: Bioconcentration and alteration of oxidative stress-related gene expression patterns.

Caffeine (CAF) is an alkaloid, which acts as a central nervous system (CNS) stimulant drug. In recent years, CAF has been recurrently detected in water bodies, generating deleterious effects in aquatic organisms. The information on the toxic effects of CAF in the environment is still limited. Thus, the objective of this work was to determine whether CAF at environmentally relevant concentrations (CAF concentrations were selected based on studies on the worldwide occurrence of this compound and on the toxicity of CAF in aquatic species) is capable of inducing alterations to embryonic development and alteration of oxidative stress-related gene expression patterns in Cyprinus carpio. For this purpose, common carp embryos (2 hpf) were exposed to realistic concentrations of CAF until 96 hpf. Alterations to embryonic development and teratogenic effects were evaluated at 12, 24, 48, 72 and 96 hpf. In addition, oxidative stress in carp embryos at 72 and 96 hpf was evaluated by cellular oxidation biomarkers (lipoperoxidation level, hydroperoxide content and carbonyl protein content) and antioxidant enzymes activities (superoxide dismutase and catalase). Oxidative stress-related gene expression (sod, cat and gpx1) was also evaluated. Our results showed that CAF concentrations above 500 ng/L are capable of producing teratogenic effects. Furthermore, CAF was able to induce alterations such cardiac malformations, somite alterations, pericardial edema and chorda malformations. Concerning oxidative stress, the results demonstrated that CAF induce oxidative damage on the embryos of C. carpio. Our outcomes also showed up-regulations in genes related to antioxidant activity sod, cat and gpx by CAF exposure. In conclusion CAF at environmentally relevant concentrations is able to alter the embryonic development of common carp by the oxidative stress pathway. Based on the above evidence, it can be inferred that acute exposure to CAF can lead to a toxic response that significantly harms fish's health, adversely affecting their essential organs' functioning.

Realistic concentrations of Bisphenol-A trigger a neurotoxic response in the brain of zebrafish: Oxidative stress, behavioral impairment, acetylcholinesterase inhibition, and gene expression disruption.

Bisphenol A (BPA) is a micro-pollutant found in various environmental matrices at concentrations as low as ng/L. Recent studies have shown that this compound can cause oxidative damage and neurotoxic effects in aquatic organisms. However, there is a lack of research investigating the effects of BPA at environmentally relevant concentrations. Therefore, this study aimed to assess the neurotoxic effects of acute BPA exposure (96 h) at environmentally relevant concentrations (220, 1180, and 1500 ng/L) in adult zebrafish (Danio rerio). The Novel Tank trial was used to evaluate fish swimming behavior, and our results indicate that exposure to 1500 ng/L of BPA reduced the total distance traveled and increased freezing time. Furthermore, the evaluation of biomarkers in the zebrafish brain revealed that BPA exposure led to the production of reactive oxygen species and increased acetylcholinesterase activity. Gene expression analysis also indicated the overexpression of mbp, α1-tubulin, and manf in the zebrafish brain. Based on our findings, we concluded that environmentally relevant concentrations of BPA can cause anxiety-like behavior and neurotoxic effects in adult zebrafish.

The evaluation of liver dysfunction and oxidative stress due to urban environmental pollution in Mexican population related to Madin Dam, State of Mexico: a pilot study.

One of the most important causes of disease and premature death in the world is environmental pollution. The presence of pollutants in both water and air contributes to the deterioration of the health of human populations. The Mexico City Metropolitan Area is one of the most populous and affected by air pollution worldwide; in addition, in recent years there has been a growing demand for water, so urban reservoirs such as the Madin dam are vital to meet the demand. However, this reservoir is highly polluted due to the urban settlements around it. Therefore, the aim of the present study was to evaluate oxidative stress in clinically healthy subjects by means of the degree of lipoperoxidation, as well as the modification of serum enzyme levels, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase associated with air and drinking water pollutants from three zones of the Mexico City Metropolitan Area, two of them related to Madin Dam. This descriptive cross-sectional study was conducted between March 2019 and September 2021 in 142 healthy participants (age range 18-65 years). Healthy subjects were confirmed by their medical history. The results showed that chronic exposure to air (SO2) and water pollutants (Al and Fe) was significantly associated with elevated levels of lipoperoxidation. There was evidence that contamination from the Madín dam can generate oxidative stress and affect the health status of people who receive water from this reservoir or who consume fish that inhabit it.

Polystyrene microplastics mitigate the embryotoxic damage of metformin and guanylurea in Danio rerio.

Microplastics (MPs) alone may endanger the health and fitness of aquatic species through different mechanisms. However, the harmful effects of these when mixed with other emerging contaminants require additional research. Herein, we aimed to determine whether a mixture of MPs with metformin (MET) or guanylurea (GUA) might induce embryotoxicity and oxidative stress in Danio rerio. Upon exposure to mixtures, our results showed MPs reduced the mortality rate of MET and GUA in embryos. Moreover, the severity and the rate of malformations were also decreased in all mixtures with MPs. Concerning oxidative stress, our findings indicated MET, GUA, MPs, and the mixtures increased the levels of lipoperoxidation, hydroperoxide content, and protein carbonyl content in D. rerio larvae. However, the oxidative damage induced in all mixtures was lower than that produced by both drugs alone. Thus, it is likely that the accumulation of MPs avoided the entrance of MET and GUA into the embryos. Once the embryo hatched, MPs did only remain accumulated in the yolk sac of larvae and did not translocate to other organs. Our risk assessment analysis confirmed that MPs shrunk the damage produced by MET and GUA. In a nutshell, MPs mitigate the embryotoxic damage of metformin and guanylurea in D. rerio by blocking their entrance.

Chronic exposure to realistic concentrations of metformin prompts a neurotoxic response in Danio rerio adults.

Metformin (MET) is among the most consumed drugs around the world, and thus, it is considered the uppermost drug in mass discharged into water settings. Nonetheless, data about the deleterious consequences of MET on water organisms are still scarce and require further investigation. Herein, we aimed to establish whether or not chronic exposure to MET (1, 20, and 40 µg/L) may alter the swimming behavior and induce neurotoxicity in Danio rerio adults. After 4 months of exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. Our findings demonstrate that chronic exposure to MET may impair fish swimming behavior, making them more vulnerable to predators.

Integrated adsorption and biological removal of the emerging contaminants ibuprofen, naproxen, atrazine, diazinon, and carbaryl in a horizontal tubular bioreactor.

Groundwater and surface water bodies may have contaminants from urban, industrial, or agricultural wastewater, including emerging contaminants (ECs) or micropollutants (MPs). Frequently, they are not efficiently removed by microbial action due to their minimal concentration in water and the low microbiota affinity for complex compounds. This work developed a process allowing the adsorption of contaminants and their simultaneous biodegradation using horizontal tubular fixed-bed biofilm reactors (HTR). Each HTR has two zones: an equalizer-aerator of the incoming liquid flow and a fixed bed zone. This zone was packed with a mixed support material consisting of granular bio-activated carbon (Bio-GAC) and porous material that increases the bed permeability, thus decreasing the pressure drop. Five microbial communities were acclimated and immobilized in granular activated carbon (GAC) to obtain different specialized Bio-GAC particles able to remove the micropollutants ibuprofen, naproxen, atrazine, carbaryl, and diazinon. The Bio-GAC particles were transferred to HTRs continuously run in microaerophilia at several MPs loading rates. Under these conditions, the removal efficiencies of MPs, except atrazine and carbaryl, were around 100.

Multi-biomarker approach and IBR index to evaluate the effects of bisphenol A on embryonic stages of zebrafish (Danio rerio).

This study assessed the effects of Bisphenol A in embryonic stages of zebrafish, applying an IBR multi-biomarker approach that included alterations in growth and oxidative status and relates it with the expression of Nrf1, Nrf2, Wnt3a, Wnt8a, COX-2, Qdpra, and DKK1 genes. For this purpose, we exposed zebrafish embryos to eight environmentally relevant concentrations of BPA (220, 380, 540, 700, 860, 1180, 1340, and 1500 ng L-1) until 96 h post-fertilization. Our results show that BPA induces several malformations in embryos (developmental delay, hypopigmentation, tail malformations, and on), leading to their death. The LC50, EC50 of malformations, and teratogenic index (TI) were 1234.60 ng L-1, 987.77 ng L-1, and 1.25, respectively; thus, this emerging contaminant is teratogenic. Regarding oxidative stress and gene expression, we demonstrated BPA altered oxidative status and the gene expression in embryos of Danio rerio.

Multi-biomarker approach to evaluate the neurotoxic effects of environmentally relevant concentrations of phenytoin on adult zebrafish Danio rerio.

Several studies have reported the presence of phenytoin (PHE) in wastewater treatment plant effluents, hospital effluents, surface water, and even drinking water. However, published studies on the toxic effects of PHE at environmentally relevant concentrations in aquatic organisms are scarce. The present study aimed to determine the effect of three environmentally relevant concentrations of PHE (25, 282, and 1500 ng L-1) on behavioral parameters using the novel tank test. Moreover, we also aimed to determine whether or not these concentrations of PHE may impair acetylcholinesterase (AChE) activity and oxidative status in the brain of Danio rerio adults. Behavioral responses suggested an anxiolytic effect in PHE-exposed organisms, mainly observed in organisms exposed to 1500 ng L-1, with a significant decrease in fish mobility and a significant increase in activity at the top of the tank. Besides the behavioral impairment, PHE-exposed fish also showed a significant increase in the levels of lipid peroxidation, hydroperoxides, and protein carbonyl content compared to the control group. Moreover, a significant increase in brain AChE levels was observed in fish exposed to 282 and 1500 ng L-1. The results obtained in the present study show that PHE triggers a harmful response in the brain of fish, which in turn generates fish have an anxiety-like behavior.

Acute exposure to environmentally relevant concentrations of sucralose disrupts embryonic development and leads to an oxidative stress response in Danio rerio.

Sucralose (SUC) is the most consumed artificial sweetener worldwide, not metabolized by the human body, and barely eliminated from water in wastewater treatment plants. Although different studies have reported high concentrations of this sweetener in aquatic environments, limited to no information is known about the toxic effects this drug may produce over water organisms. Moreover, most of the current studies have used non-environmentally relevant concentrations of SUC for these effects. Herein, we aimed to evaluate the harmful effects that environmentally relevant concentrations of SUC may induce in the early life stages of Danio rerio. According to our results, SUC altered the embryonic development of D. rerio, producing several malformations that led to their death. The major malformations were scoliosis, pericardial edema, yolk deformation, and tail malformation. However, embryos also got craniofacial malformations, eye absence, fin absence, dwarfism, delay of the hatching process, and hypopigmentation. SUC also generated an oxidative stress response in the embryos characterized by an increase in the levels of lipid peroxidation, hydroperoxides, and carbonyl proteins. To overcome this oxidative stress response, we observed a significant increase in the levels of antioxidant enzymes superoxide dismutase and catalase. Moreover, a significant boost in the expression of antioxidant defense-related genes, Nuclear respiratory factor 1a (Nrf1a) and Nuclear respiratory factor 2a (Nrf2a), was also observed at all concentrations. Concerning apoptosis-related genes, we observed the expression of Caspase 3 (CASP3) and Caspase 9 (CASP9) was increased in a concentration-dependent manner. Overall, we conclude environmentally relevant concentrations of SUC are harmful to the early life stages of fish as they produce malformations, oxidative stress, and increased gene expression of apoptosis-related genes on embryos.

Fluoxetine-induced neurotoxicity at environmentally relevant concentrations in adult zebrafish Danio rerio.

Fluoxetine (FLX) exerts its therapeutic effect by inhibiting the presynaptic reuptake of the neurotransmitter serotonin. Nonetheless, at high concentrations of this drug, adverse effects occur in the brain of exposed organisms. Bearing this into account, the objective of this study was to evaluate the neurotoxic effects of the fluoxetine through the evaluation of behavior (Novel tank test), determination of oxidative stress, and determination of acetylcholinesterase (AChE) activity in adult zebrafish Danio rerio. For this purpose, Danio rerio adults were exposed to three environmentally relevant concentrations (5, 10, 16 ng L-1) of FLX for 96 h. Our results demonstrate fish presented a significant disruption in their behavior, as they remained long-lasting time frozen at the top of the tank. Since we observed a significant reduction of AChE activity in the brain of fish, we believe the above described anxiety-like state is the result of this enzyme impairment. Moreover, as FLX-exposed fish showed a significant increase in the levels of oxidative damage biomarkers, we suggest this AChE disruption is associated with the oxidative stress response fish exhibited. Based on our findings, we believe the environmentally relevant concentration of FLX alters the redox status of the brain, impairing this way the behavior of fish and making them more vulnerable to predation.

Brain damage induced by contaminants released in a hospital from Mexico: Evaluation of swimming behavior, oxidative stress, and acetylcholinesterase in zebrafish (Danio rerio).

Several studies have indicated that hospital effluents can produce genotoxic and mutagenic effects, cytotoxicity, hematological and histological alterations, embryotoxicity, and oxidative stress in diverse water organisms, but research on the neurotoxic effects hospital wastewater materials can generate in fish is still scarce. To fill the above-described knowledge gap, this study aimed to determine whether the exposure of adult zebrafish (Danio rerio) to several proportions (0.1%, 2.5%, 3.5%) of a hospital effluent can disrupt behavior or impair redox status and acetylcholinesterase content in the brain. After 96 h of exposure to the effluent, we observed a decrease in total distance traveled and an increase in frozen time compared to the control group. Moreover, we also observed a significant increase in the levels of reactive oxygen species in the brains of the fish, especially in hydroperoxide and protein carbonyl content, relative to the control group. Our results also demonstrated that hospital effluents significantly inhibited the activity of the AChE enzyme in the brains of the fish. Our Pearson correlation demonstrated that the response to acetylcholinesterase at the lowest proportions (0.1% and 2.5%) is positively related to the oxidative stress response and the behavioral changes observed. The cohort of our studies demonstrated that the exposure of adult zebrafish to a hospital effluent induced oxidative stress and decreased acetylcholinesterase activity in the brain of these freshwater organisms, which can lead to alterations in their behavior.

Chronic exposure to environmentally relevant concentrations of guanylurea induces neurotoxicity of Danio rerio adults.

Recent studies have shown guanylurea (GUA) alters the growth and development of fish, induces oxidative stress, and disrupts the levels and expression of several genes, metabolites, and proteins related to the overall fitness of fish. Nonetheless, up to date, no study has assessed the potential neurotoxic effects that GUA may induce in non-target organisms. To fill the current knowledge gaps about the effects of this metabolite in the central nervous system of fish, we aimed to determine whether or not environmentally relevant concentrations of this metabolite may disrupt the behavior, redox status, AChE activity in Danio rerio adults. In addition, we also meant to assess if 25, 50, and 200 µg/L of GUA can alter the expression of several antioxidant defenses-, apoptosis-, AMPK pathway-, and neuronal communication-related genes in the brain of fish exposed for four months to GUA. Our results demonstrated that chronic exposure to GUA altered the swimming behavior of D. rerio, as fish remained more time frozen and traveled less distance in the tank compared to the control group. Moreover, this metabolite significantly increased the levels of oxidative damage biomarkers and inhibited the activity of acetylcholinesterase of fish in a concentration-dependent manner. Concerning gene expression, environmentally relevant concentrations of GUA downregulated the expression GRID2IP, PCDH17, and PCDH19, but upregulated Nrf1, Nrf2, p53, BAX, CASP3, PRKAA1, PRKAA2, and APP in fish after four months of exposure. Collectively, we can conclude that GUA may alter the homeostasis of several essential brain biomarkers, generating anxiety-like behavior in fish.

Low concentrations of ciprofloxacin alone and in combination with paracetamol induce oxidative stress, upregulation of apoptotic-related genes, histological alterations in the liver, and genotoxicity in Danio rerio.

Nowadays, there are countless articles about the harmful effects of paracetamol (PCM) in non-target organisms. Nonetheless, information regarding the toxicity of ciprofloxacin (CPX) and the CPX-PCM mixture is still limited. Herein, we aimed to evaluate the hepatotoxic and genotoxic effects that ciprofloxacin alone and in combination with paracetamol may induce in Danio rerio adults. For this purpose, we exposed several D. rerio adults to three environmentally relevant concentrations of PCM (0.125, 0.250, and 0.500 µg/L), CPX (0.250, 0.500, and 1 µg/L), and their mixture (0.125 + 0.250, 0.250 + 0.500, and 0.500 + 1 µg/L) for 96 h. The blood samples showed CPX alone and in combination with PCM damaged the liver function of fish by increasing the serum levels of liver enzymes alanine aminotransferase and alkaline phosphatase. Moreover, our histopathological study demonstrated liver of fish suffered several tissue alterations, such as congestion, hyperemia, infiltration, sinusoidal dilatation, macrovascular fatty degeneration, and pyknotic nuclei after exposure to CPX alone and in combination with PCM. Concerning oxidative stress biomarkers and the expression of genes, we demonstrated that CPX and its mixture, with PCM, increased the levels of antioxidant enzymes and oxidative damage biomarkers and altered the expression of Nrf1, Nrf2, BAX, and CASP3, 6, 8, and 9 in the liver of fish. Last but not least, we demonstrated CPX alone and with PCM induced DNA damage via comet assay and increased the frequency of micronuclei in a concentration-dependent manner in fish. Overall, our results let us point out CPX, even at low concentrations, induces hepatotoxic effects in fish and that its combination with PCM has a negative synergic effect in the liver of this organism.