Comparative Biochemistry and Physiology C-toxicology & Pharmacology最新文献

The intertidal organism Tegillarca granosa can survive under frequent hypoxia/reoxygenation (H/R) exposure. Sulfides as accompanying products in benthic hypoxic environments, may play an important regulatory role, but the mechanisms are not well understood. This article investigated the physiological and molecular changes of T. granosa after adding different concentrations of sulfides (0.1, 0.5, 1 mM) at 72 h into a 120-h exposure to hypoxia, as well as the recovery state of 24 h of reoxygenation. The results indicated that H/R stress induces ROS production and mild mitochondrial depolarization in clams, and sulfide can participate in its regulation. Among them, a low concentration of sulfide up-regulated glutathione content and alternative oxidase activity, maintained the stability of antioxidant enzymes, and up-regulated the expression of the survival genes XIAP/BCL-xl which mediate cell survival via the NFκB signaling pathway. High concentrations of sulfide had a significant inhibitory effect on the p38/MPAK pathway and inhibited intrinsic apoptosis caused by ROS accumulation during reoxygenation. Taken together, our study suggested that different concentrations of sulfides are involved in regulating the endogenous apoptosis of clams during H/R.

In this study, we focused on confirming the steroid hormone receptor-mediated endocrine-disrupting potential of the pyrethroid insecticide fenvalerate and unraveling the underlying mechanisms. Therefore, we assessed estrogen receptor-α (ERα)- and androgen receptor (AR)-mediated responses in vitro using a hormone response element-dependent transcription activation assay with a luciferase reporter following the Organization for Economic Cooperation and Development (OECD) test guidelines. We observed that fenvalerate acted as estrogen by inducing the translocation of cytosolic ERα to the nucleus via ERα dimerization, whereas it exhibited no AR-mediated androgen response element-dependent luciferase activity. Furthermore, we confirmed that fenvalerate-induced activation of ERα caused lipid accumulation, promoted in a fenvalerate-dependent manner in 3 T3-L1 adipocytes. Moreover, fenvalerate-induced lipid accumulation was inhibited in the presence of an ERα-selective antagonist, whereas it remained unaffected in the presence of a glucocorticoid receptor (GR)-specific inhibitor. In addition, fenvalerate was found to stimulate the expression of transcription factors that promote lipid accumulation in 3 T1-L1 adipocytes, and co-treatment with an ERα-selective antagonist suppressed adipogenic/ lipogenic transcription factors at both mRNA and protein levels. These findings suggest that fenvalerate exposure may lead to lipid accumulation by interfering with ERα activation-dependent processes, thus causing an ERα-mediated endocrine-disrupting effect.

Pesticides are widely used to control weeds and pests in agricultural settings but harm non-target aquatic organisms. In this study, our objective was to evaluate the effect of short-term exposure (one week) to environmentally relevant concentrations of pesticides mixture (low concentration: 0.4 μg/l atrazine, 0.5 μg/l Roundup®, and 0.5 μg/l 2,4-D; high concentration: 0.8 μg/l atrazine, 1 μg/l Roundup®, and 1 μg/l 2,4-D) on tissue architecture, body fluid conditions, and 3-nitrotyrosine protein (NTP) and Na⁺/K⁺-ATPase, expressions in tissues of American oyster (Crassostrea virginica) under controlled laboratory conditions. Histological analysis demonstrated the atrophy in the gills and digestive glands of oysters exposed to pesticides mixture. Periodic acid-Schiff (PAS) staining showed the number of hemocytes in connective tissue increased in low- and high-concentration pesticides exposure groups. However, pesticides treatment significantly (P < 0.05) decreased the amount of mucous secretion in the gills and digestive glands of oysters. The extrapallial fluid (i.e., body fluid) protein concentrations and glucose levels were dropped significantly (P < 0.05) in oysters exposed to high-concentration pesticides exposure groups. Moreover, immunohistochemical analysis showed significant upregulations of NTP and Na⁺/K⁺-ATPase expressions in the gills and digestive glands in pesticides exposure groups. Our results suggest that exposure to environmentally relevant pesticides mixture causes morphological changes in tissues and alters body fluid conditions and NTP and Na⁺/K⁺-ATPase expressions in tissues, which may lead to impaired physiological functions in oysters.

Plasticizers are considered as newly emerged contaminants. They are added to plastics to increase their flexibility and softness. Phthalate plasticizers including the Di-2-ethylhexyl phthalates (DEHP) are toxic and induce adverse effects on the different organization levels of the environment. In the current study, we investigated the potential toxicity of DEHP using Zebrafish as a biological model. Five ascending concentrations of DEHP were tested in embryos throughout 96 hpf: 0.0086, 0.086, 0.86, 8.6, and 86 mg/L. Embryotoxicity assessments revealed limited lethal effects on DEHP-exposed embryos, yet notable anticipation of the hatching process was observed at 48 hpf. Although DEHP showed negligible influence on the length and pericardial area of exposed embryos, it led to multiple bodily deformities. Gene expression analyses of key cardiogenic and inflammatory genes evidenced alterations in tbx20, bcl2, and il1b expression in Zebrafish embryos at 96 h post-fertilization. Results from the cardiac function analysis displayed that DEHP significantly affected the arterial pulse and linear velocity within the Posterior Cardinal Vein (PCV) of exposed fish. These findings strongly advance that even at low concentrations, DEHP can be considered as potential toxic agent, capable of inducing cardiotoxic effects.

Organophosphorus pesticides (OPs), such as chlorpyrifos (CPF), are the most commonly used pesticides worldwide. Considering that OPs will eventually enter aquatic ecosystems due to runoff from agricultural lands, accidental leakage, and other unforeseen emergencies, monitoring water pollution of those substances is crucial for environmental protection and public health. In this study, Japanese medaka (Oryzias latipes) were exposed to CPF (0.03, 0.06, and 0.12 mg/L) for 6 h, and the time-series variations in their locomotor behavior and vocal traits were investigated. Compared with that measured before exposure, significantly changed locomotor behavior and vocal traits in Japanese medaka exposed to CPF could be observed at 4 h after exposure and thereafter, and the pattern of behavioral changes depends on the CPF concentrations. Exposure to CPF also changed the frequency-sound pressure level curve of Japanese medaka at 6 h after exposure, especially at 0.12 mg/L. Moreover, CPF exposure could significantly inhibit the acetylcholinesterase (AChE) activity in the brains and eyes of medaka, which exhibited significant correlations with the variation of locomotor behavioral and vocal traits. Considering that inhibiting the AChE activity is the primary mechanism underlying the neurobehavioral toxicity of all OPs, our finding suggested that simultaneously monitoring changes in the locomotor behavioral and vocal traits has a high potential to reflect the pollution of organophosphorus substances.

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.

The chiral fungicide prothioconazole (PTZ) is extensively employed in agricultural practices, prompting serious concern due to its environmental impact. PTZ is prone to undergo metabolism, leading to the formation of chiral prothioconazole-desthio (dPTZ) in the environment. However, limited knowledge exists regarding its enantioselective behavior and toxicity towards invertebrate organisms in soil ecosystems. In this study, R-(-)- and S-(+)- PTZ enantiomers were individually synthesized, and their stereoselective toxicity effects on earthworms (E. foetida) were studied in artificial soil under environmentally relevant concentration exposures. The results showed a significant accumulation of dPTZ in earthworms, surpassing the levels of PTZ. Moreover, the concentration of S-(-)- dPTZ in earthworms was notably higher than that of R-(+)- dPTZ after exposure, reaching peak levels on day 14. Concurrently, oxidative stress induced by S-(+)- PTZ enantiomers in earthworms exhibited a substantial increase compared to R-(-)- enantiomers on day 14, indicating a higher ecological risk associated with the former in non-target organisms. Transcriptome analysis unveiled distinct impacts on earthworm physiology. S-(+)-PTZ exposure significantly affected energy metabolism, immune responses and digestive systems. In contrast, R-(-)-PTZ exposure influenced the synthesis of carbohydrates, proteins, and lipids. These insights contribute to understanding the complex interactions between PTZ enantiomers and soil-dwelling organisms, providing a scientific foundation for advancing the application of high efficiency, low toxicity PTZ monomer pesticides.

Aflatoxin B₁ (AFB₁) is highly toxic to the liver and can cause excessive production of mitochondrial reactive oxygen species (mtROS) in hepatocytes, leading to oxidative stress, inflammation, fibrosis, cirrhosis, and even liver cancer. The overproduction of mtROS can induce mitophagy, but whether mtROS and mitophagy are involved in the liver injury induced by AFB₁ in ducks remains unclear. In this study, we first demonstrated that overproduction of mtROS and mitophagy occurred during liver injury induced by AFB₁ exposure in ducks. Then, by inhibiting mtROS and mitophagy, we found that the damage caused by AFB₁ in ducks was significantly alleviated, and the overproduction of mtROS induced by AFB₁ exposure could mediate the occurrence of mitophagy. These results suggested that mtROS-mediated mitophagy is involved in AFB₁-induced duck liver injury, and they may be the prevention and treatment targets of AFB₁ hepatotoxicity.

Pyrimethanil is a persistent environmental pollutant that poses a significant threat to human health. In this review, we summarize the fungicidal mechanism of pyrimethanil and its toxicological effects on aquatic organisms and mammals, as well as its impact on growth and development as an endocrine disruptor. Additionally, we investigate the metabolism of pyrimethanil in mammals and its molecular mechanism in the occurrence of Alzheimer's disease. Furthermore, this review outlines the influence of climate change on the toxicity of pyrimethanil, emphasizing the need to consider the impact of mixtures of multiple compounds on human health. Finally, we propose several promising future directions for pyrimethanil research, believing that there is a better understanding of the interaction between pyrimethanil and organisms, as well as the development of techniques to remove pyrimethanil, may be the best approach to eliminating the threat posed by this compound.

Mollusks, including snails, possess two chambered hearts. The heart and cardiomyocytes of snails have many similarities with those of mammals. Also, the biophysics and pharmacology of Ca, K, and Na ion channels resemble. Similar to mammals, in mollusks, the ventricular cardiomyocytes and K channels are often studied, which are selectively sensitive to antagonists such as 4-AP, E-4031, and TEA. Since the physiological properties of the ventricular cardiac cells of snails are well characterized, the enzymatically dissociated atrial cardiomyocytes of Cornu aspersum (Müller, 1774) were studied using the whole-cell patch-clamp technique for detailed comparisons with mice, Mus musculus. The incubation of tissues in a solution simultaneously containing two enzymes, collagenase and papain, enabled the isolation of single cells. Recordings in the atrial cardiomyocytes of snails revealed outward K⁺ currents closely resembling those of the ventricle. The latter was consistent, whether the voltage ramp or steps and long or short pulses were used. Interestingly, under identical conditions, the current waveforms of atrial cardiomyocytes in snails were similar to those of mice left ventricles, albeit the kinetics and the absence of inward rectifier K channel (I_K1) activation. Therefore, the heart of mollusks could be used as a simple and accessible experimental model, particularly for pharmacology and toxicology studies.