Fumonisins (FBs) are mycotoxins that are widely distributed in crops and feed, and ingestion of FBs -contaminated crops is harmful to animal health. Furthermore, it is unknown if Fumonisins B1 (FB1) can cause intestinal toxicity. To investigate FB1-induced intestinal toxicity, mice were treated with 0 or 5 mg/kg FB1 by gavage administration for 42 days. Histopathology indicated that FB1 exposure caused proliferation of intestinal epithelial cells, intestinal villi and epithelial layer shedding, intestinal gland atrophy, and necrosis. Notably, FB1 interfered with nuclear xenobiotic receptors (NXR) homeostasis by regulating the level of aryl hydrocarbon receptor (AHR), constitutive androstane receptor (CAR), pregnane X receptor (PXR) and downstream target genes (CYP450s). Moreover, abnormal expression of inflammatory cytokines (IL-1β, IL-2, IL-4, IL-10, and TNF-α) indicated the occurrence of inflammation. The present study provides new insights regarding the mechanism of FB1-induced intestinal toxicity through activating the NXR system and by triggering inflammatory responses in the intestinal tract in mice.

In our study, Bufo gargarizans (B. gargarizans) larvae were exposed to control, 0.5, 5, 10 and 50 mg/L of NaF from Gs 26 to 42. At Gs 42, we evaluated the changes of liver histology and the mRNA levels of target genes in liver. In addition, we also examined the composition and content of fatty acids. Histological analysis revealed that fluoride caused liver injury, such as the increase of number of melanomacrophage centres, atrophy of nucleus, dilation of bile canaliculus, and decrease of quantity, degradation and deposition of lipid droplets. The results of RT-qPCR indicated that exposure to 5, 10 and 50 mg/L of NaF significantly decreased the transcript levels of genes related to fatty acid synthesis (FASN, FAE, MECR, KAR and TECR) in liver. Besides, mRNA expression of genes involved in fatty acid β-oxidation (ECHS1, HADHA, SCP2, CPT2, ACAA1 and ACAA2) and oxidative stress (SOD, GPx, MICU1 and HSP90) was significantly downregulated in 0.5, 5, 10 and 50 mg/L of NaF treatment groups. Also, in the relative expression of genes associated with synthesis and secretion of bile acid, BSEP significantly increased at 0.5, 5 and 50 mg/L of NaF while HSD3B7 significantly reduced in 0.5, 5, 10 and 50 mg/L of NaF. Finally, the fatty acid extraction and GC-MS analysis showed that the content of saturated fatty acids (SFAs) was decreased and the content of polyunsaturated fatty acids (PUFAs) was increased in all fluoride treatment groups. Taken together, the present results indicated that fluoride-induced the histological alterations of liver might be linked to the disorder of lipid metabolism, oxidative damage.

Pyrene (Pyr), a widely used tetracyclic aromatic hydrocarbon, enters soil in large quantities and causes environmental pollution due to its production and mining. In order to systematically study the biotoxicity of pyrene to model organisms Eisenia fetida in soil, experiments were carried out from four dimensions: animal, tissue, cell and molecule. Experimental results proved that the mortality rate increased with increasing concentration and time of exposure to pyrene, while the mean body weight and spawning rate decreased. Meanwhile, when the pyrene concentration reached 900 mg/kg, the seminal vesicle and longitudinal muscle of the earthworm showed obvious atrophy. Experimental results at the cellular level showed that pyrene induced cell membrane damage and Ca²⁺ influx triggered mitochondrial membrane depolarization and a surge in ROS levels. Oxidative stress causes damage to proteins and lipids and DNA inside cells. When the mortality rate was 91.67 %, the Olive Tail Movement (OTM) of the comet experiment reached 15. The results of molecular level tests showed that pyrene inhibited the activity of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) mainly by changing the microenvironment and secondary structure of amino acid Tyr 108. The weakened function of direct antioxidant enzymes may be the root cause of the excessive increase of reactive oxygen species (ROS) in cells. The systematic approach used in this study enriches the network of toxic pathways in toxicological studies, and basic data on the biological toxicity of pyrene can provide support for future soil contamination detection.

Fluoride is a well-known compound for its usefulness in healing dental caries. Similarly, fluoride is also known for its toxicity to various tissues in animals and humans. It causes skeletal fluorosis leading to osteoporosis of the bones. We hypothesized that when bones are affected by fluoride, the skeletal muscles are also likely to be affected by underlying molecular events involving myogenic differentiation. Murine myoblasts C2C12 were cultured in differentiation media with or without NaF (1 ppm-5 ppm) for four days. The effects of NaF on myoblasts and myotubes when exposed to low (1.5 ppm) and high concentration (5 ppm) were assessed based on the proliferation, alteration in gene expression, ROS production, and production of inflammatory cytokines. Changes based on morphology, multinucleated myotube formation, expression of MyHC1 and signaling pathways were also investigated. Concentrations of NaF tested had no effects on cell viability. NaF at low concentration (1.5 ppm) caused myoblast proliferation and when subjected to myogenic differentiation it induced hypertrophy of the myotubes by activating the IGF-1/AKT pathway. NaF at higher concentration (5 ppm), significantly inhibited myotube formation, increased skeletal muscle catabolism, generated reactive oxygen species (ROS) and inflammatory cytokines (TNF-α and IL-6) in C2C12 cells. NaF also enhanced the production of muscle atrophy-related genes, myostatin, and atrogin-1. The data suggest that NaF at low concentration can be used as muscle enhancing factor (hypertrophy), and at higher concentration, it accelerates skeletal muscle atrophy by activating the ubiquitin-proteosome pathway.

Di-2-ethylhexyl phthalate (DEHP) has been widely used as a plasticizer in industry. DEHP can cause testicular atrophy, yet the exact mechanism remains unclear. In this study, male mice were intragastrically (i.g.) administered with 0, 100, 200 or 400 mg DEHP/kg/day for 21 days. We found that DEHP caused disintegration of the germinal epithelium and decreased sperm density in the epididymis. Furthermore, there was a significant increase in the levels of cleaved Caspase-8, cleaved Caspase-3 and Bax proteins and a decrease in Bcl2 protein. The results indicated that DEHP could induce apoptosis of the testis tissue. Meanwhile, DEHP significantly induced autophagy in the testis tissues with increases in LC3-II, Atg5 and Beclin-1 proteins. The serum testosterone concentration decreased in the DEHP-treated group, implying that DEHP might lead to Leydig cell damage. Furthermore, oxidative stress was induced by DEHP in the testis. To further investigate the potential mechanism, mouse TM3 Leydig cells were treated with 0–80 μM DEHP for 48 h. DEHP significantly inhibited cell viability and induced cell apoptosis. Oxidative stress was involved in DEHP-induced apoptosis as N-Acetyl-L-cysteine (NAC), an inhibitor of oxidative stress, could rescue the inhibition of cell viability and induction of apoptosis by DEHP. Similar to the in vivo findings, DEHP could also induce cell autophagy. However, inhibition of autophagy by 3-Methyladenine (3-MA) significantly increased cell viability and inhibited apoptosis. Taken together, oxidative stress was involved in DEHP-induced apoptosis and autophagy of mouse TM3 Leydig cells, and autophagy might play a cytotoxic role in DEHP-induced cell apoptosis.

As an emerging contaminant, 1-H-benzotriazole (1H-BTR) has been detected in the engineered and natural aquatic environments, which usually coexists with heavy metals and causes combined pollution. In the present study, wild-type and transgenic zebrafish Danio rerio were used to explore the acute toxicity as well as the single and joint hepatotoxicity of cadmium (Cd) and 1H-BTR. Although the acute toxicity of 1H-BTR to zebrafish was low, increased expression of liver-specific fatty acid binding protein was observed in transgenic zebrafish when the embryos were exposed to 5.0 μM of 1H-BTR for 30 days. Besides, co-exposure to 1H-BTR not only reduced the acute toxic effects induced by Cd, but also alleviated the Cd-induced liver atrophy in transgenic fish. Correspondingly, effects of combined exposure to 1H-BTR on the Cd-induced expressions of several signal pathway-related genes and superoxide dismutase and glutathione-s-transferase proteins were studied. Based on the determination of Cd bioaccumulation in fish and the complexing stability constant (β) of Cd-BTR complex in solution, the detoxification mechanism of co-existing 1H-BTR on Cd to the zebrafish was discussed.

The toxicity of carbaryl, tebufenpyrad, cypermethrin and permethrin was evaluated in European sea bass Dicentrarchus labrax during the embryonic and larval development using six different concentrations per chemical. The order of the toxicity effectiveness was carbaryl > tebufenpyrad > cypermethrin > permethrin. The larvae were more sensitive to all tested chemicals than embryos. The LC50 of carbaryl, tebufenpyrad, cypermethrin and permethrin was determined as 13.88, 43.96, 92 and 142 ppm and 9.27, 25.67, 48.4 and 72.7 ppm in embryo and larvae, respectively. Furthermore, the tested pesticides exhibited teratogenic effects on D. labrax embryo-larval stages. The observed malformations were coagulation, no spherical egg, unhatched egg, pericardial oedemata, yolk oedemata, lordosis, kyphosis, scoliosis, no eye, cranial deformation and body atrophy. Malformations were induced with 0.5 ppm carbaryl, 10 ppm tebufenpyrad and 50 ppm cypermethrin and permethrin; the highest rates of malformation were noted with 16 ppm carbaryl, 160 ppm tebufenpyrad, 400 ppm cypermethrin and 400 ppm permethrin as 34.5%, 28%, 17.5% and 16%, respectively. A positive correlation between the incidence of malformation and the increase of pesticide concentration was established.

Repeated deposition of copper oxide nanoparticles (CuO-NPs) into aquatic systems makes them a global threat since the NPs accumulate in various organs of the fish particularly skeletal muscle. In the present study, adult zebrafish were exposed to different concentrations of CuO-NPs (1 and 3 mg/L) for a period of 30 days. The status of functional markers (acetylcholinesterase, creatine kinase-MB, and lactate dehydrogenase) and oxidative stress markers (oxidants and antioxidants) were analyzed. The histological changes in muscle were studied followed by the immunohistochemistry expression for catalase. Further, the expression of myoD, myogenin, pax7, β-actin, and desmin was examined by semi-quantitative reverse transcriptase polymerase chain reaction. The results indicated that chronic exposure to CuO-NPs causes muscular damage as evidenced by elevated levels of functional markers. There was a significant increase in the oxidants with reduction in the antioxidant levels, implying that the antioxidant enzymes were unable to scavenge the free radicals induced by the CuO-NPs. The histopathological analysis showed degeneration and atrophy in the treated groups confirming muscle damage. The immunohistochemical catalase expression in the muscle was reduced in the treated groups further supporting the evidence that the antioxidant has suffered a decline. The altered gene expression indicates skeletal muscle damage due to the CuO-NPs exposure. Overall, the data suggest that chronic exposure to CuO-NPs caused muscular toxicity which may lead to muscle degeneration in adult zebrafish.

Phthalates, plasticizing chemicals, are top-rated environmental contaminants. Diethyl phthalate (DEP), a chief member of this family, was declared a potent endocrine disruptor and carcinogen in animals and humans. The current study was designed to explore the probable reproductive damage induced by DEP and the therapeutic efficacy of raw honey in male albino mice. Four-week-old 50 male mice were randomized equally in five groups, as control (C) received 0.1 ml distilled water; vehicle control (VC) received corn oil (0.1 ml/mouse); DEP (3mg/g/BW) dissolved in corn oil; honey control (HC) administered with honey (0.2 mg/g/day); and phthalate plus honey (P+H) administered with DEP and honey (3mg and 0.2 mg/g/BW/day respectively). Mice were treated through oral gavage for 54 days routinely, acclimatized for 6 days, and dissected. In the first instance, the antioxidant potential and total phenolic contents (TPC) of honey were analyzed through ferric reducing antioxidant power (FRAP) assay and Folin-Ciocalteu assay to confirm the antioxidant capacity of honey. The morphological, morphometric, histological, micrometric, sperm count, and hormonal analyses, and antioxidant capacity test in tissue homogenates were conducted by using tissues (testis, epididymis) and blood samples of mice. Mice exposed to DEP have a significant increase in body weight, LH level, and seminiferous tubule lumen diameter and decrease in the gonado-somatic index, testosterone level, sperm count, and seminiferous tubule diameter. Additionally, histopathology of testes showed interstitial space dilations, exfoliations, Leydig cell atrophy, germ cell degenerations, and spermatid retention in DEP-exposed testes sections. However, concomitant use of honey and DEP had shown a significant improvement in histopathological lesions, steroid hormone levels, and healthy sperm count. By these results, it is concluded that honey possessed antioxidant potential that can efficiently protect DEP-induced anomalies in male mice.

To explore the mechanism of renal toxicity induced by florfenicol (FFC), 120 chicks were randomly divided into 6 groups, 20 in each group. Except for the control group, different doses of FFC (0.15 g/L, 0.3 g/L, 0.6 g/L, 1.2 g/L, and 1.8 g/L) were added to drinking water in the other 5 groups. Five days later, blood was collected from the vein under the wing, and the complete kidneys were obtained as soon as possible, then tested the experimental indicators. The results showed that compared with control group, all doses of FFC significantly reduced the average weight gain of chicks (P < 0.05 or P < 0.01). Except for the 0.15 g/L FFC group, kidney index of chicks in the other doses of FFC groups were significantly increased (P < 0.05 or P < 0.01). The kidney tissues in all FFC groups showed obvious damage, deformities, cell atrophy, and cell gap enlargement. In addition, all doses of FFC significantly increased the contents of uric acid (UA), blood urea nitrogen (BUN), creatinine (CRE) in serum, and malondialdehyde (MDA) in renal tissue (P < 0.05 or P < 0.01), but significantly reduced the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in renal tissue (P < 0.05 or P < 0.01). FFC significantly inhibited the mRNA and protein expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase-1 (NQO-1), and increased the mRNA and protein expression levels of p53, Caspase-3, and Caspase-6 (P < 0.05 or P < 0.01). The apoptotic rate of renal cells in all doses of FFC groups increased significantly (P < 0.05 or P < 0.01). It was concluded that FFC had a certain degree of nephrotoxicity, and with the increase of FFC concentration, the kidney injury of chicks became more and more serious. FFC promoted oxidative stress response in kidney of chicks by inhibiting the expression of related factors in Nrf2-ARE pathway. Moreover, the expression of pro-apoptotic factors was upregulated to improve the apoptosis rate of renal cells, which resulted in excessive apoptosis of renal cells and seriously affected the kidney function of chicks.