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Abstract Di-(2-ethylhexyl) phthalate (DEHP) in the environment and food chain may impact cerebrum development and neurobehavioral in humans and wildlife. However, it is unclear that DEHP exposure caused cerebral toxicity. This experiment used gavage to expose female quail to 0, 250, 500, and 1000 mg/kg BW/day for 45 days to assess the potential neurotoxicity of DEHP to the cerebrum. It can be observed that there will be obvious neurological abnormalities in the experiment. Cerebrum histological lesions can be observed with HE-staining. Detecting oxidative stress indices, Nrf2 pathway, and mitochondrial dynamics factor, by analyzing the results, these results were observed that DEHP exposure can cause damage to the cerebrum by causing oxidative stress and affecting the balance of mitochondrial dynamics. Nrf2-mediated defense is not activated by exposure to 250 mg/kg DEHP. Nrf2-mediated defense is activated but is not resistant to exposure to medium and high doses of DEHP (500 mg/kg; 1000 mg/kg). DEHP triggers cerebral mitochondrial dysfunction via modulating mitochondrial dynamics. Graphical abstract DEHP exposure causes cerebral toxicity. DEHP causes oxidative stress in the cerebrum. DEHP regulates oxidative stress by activating the Nrf2 defense response. DEHP exposure also triggers disruption of mitochondrial dynamics leading to mitochondrial damage leading to oxidative stress. Image 1 Highlights • DEHP induces the cerebral toxicity. • DEHP activates Nrf2-mediated antioxidant defense in the cerebrum. • DEHP induced cerebral toxicity via disrupting mitochondrial dynamics. • DEHP triggers mitochondrial dysfunction via modulating mitochondrial dynamics. [ABSTRACT FROM AUTHOR]

Abstract Atrazine (ATR) is a most used herbicide which is believed as a pivotal determinant of environmental nephrosis, but potential mechanism is still largely unclear. This study intends to reveal a novel mechanism of ATR-induced nephrotoxicity. Quail were treated with 0, 50, 250 and 500 mg ATR/kg/d by oral gavage for 45 days. Kidney coefficient was decreased, biochemical and morphologic indices reflecting the kidney injury were significantly increased in ATR-exposed quail. ATR exposure upregulated the expression of proapoptotic factors (Bax, Caspase 3 and FasL) and downregulated antiapoptotic factor (Bcl-2). Notably, cristae of mitochondria decreased, mitochondrial malformation and mitochondrial vacuolar degeneration were observed in ATR-exposed quail. ATR induced the disorder of mitochondrial function related factors expressions and promoted oxidative damage. Furthermore, ATR induced toxicities in the expression of Nrf2 and Nrf2-target genes. In conclusion, ATR altered the microstructure and function of quail kidney. ATR induced renal damage via causing mitochondrial dysfunction, influencing mitochondrial function related genes expression, modulating Nrf2 signaling pathway. This study suggested ATR induced the nephrotoxicity via disturbing the transcription of mitochondrial function related factors and Nrf2 signaling pathway. Graphical abstract Graphical abstract illustrating the proposed mechanism by ATR-induced nephrotoxicity in quail. Nrf2 signaling pathway was blocked by ATR in kidney of quail. Mitochondria in quail kidney were the target organelles of ATR induced nephrotoxicity. ATR damaged mitochondrial function and morphology. It is deduced that ATR-induced nephrotoxicity is associated with mitochondrial dysfunction and interruption of Nrf2 signaling pathway. Image 1 Highlights • ATR decreased kidney coefficient, impaired histology and function of kidney. • ATR disturbed mitochondrial structure and function related genes expression. • ATR exposure stimulated apoptosis and oxidative stress. • ATR induced variation of Nrf2 signaling pathway and antioxidant response. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is a widely used herbicide with biologically toxic effects that can lead to neurotoxicity. Lycopene (LYC) is an antioxidant with chemoprotective properties. However, little know about the mechanisms of preventative interventions about LYC alleviated ATR-induced neurotoxicity. Male mice were treated with distilled water (C), 5 mg/kg BW/day LYC (L), 50 and 200 mg/kg BW/day ATR (A1, A2), respectively and LYC + ATR (A1+L, A2+L). ATR promoted oxidative stress and inflammatory damage, as showed by the effects on MDA, H 2 O 2 , IL-6 and TNF-α accumulation, and IL-10, SOD, CAT and GSH depletion, which caused neuronal swelling and mitochondrial vacuolar degeneration. ATR disrupted the CYP450s balance via increasing contents of CYP450 and cytochrome B5, enhancing activities of NCR and ERND and activating NXRs and NXRs-related transcription factors. However, all these effects were reversed by LYC pretreatment. Collectively, these data indicated that LYC inhibited ATR-induced oxidative damage through modulating xenobiotic-sensing nuclear receptors and CYP450s. [Display omitted] • LYC inhibits ATR exposure-induces neurotoxicity. • LYC alleviates ATR exposure-induces AHR/PXR/CAR pathway responses. • LYC alleviates ATR-induces the CYP450 homeostasis disorders and CYPs transcription. • LYC alleviates ATR exposure triggers oxidative stress and inflammatory response. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) has been implicated in the pathogenesis of inflammation, myocardial infarction, angiocardiopathy, even cancers. However, it is unknown that Cd-induced cardiac toxicity through Nrf2-mediate antioxidant defense and Cytochrome P450 (CYP450) system. To ascertain the chemoprevention of Cd-induced cardiac toxicity, total 60 newborn chicks were fed with different doses of Cd (0 mg/kg, 35 mg/kg and 70 mg/kg) for a period of 90 days feed administration. Results indicated Cd exposure caused cardiac histopathology changed and functions abnormal, induced NOS activities raised and cardiac inflammation, triggering inflammation factors (IL-6, IL-8, TNF-α, and NF-κb) upregulation and inhabitation of IL-10. Cd caused increase of total CYP450 and Cytochrome b 5 (Cyt b 5) contents, while erythromycin N-demethylase (ERND), aminopyrin N-demethylase (APND), aniline-4-hydeoxylase (AH) and NADPH-cytochrome c reductase (NCR) indicated opposite situations with different degrees of reduction in microsomes. The mRNA level of most CYP450s isoforms (CYP1A1, CYP1A2, CYP1A5, CYP1B1, CYP2C18, CYP2C45, CYP3A4, CYP3A7 and CYP3A9) were significantly increase but CYP2D6 expression level changed not obvious. Furthermore, Cd treatment caused increased the peroxidation product (MDA) and H 2 O 2 over accumulation, the decreased of T-AOC accompanied by decreased activity of antioxidant enzymes (T-SOD, GST and GPX). Over accumulation of Cd lead to oxidative stress and activated Nrf2 signal pathway through upregulating pivotal target genes (HO-1, NQO1, GCLC, GCLM and SOD). These findings suggested Cd exposure caused cardiotoxicity through CYP450s enzymes homeostasis disturbance and Nrf2-mediated oxidative stress signal pathways defense. These results may provide new evidence on molecular mechanism of Cd-induced cardiac toxicity. Cadmium (Cd) enters the heart through cell membranes and disrupts the metabolic system. Findings from the present study provide new evidence that Cd exposure affects the modulation of Cytochrome P450 Systems and Nrf2 mediated antioxidant defense in the heart. Cd exposure resulted in oxidative stress via disrupting the homeostasis of CYP450s, activating Nrf2 signaling. All data supplied in the present study contribute to broadening knowledge on the mechanisms of Cd-induced cardiotoxicity. Image 1 • Cadmium exposure caused cardiotoxicity. • Cadmium induced cardiac inflammation. • Cadmium disturbed the Cytochrome P450 homeostasis in heart. • Cadmium induced oxidative stress via affecting Nrf2 mediated antioxidant defense. [ABSTRACT FROM AUTHOR]