Inhibition of the Nrf2 signaling pathway involved in imidacloprid-induced liver fibrosis in Coturnix japonica.

Imidacloprid (IMI) is a kind of widely used neonicotinoid insecticide. However, the toxicity of IMI is not only applied to target pests but also causes serious negative effects on birds and other creatures. Our previous studies have shown that long-term exposure to IMI can induce liver fibrosis in quails. However, the specific mechanism of quail liver fibrosis induced by IMI is not completely clear. Accordingly, the purpose of this study is to further clarify the potential molecular mechanism of IMI-induced liver fibrosis in quails. Japanese quails (Coturnix japonica) were treated with/without IMI (intragastric administration with 6 mg/kg body weight) in the presence/absence of luteolin (Lut) (fed with 800 mg/kg) for 90 days. The results reveal that IMI can induce hepatic fibrosis, oxidative stress, fatty degeneration, inflammation, and the down-expression of nuclear factor-E2-related factor-2 (Nrf2). Furthermore, the treatment of Lut, a kind of Nrf2 activator, increased the expression of Nrf2 in livers and alleviated liver fibrosis in quails. Altogether, our study demonstrates that inhibition of the Nrf2 pathway is the key to liver fibrosis induced by IMI in quails. These results provide a new understanding for the study of the toxicity of IMI and a practical basis for the treatment of liver fibrosis caused by IMI.

Imidacloprid-induced liver fibrosis in quails via activation of the TGF-ß1/Smad pathway.

Imidacloprid (IMI) is one of the most frequently used neonicotinoid insecticide, and its potential toxicity and environmental hazards have gradually attracted people's attention. Liver fibrosis caused by long-term inflammation or oxidative stress can lead to cirrhosis and liver failure, even death. However, the mechanism of liver fibrosis induced by neonicotinoid insecticide remains unclear. This study investigates whether IMI could induce liver fibrosis in quails and a potential mechanism. Our study used a quail 90-day IMI-induced liver fibrosis model. The results showed that IMI induced histopathological lesions, oxidative stress, inflammation, fibrosis, and changes in nuclear factor-kappa B (NF-κB), nuclear factor-E2-related factor-2 (Nrf2), and transforming growth factor (TGF-ß1) levels. Furthermore, IMI enhanced the expression of liver fibrosis marker proteins, including collagen I, α-smooth muscle actin (α-SMA), and fibronectin 1 (FN-1), by activating the TGF-ß1/Smad signaling pathway. In conclusion, our study demonstrated that IMI exposure induces liver fibrosis via activation of the TGF-ß1/Smad signaling pathway in quails.

Role of A2B adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice.

BACKGROUND: Multi-walled carbon nanotube (MWCNT)-induced lung fibrosis leads to health concerns in human. However, the mechanisms underlying fibrosis pathogenesis remains unclear. The adenosine (ADO) is produced in response to injury and serves a detrimental role in lung fibrosis. In this study, we aimed to explore the ADO signaling in the progression of lung fibrosis induced by MWCNT. RESULTS: MWCNT exposure markedly increased A2B adenosine receptor (A2BAR) expression in the lungs and ADO level in bronchoalveolar lavage fluid, combined with elevation of blood neutrophils, collagen fiber deposition, and activation of myeloperoxidase (MPO) activity in the lungs. Furthermore, MWCNT exposure elicited an activation of transforming growth factor (TGF)-ß1 and follistatin-like 1 (Fstl1), leading to fibroblasts recruitment and differentiation into myofibroblasts in the lungs in an A2BAR-dependent manner. Conversely, treatment of the selective A2BAR antagonist CVT-6883 exhibited a significant reduction in levels of fibrosis mediators and efficiently decreased cytotoxicity and inflammatory in MWCNT treated mice. CONCLUSION: Our results reveal that accumulation of extracellular ADO promotes the process of the fibroblast-to-myofibroblast transition via A2BAR/TGF-ß1/Fstl1 signaling in MWCNT-induced lung fibrosis.

Dietary grape seed procyanidin extract protects against lead-induced heart injury in rats involving endoplasmic reticulum stress inhibition and AKT activation.

To investigate the protective role of grape seed procyanidin extract (GSPE) against lead-induced heart injury and the possible molecular mechanism associated with this event, Wistar rats were orally given GSPE (200 mg/kg) daily with or without lead acetate (PbA) (0.5 g/L) in drinking water for 56 d. GSPE attenuated oxidative stress, heart dysfunction, and lead accumulation in lead-exposed rat hearts. Meanwhile, GSPE inhibited the protein kinase RNA-like endoplasmic reticulum (ER) kinase/eukaryotic initiation factor 2α signaling pathway, and promoted protein kinase B (AKT) and glycogen synthase kinase 3ß phosphorylation altered by lead, and regulated lead-activated apoptosis and its related signaling pathway. This study suggests that dietary GSPE ameliorates lead-induced heart injury associated with ER stress inhibition and AKT activation. Dietary GSPE may be a protector against lead-induced heart injury and a novel therapy for lead exposure.

Protective effects of dietary luteolin against mercuric chloride-induced lung injury in mice: Involvement of AKT/Nrf2 and NF-κB pathways.

Food-derived compound luteolin possesses multiple pharmacological activities. Accordingly, we focused on exploring the protective effects of luteolin (100 mg/kg) against mercuric chloride (HgCl2) (5 mg/kg) stimulated lung injury and the molecular mechanisms of lung protection effects in mouse. The influence of luteolin on histologic changes, oxidative stress, proinflammatory cytokine production, neutrophil activation, and apoptosis were assayed in HgCl2-induced lung injury. Luteolin administration attenuated pulmonary histologic conditions and apoptotic change. The protective effects of luteolin might be attributed to the reduction of myeloperoxidase, inflammatory cytokines, malondialdehyde, and the increase of superoxide dismutase and glutathione. Luteolin promoted protein kinase B (AKT) phosphorylation and translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) into nucleus, and inhibited activation of nuclear factor kappa B (NF-κB) in HgCl2-induced lung injury. Taken together, dietary luteolin may be an effective candidate for treatment of HgCl2-induced lung injury by preventing NF-κB activation and activating AKT/Nrf2 pathway.