No abstract

With the progress of nanotechnology, nano nickel oxide (NiO) has been extensively used as sensors, battery electrodes, catalysts, and cosmetics. Previous researches verified that nano NiO could exert pulmonary toxicity, but its mechanism was unclear. To shed light upon this, the role of nuclear factor-κB (NF-κB) activation and Th1/Th2 imbalance were to explore in pulmonary damage induced by nano NiO. Male Wistar rats were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg kg ) and micro NiO group (0.024 mg kg ) and treated by intratracheal instillation twice a week for 6 weeks. The results showed that the abnormal changes induced by nano NiO were found on indicators of nitrative stress (NO, TNOS, and iNOS), inflammatory cytokines (TNF-α, IL-2, and IL-10) and cytokine-induced neutrophil chemoattractants (CINC-1, CINC-2αβ, and CINC-3) in lung tissue. In addition, nano NiO instillation induced the upregulated mRNA and protein expression of NF-κB, inhibitor of κB kinase-α (IKK-α) and nuclear factor-inducing kinase (NIK). The protein content of GATA-3 increased as well as T-bet decreased in nano NiO groups, and the ratio of T-bet/GATA-3, as a key evaluation indicator of Th1/Th2 balance, was lower than the control group. The findings indicated that nano NiO could enhance the nitrative stress and inflammatory response in lung tissue, and its mechanism was related to the NF-κB activation and Th1/Th2 imbalance. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1354-1362, 2017.

No abstract

Studies have demonstrated that nano NiO could induce liver toxicity in rats, but its mechanism remains unclear. This study aimed to explore the role of the NF-κB signaling pathway in rat liver toxicity after nano NiO exposure. Male Wistar rats were exposed to nano NiO (0.015, 0.06 and 0.24 mg per kg b.w.) and micro NiO (0.24 mg per kg b.w.) by intratracheal instillation twice a week for 6 weeks. To investigate the liver toxicity induced by nano NiO, the indicators of liver function and inflammatory response were detected, and the histopathological changes were observed. The levels of NF-κB signaling pathway related gene and protein expression were examined using RT-qPCR and western blot techniques in the liver tissue. The results showed that the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyltranspeptidase (GGT) increased after nano NiO exposure. Cellular edema, hepatic sinus disappearance, and neutrophil and lymphocyte infiltration were observed. Nano NiO increased the concentrations of pro-inflammatory cytokines (IL-1β and IL-6), but decreased the levels of anti-inflammatory cytokines (IL-4 and IL-10). It also induced the upregulation of TNF-α, NF-κB-inducible kinase (NIK), IκB kinase alpha (IKK-α) and NF-κB mRNA, while inducing the downregulation of the inhibitor kappa B (IκB) alpha. In addition, we found that the protein content of NIK, IKK-α, p-IKK-α, p-IκB-α and NF-κB was elevated, whereas that of IκB-α was reduced. The results indicated that the NF-κB signaling pathway played an important role in rat liver toxicity induced by nano NiO.

Nickel oxide nanoparticles (nano NiO) could induce hepatocyte apoptosis, while its potential mechanisms are unclear. This study aimed to explore the role of endoplasmic reticulum (ER) stress pathways in hepatocyte apoptosis induced by nano NiO. Male Wistar rats were administrated with nano NiO (0.015, 0.06, and 0.24 mg/kg b.w.) and micro NiO (0.24 mg/kg b.w.) by intratracheal instillation twice a week for 6 weeks. We measured the hepatocyte apoptosis levels by TdT-mediated dUTP nick-end labeling (TUNEL) staining, ER stress related gene and protein expression levels in rat liver. The results showed that the TUNEL positive cells increased after exposure nano NiO, hinting hepatocyte apoptosis. The up-regulated gene and protein levels of 78 kD glucose regulated protein and CCAAT/enhancer binding protein homologous protein suggested that nano NiO triggered ER stress. Nano NiO exposure contributed to the increased protein contents of inositol-requiring enzyme 1 (IRE-1)α, p-IRE-1α, X box protein-1S, pancreatic ER kinase (PERK), p-PERK, eukaryotic initiation factor-2 alpha (eIF-2α), p-eIF-2α, caspase-12, -9, and -3, implicating that nano NiO can activate the pathways of ER stress-mediated apoptosis. These findings indicate that the ER stress pathways may play an important role in hepatocyte apoptosis induced by nano NiO.

The aim of the present study was to explore the role of oxidative stress in liver toxicity induced by nickel oxide nanoparticles (nano‑NiO) in rats. Male Wistar rats received saline (control), nano‑NiO [0.015, 0.06 or 0.24 mg/kg body weight (b.w.)] or micro‑NiO (0.24 mg/kg b.w.) by intratracheal instilling twice a week for 6 weeks. Liver tissues were then collected and examined for biomarkers of nitrative and oxidative stress, as well as mRNA expression of heme oxygenase (HO)‑1 and metallothionein (MT)‑1. The results demonstrated that the NiO exposure groups had increased liver wet weight and coefficient to body weight, as well as liver pathological changes, evidenced as cellular edema, hepatic sinus disappeara-nce and binucleated hepatocytes. The activities of total nitric oxide synthase and inducible nitric oxide synthase, and the nitric oxide content, were increased in the 0.24 mg/kg nano‑NiO group compared with the control group. The MT‑1 mRNA expression levels were downregulated, while HO‑1 mRNA was upregulated in the 0.24 mg/kg nano‑NiO exposure group compared with the control group. In addition, abnormal changes of hydroxyl radical, lipid peroxidation, catalase, glutathione peroxidase, total superoxide dismutase and total antioxidative capacity were observed in the liver tissues of the 0.24 mg/kg nano‑NiO exposure group, compared with the control group. The present results therefore indicated that nano‑NiO‑induced liver toxicity may be associated with nitrative and oxidative stress in rats.

Nickel can induce apoptosis of testicular Leydig cells in mice, whereas the mechanisms remain unclear. In this study, we investigated the role of nickel-induced reactive oxygen species (ROS) generation in mitochondria and endoplasmic reticulum stress (ERS) mediated apoptosis pathways in rat Leydig cells. Fluorescent DCF and Annexin-V FITC/PI staining were performed to measure the production of ROS and apoptosis in Leydig cells. RT-qPCR and Western blot were conducted to analyze the key genes and proteins involved in mitochondria and ERS apoptotic pathways. The results showed that nickel sulfate induced ROS generation, consequently resulted in nucleolus deformation and apoptosis in testicular Leydig cells, which were then attenuated by ROS inhibitors of N-acetylcysteine (NAC) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). Nickel sulfate-triggered Leydig cells apoptosis via mitochondria and ERS pathways was characterized by the upregulated mRNA and proteins expression of Bak, cytochrome c, caspase 9, caspase 3, GRP78, GADD153, and caspase 12, which were inhibited by NAC and TEMPO respectively. The findings indicated that nickel-induced ROS generation was involved in apoptosis via mitochondria and ERS pathways in rat Leydig cells.

No abstract