Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-3 (of 3 Records) |
Query Trace: Aldinger J [original query] |
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ROS generation is involved in titanium dioxide nanoparticle-induced AP-1 activation through p38 MAPK and ERK pathways in JB6 cells
Kong L , Barber T , Aldinger J , Bowman L , Leonard S , Zhao J , Ding M . Environ Toxicol 2021 37 (2) 237-244 Titanium dioxide (TiO(2) ) is generally regarded as a nontoxic and nongenotoxic white mineral, which is mainly applied in the manufacture of paper, paint, plastic, sunscreen lotion and other products. Recently, TiO(2) nanoparticles (TiO(2) NPs) have been demonstrated to cause chronic inflammation and lung tumor formation in rats, which may be associated with the particle size of TiO(2) . Considering the important role of activator protein-1 (AP-1) in regulating multiple genes involved in the cell proliferation and inflammation and the induction of neoplastic transformation, we aimed to evaluate the potency of TiO(2) NPs (≤ 20 nm) on the activation of AP-1 signaling pathway and the generation of reactive oxygen species (ROS) in a mouse epidermal cell line, JB6 cells. MTT, electron spin resonance (ESR), AP-1 luciferase activity assay in vitro and in vivo, and Western blotting assay were used to clarify this problem. Our results indicated that TiO(2) NPs dose-dependently caused the hydroxyl radical (·OH) generation and sequentially increased the AP-1 activity in JB6 cells. Using AP-1-luciferase reporter transgenic mice models, an obvious increased AP-1 activity was detected in dermal tissue after exposure to TiO(2) NPs for 24 h. Interestingly, TiO(2) NPs increased the AP-1 activity via stimulating the expression of mitogen-activated protein kinases (MAPKs) family members, including extracellular signal-regulated protein kinases (ERKs), p38 kinase, and C-Jun N-terminal kinases (JNKs). Of note, the AP-1 activation induced by TiO(2) NPs could be blocked by specific inhibitors (SB203580, PD98059, and SP 600125, respectively) that inhibit ERKs and p38 kinase but not JNKs. These findings indicate that ROS generation is involved in TiO(2) NPs-induced AP-1 activation mediated by MAPKs signal pathway. |
The systemic toxicity of heavy metal mixtures in rats
Fiati Kenston SS , Su H , Li Z , Kong L , Wang Y , Song X , Gu Y , Barber T , Aldinger J , Hua Q , Li Z , Ding M , Zhao J , Lin X . Toxicol Res (Camb) 2018 7 (3) 396-407 To explore the health effects of multi-heavy metal exposure, Sprague Dawley (SD) rats were orally given one dose of heavy metal mixtures (HMMs). The eight most common detectable heavy metals in Ningbo area are zinc (Zn), copper (Cu), manganese (Mn), chromium (Cr), nickel (Ni), cadmium (Cd), lead (Pb) and mercury (Hg). In this study, mixtures of these eight heavy metals were prepared using the compounds zinc sulfate heptahydrate, cupric sulfate, manganese dichloride, potassium dichromate, nickel dichloride, cadmium dichloride, lead acetate, and methyl mercury chloride with ion mass proportions of 1070.0, 312.6, 173.1, 82.6, 30.0, 13.3, 6.6, and 1.0, respectively. The rats were randomly divided into four groups. Beside the control group, each rat received a corresponding dose of HMMs 215, 464 or 1000 mg per kg body weight (bwt), respectively. The rats were observed for 4 weeks. During the last week of observation, the Morris water maze test was used to investigate spatial learning and memory in the treated rats. The rats were exsanguinated under complete chloral hydrate anesthesia and organ coefficients were measured. Biochemical tests of blood and serum samples were carried out. The results showed abnormalities in the hematological system, decreased renal function, hepatic injury and disturbances in the electrolyte balance of the rats treated with a high dose of HMMs. Death of some rats was also observed. This paper analyzed how a one-time high dose oral administration of HMMs induced systemic toxicity. © 2018 The Royal Society of Chemistry. |
Joint toxicity of different heavy metal mixtures after a short-term oral repeated-administration in rats
Su H , Li Z , Fiati Kenston SS , Shi H , Wang Y , Song X , Gu Y , Barber T , Aldinger J , Zou B , Ding M , Zhao J , Lin X . Int J Environ Res Public Health 2017 14 (10) The systemic toxicity of different combinations of heavy metal mixtures (HMMs) was studied according to equivalent proportions of the eight most common detectable heavy metals found in fish consumption in the Ningbo area of China. The ion mass proportions of Zn, Cu, Mn, Cr, Ni, Cd, Pb, and Hg were 1070.0, 312.6, 173.1, 82.6, 30.0, 13.3, 6.6, and 1.0, respectively. In this study, 10 experimental groups were set as follows: M8 (Pb + Cd + Hg + Ni + Cu + Zn + Mn + Cr); M5 (Pb + Cd + Hg + Ni + Cr); M4A (Pb + Cd + Hg + Ni); M4B (Cu + Zn + Mn + Cr); M3 (Cu + Zn + Mn); Cr; Cu; Zn; Mn; and control. Sprague Dawley (SD) rats were orally treated with a single dose of each group every three days (10 times in total) for 34 days. After Morris water maze test, blood and tissue samples were collected to obtain biochemical, histopathological and western blot analysis. Results show abnormalities could be observed in different treatment groups, the M4B combination had the most significant change compared to all other groups. In conclusion, combination HMMs may have adverse effects on the hematologic, hepatic, renal and neurobehavioral function, and may also disturb electrolyte and lipid balance. Why M4B combination generated much higher toxic effects than any other combination mixtures or individual heavy metal needs to be further evaluated. |
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