Cytokine gene expression and activation of NF-κB in aniline-induced splenic toxicity

Wang, Jianling; Kannan, Subburaj; Li, Hui; Khan, M. Firoze

doi:10.1016/j.taap.2004.07.012

Cited by 27 publications

(37 citation statements)

References 38 publications

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“…Freshly isolated splenocytes were used for the nuclear protein extraction (Wang et al, 2005;Khan et al, 2006). Nuclear protein extracts (10 µg) from control or aniline-treated splenocytes were incubated with an oligonucleotide containing the NF-κB or p-c-Jun consensus binding site bound to 96-well microtiter plate.…”

Section: Quantitation Of Nf-κb and Ap-1 Activation In The Splenocytesmentioning

confidence: 99%

“…RNA isolation-Total RNA was isolated from spleen tissues using TRIZOL reagent (Life Technologies, New York, NY) as per manufacturer's instructions (Wang et al, 2005). To eliminate contaminating genomic DNA, RNA preparation was treated with RNase free DNase I (DNA-free kit, Ambion, Austin, TX).…”

Section: Rna Isolation and Quantitation Of Cytokine Mrnasmentioning

confidence: 99%

“…Real-time PCR: SYBR Green detection and Data analysis-First-strand cDNA was prepared from isolated RNA by using SuperScript First-Strand Synthesis Kit (Invitrogen, Carisbad, CA) described earlier (Wang et al, 2005). Quantitative real-time PCR employing a two-step cycling protocol (denaturation and annealing/extension) was carried out using Smart Cycler System, and using primers described previously (Wang et al, 2005).…”

Section: Rna Isolation and Quantitation Of Cytokine Mrnasmentioning

confidence: 99%

“…Quantitative real-time PCR employing a two-step cycling protocol (denaturation and annealing/extension) was carried out using Smart Cycler System, and using primers described previously (Wang et al, 2005). For each cDNA sample, parallel reactions were performed in triplicate for the detection of 18 S, rat IL-1α, rat IL-6 and rat TNFα in a reaction sample volume of 25 µl.…”

Section: Rna Isolation and Quantitation Of Cytokine Mrnasmentioning

confidence: 99%

“…In fact, aniline-induced splenic toxicity could be largely attributed to iron overload (increases in both total and free iron) as iron-induced oxidative and nitrosative stress in the spleen causes increased lipid peroxidation, protein oxidation, DNA oxidation and nitrotyrosine formation (Khan et al, 1997a(Khan et al, , 1997b(Khan et al, , 1999a(Khan et al, , 2003b(Khan et al, , 2003cWu et al, 2005). Earlier subchronic aniline exposure studies (related to fibrogenic response in the spleen) have also shown activation of redoxsensitive transcription factors (TFs) nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) in the spleen (Wang et al, 2005;Khan et al, 2006). However, status of these TFs and the possible mechanisms in their activation, especially the upstream signaling pathways, and consequences of their activation (downstream target genes) at an early stage which precedes fibrosis in the spleen are not known.…”

Section: Introductionmentioning

confidence: 99%

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Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline

Wang

Ansari

et al. 2008

Toxicology and Applied Pharmacology

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Aniline exposure causes toxicity to the spleen, which leads to a variety of sarcomas, and fibrosis appears to be an important preneoplastic lesion. However, early molecular mechanisms in anilineinduced toxicity to the spleen are not known. Previously, we have shown that aniline exposure results in iron overload and induction of oxidative stress in the spleen, which can cause transcriptional upregulation of fibrogenic/inflammatory cytokines via activation of oxidative stress (OS)-responsive signaling pathways. To test this mechanism, male SD rats were treated with aniline (1 mmol/kg/day via gavage) for 7 days, an experimental condition that precedes the appearance of fibrosis. Significant increases in both NF-κB and AP-1 binding activity was observed in the nuclear extracts of splenocytes from aniline-treated rats as determined by ELISAs, and supported by Western blot data showing increases in p-IκBα, p-p65 and p-c-Jun. To understand the upstream signaling events which could account for the activation of NF-κB and AP-1, phosphorylation patterns of IκB kinases (IKKα and IKKβ) and mitogen-activated protein kinases (MAPKs) were pursued. Our data showed remarkable increases in both p-IKKα and p-IKKβ in the splenocytes from aniline-treated rats, suggesting their role in the phosphorylation of both IκBα and p65 subunits. Furthermore, aniline exposure led to activation of all three classes of MAPKs, as evident from increased phosphorylation of extracellularsignal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK1/2) and p38 MAPKs, which could potentially contribute to the observed activation of both AP-1 and NF-κB. Activation of upstream signaling molecules was also associated with simultaneous increases in gene transcription of cytokines IL-1, IL-6 and TNF-α. The observed sequence of events following aniline exposure could initiate a fibrogenic and/or tumorigenic response in the spleen.

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Section: Quantitation Of Nf-κb and Ap-1 Activation In The Splenocytesmentioning

confidence: 99%

Section: Rna Isolation and Quantitation Of Cytokine Mrnasmentioning

confidence: 99%

Section: Rna Isolation and Quantitation Of Cytokine Mrnasmentioning

confidence: 99%

Section: Rna Isolation and Quantitation Of Cytokine Mrnasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline

Wang

Ansari

et al. 2008

Toxicology and Applied Pharmacology

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Aromatic Nitro and Amino Compounds

Johnson¹

2023

Patty's Toxicology

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Aromatic nitro and amino compounds have various commercial, governmental, and public applications. Their uses include manufacturing of dyes, pesticides, drugs, and explosives. These substances are typically considered high‐nitrogen compounds and as such share many of the same chemical and biological properties. Many have amines and/or nitrate groups on the ring and because of this exhibit properties where they are not highly water or lipid soluble and many tend to form crystals. When released to the environment, nitrate‐containing moieties are often reduced to amines by bacteria in wet soils and sediments. Acute effects typically target the nervous system; however, sublethal effects from repetitive exposures include anemia, methemoglobinemia, and often male reproductive effects. Cyanosis has been described from relatively high repetitive exposures. Oral exposures can affect the liver. Many are absorbed through the skin where dermal exposures can significantly contribute to systemic dose. Skin sensitization and irritation have been observed from exposure to some compounds. Many are eliminated via the urine; however, conjugated metabolites can be eliminated via the feces. Nitroso metabolites are suspected as having influence in observation of cancer, particularly in the bladder. Other similar nitramine compounds are also briefly described.

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Aromatic Amino and Nitro–Amino Compounds and Their Halogenated Derivatives

Woo¹,

Lai²

2012

Patty's Toxicology

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Aromatic amines are organic compounds that contain at least one amino group attached directly to an aryl moiety. Aromatic amines represent one of the most important classes of industrial and environmental chemicals. Many aromatic amines have been shown to be potent carcinogens, mutagens, skin sensitizers, and/or hematotoxicants capable of inducing methemoglobinemia. Since the introduction of substituted anilines and naphthylamines as intermediates for the manufacture of azo dyes in the mid‐1800s, aromatic amines have found numerous uses in various industries. Substantial worker exposure to aromatic amines with subsequent induction of bladder cancer occurred before preventive measures were instituted. Beyond occupational exposure, humans may also be exposed to aromatic amines through environmental sources. At least three carcinogenic aromatic amines (4‐aminobiphenyl, 2‐naphthylamine, and o ‐toluidine) have been detected in cigarette smoke. Many commonly used pharmaceuticals contain or are aromatic amines. Owing to their hazard potential, aromatic amines have been the subject of many biomonitoring studies, making them model compounds in molecular dosimetry and epidemiology studies. Since extensive information is available on the metabolic pathways and, to a lesser extent, the mechanism(s) of action, aromatic amines have also become targets for genetic polymorphism studies with ultimate goals of identifying susceptible subpopulations and designing of strategies for cancer prevention and intervention. The multifaceted interest in aromatic amines has continued to attract a tremendous amount of scientific studies and attention. Since the publication of the previous edition of Patty's on aromatic amines, many reviews and important research articles on aromatic amines and halogenated nitroaromatics have been published. In addition, a number of heterocyclic aromatic amines have attracted increasing attention as carcinogens of environmental significance. In this chapter, we present an overview of the aromatic amine class as a whole with emphasis on recent studies, followed by an updated description on individual chemicals grouped into eight subgroups of structurally related compounds.

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Cytokine gene expression and activation of NF-κB in aniline-induced splenic toxicity

Cited by 27 publications

References 38 publications

Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline

Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline

Aromatic Nitro and Amino Compounds

Aromatic Amino and Nitro–Amino Compounds and Their Halogenated Derivatives

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