Molecular Mechanism of Aniline Induced Spleen Toxicity and Neuron Toxicity in Experimental Rat Exposure: A Review

摘要

Aniline exposure leads to neuron and spleen toxicity specifically and makes diverse neu-rological effects and sarcoma that is defined by splenomegaly, hyperplasia, and fibrosis and tumorsformation at the end. However, the molecular mechanism(s) of aniline-induced spleen toxicity isnot understood well, previous studies have represented that aniline exposure results in iron overloadand initiation of oxidativeitrosative disorder stress and oxidative damage to proteins, lipids andDNA subsequently, in the spleen. Elevated expression of cyclins, cyclin-dependent kinases (CDKs)and phosphorylation of pRB protein along with increases in A, B and CDK1 as a cell cycle regula-tory proteins cyclins, and reduce in CDK inhibitors (p21 and p27) could be critical in cellcycle regulation, which contributes to tumorigenic response after aniline exposure. Aniline-inducedsplenic toxicity is correlated to oxidative DNA damage and initiation of DNA glycosylases expres-sion (OGG1, NEIL1/2, NTH1, APE1 and PNK) for removal of oxidative DNA lesions in rat. Oxi-dative stress causes transcriptional up-regulation of fibrogenic/inflammatory factors (cytokines, IL-1, IL-6 and TNF-α) via induction of nuclear factor-kappa B, AP-1 and redox-sensitive transcriptionfactors, in aniline treated-rats. The upstream signalling events as phosphorylation of IκB kinases(IKKα and IKKβ) and mitogen-activated protein kinases (MAPKs) could potentially be the causesof activation of NF-κB and AP-1. All of these events could initiate a fibrogenic and/or tumorigenicresponse in the spleen. The spleen toxicity of aniline is studied more and the different mechanismsare suggested. This review summarizes those events following aniline exposure that induce spleentoxicity and neurotoxicity.