Title:Molecular Mechanism of Aniline Induced Spleen Toxicity and Neuron Toxicity in Experimental Rat Exposure: A Review
Volume: 17
Issue: 3
Author(s): Pouran Makhdoumi, Hooshyar Hossini*, Ghulam Md Ashraf *Mojtaba Limoee
Affiliation:
- Research Center for Environmental Determinants of Health (RCEDH), School of Public Health, Kermanshah University of Medical Sciences, Kermanshah,Iran
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah,Saudi Arabia
Keywords:
Aniline, oxidative stress, neurotoxicity, spleen toxicity, neurology, pharmacology.
Abstract: Aniline exposure leads to neuron and spleen toxicity specifically and makes diverse neurological
effects and sarcoma that is defined by splenomegaly, hyperplasia, and fibrosis and tumors
formation at the end. However, the molecular mechanism(s) of aniline-induced spleen toxicity is
not understood well, previous studies have represented that aniline exposure results in iron overload
and initiation of oxidative/nitrosative disorder stress and oxidative damage to proteins, lipids and
DNA 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 regulatory
proteins cyclins, and reduce in CDK inhibitors (p21 and p27) could be critical in cell cycle
regulation, which contributes to tumorigenic response after aniline exposure. Aniline-induced
splenic toxicity is correlated to oxidative DNA damage and initiation of DNA glycosylases expression
(OGG1, NEIL1/2, NTH1, APE1 and PNK) for removal of oxidative DNA lesions in rat. Oxidative
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 transcription
factors, 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 causes
of activation of NF-κB and AP-1. All of these events could initiate a fibrogenic and/or tumorigenic
response in the spleen. The spleen toxicity of aniline is studied more and the different mechanisms
are suggested. This review summarizes those events following aniline exposure that induce spleen
toxicity and neurotoxicity.
