Review on Molecular Mechanism of Aniline Induced Spleen Toxicity: Rat Exposure

Aniline exposure leads to selective toxicity to the spleen and makes diverse sarcoma which is characterized by hyperplasia, splenomegaly, and fibrosis and tumour formation at the end. However, the precise molecular mechanism(s) of aniline-induced spleen toxicity is not well understood, previous studies have represented that the Aniline exposure result in iron overload which initiate oxidative/nitrosative disorder stress in the spleen and oxidative damage to proteins, lipids and DNA as a result. Aniline exposure can also increase cell proliferation. Critical factors in cell cycle regulation such as cyclins, cyclin-dependent kinases (CDKs), pRB protein, and cell cycle regulatory proteins (cyclins A, B and CDK1) and CDK inhibitors (p21 and p27) could be changed in aniline-induced tumorigenic response in the spleen. Oxidative DNA damage and induction of DNA glycosylases expression (OGG1, NEIL1/2, NTH1, APE1 and PNK) for removal of oxidative DNA lesions are also associated with this toxicity. Activation of redox-sensitive transcription factors, nuclear factor-kappa B and AP-1, as a result of oxidative stress, leads to up-regulation of fibrogenic/inflammatory cytokines (IL-1, IL-6 and TNF-α) transcription in aniline treated-rats. Phosphorylation of IκB kinases (IKKα and IKKβ) along with upstream signaling events, as mitogen-activated protein kinases (MAPKs), is potentially considered as an initiator of NF-κB and AP-1 activation. Although different effects of aniline in spleen toxicity are studied and different mechanisms are suggested, this review summarizes those events following oxidative stress, as a major mechanism of toxicity, which finally initiate a fibrogenic and/or tumorigenic response in rat.

کلیدواژه ها:

Aniline ، Spleen toxicity ، Oxidative stress ، Cyclin ، Cytokine ، Transcription factor