Fig. 2

Chemoprotective effects of apigenin. Part. 1, a mouse was administrated with cisplatin. In order to investigate the molecular mechanisms of renal injury by cisplatin, followed by treatment, kidney cells were extracted and molecular analysis were performed. Cisplatin causes nephrotoxicity by oxidative stress, inflammation, apoptosis, and necrosis. Cisplatin enters into the renal cells by OCT-2 and over-activates CYP2E1 as an active producer of ROS in mitochondria and triggers ROS production which in turn leads to oxidative stress, lipid peroxidation, different cytokines (IL-6 and IL-1β) production, MAPK pathway activation and cell death. CYP2E1 plays a pivotal role in the promotion of oxidative stress in the kidney and increases cisplatin-induced nephrotoxicity. The produced ROSs by CYP2E1 can activate NF-κB and MAPK. NF-κB is a pro-inflammatory transcription factor and regulates the expression of different inflammatory factors. NF-κB is separated in the cell cytosol by binding to an inhibitory protein, IκB. Whenever, NF-κB is stimulated by stimuli such as viral, bacterial or other pathogens, a proteasome ubiquitinates and degrades IκB and releases NF-κB to translocate to the nucleus. In the nucleus it triggers the expression of target genes, like TNF-α, IL-1β and TGFβ which play important roles in cisplatin-induced kidney injury. Part 2, a pre-treated mouse by apigenin, was treated with cisplatin. The molecular analysis of the renal cells demonstrates that pre-treatment by apigenin significantly reduced cisplatin-induced renal injury by anti-oxidant and anti-inflammatory effects. Apigenin significantly suppressed the cisplatin-induced increase in the CYP2E1 levels in the mouse. Subsequently, it inhibited the renal oxidative stress, lipid peroxidation, generation of pro-inflammatory cytokines like TNF-α, IL-1β and TGFβ from the kidney tissue of cisplatin-treated mouse. Apigenin protected kidney cells against DNA damage (apoptosis) after cisplatin administration. It also significantly decreased the activities of NF-κB p65 and p38MAPK that were increased by cisplatin. (Inhibition  Activation)