Allethrin toxicity on human corneal epithelial cells involves mitochondrial pathway mediated apoptosis

• Allethrin induces apoptosis in human corneal epithelial cells through intrinsic pathway.
• Allethrin alters Bax and Bcl-2 ratio and induces release of cytochrome c.
• Increase of cells in sub G0–G1 phase of cell cycle was observed with allethrin treatment.
• Allethrin treatment induces the expression levels of TNF-α, IL-1β and MMP-9.

Pyrethroids including allethrin are the most common commercial household insecticides. The detrimental effects caused by pyrethroids on humans are gaining considerable attention. The present study was aimed to elucidate the effects of allethrin on the human corneal epithelial (HCE) cells. Allethrin inhibited the proliferation of HCE cells in a dose-dependent manner. In the presence of allethrin, cells showed membrane blebbing and nuclear fragmentation along with significant decrease in mitochondrial membrane potential resulting in increased cytochrome c (Cyt c) release into the cytosol. Further, flow cytometry analysis demonstrated a marked increase in sub G0–G1 cells, characteristic of apoptosis. Increased expression of pro-apoptotic protein, Bax, a simultaneous decrease of anti-apoptotic protein, Bcl-2, and activation of Caspase 3 was evident in the treated cells. In addition, extracellular matrix digesting metalloproteinase 9 (MMP-9) was also stimulated. Furthermore, significant increase in the gene expression of inflammatory cytokines, TNF-α and IL-1β was observed. Taken together, these findings suggest that allethrin (IC50 ≈ 85 μM) is toxic to HCE cells causing death through mitochondrial pathway.