Objective: The glycopeptide antibiotic colistin (polymyxin E) causes dose-dependent nephrotoxicity. The pathophysiology of colistin-induced nephrotoxicity involves processes such as ischemia, inflammation, and apoptosis. By alleviating oxidative stress, inflammation, and apoptosis, crocin, a key component of Crocus sativus protects the kidneys from toxicity.  This study designed to explore the protective effects of crocin against colistin-induced cytotoxicity in HEK-293 cells.
Materials and Methods: HEK-293 cells were treated with varying concentrations of crocin (1.25 - 40 μM) for 24 hr before exposure to 160 µM colistin (the IC50 value). Cell viability was measured using an MTT assay. Intracellular reactive oxygen species (ROS) levels were measured using DCFH, and Western blotting was performed to analyze the expression of Bcl-2, Bax, and caspase-3 proteins.
Results: Pre-treatment with crocin at concentrations of 1.25 (p<0.001), 2.5, and 5 (p<0.01) µM effectively enhanced cell viability, which had been diminished by colistin. Furthermore, crocin mitigated the elevated levels of ROS induced by colistin (p<0.001). The findings reveal that crocin prevented the upregulation of pro-apoptotic proteins Bax (p<0.05) and caspase-3 (p<0.01), and countered the downregulation of the anti-apoptotic protein Bcl-2 (p<0.05) triggered by colistin in HEK-293 cells.
Conclusion: Crocin serves as a natural compound that alleviates colistin-induced cytotoxicity through inhibiting oxidative stress and preventing apoptosis induction. As a result, crocin stands out as a promising antioxidant for preventing colistin-induced cytotoxicity, especially in renal cells.