Protective effect of agmatine against cisplatin-induced apoptosis in an auditory cell line

Abstract

23Objectives: Agmatine, an endogenous metabolite of arginine, is known to have 24 antioxidant activity, protect mitochondrial function, and confer resistance to cellular 25 apoptosis. The aim of this study was to evaluate the protective effects of agmatine 26 against cisplatin-induced cellular apoptosis in an auditory cell line. 27 Methods: HEI-OC1 cells were co-treated with agmatine at different concentrations and 28 15 µM cisplatin for 48 h. Cell viability was measured and annexin V-FITC/propidium 29 iodide (PI) staining was performed to analyze apoptosis. The levels of intracellular 30 reactive oxygen species (ROS) were measured using flow cytometry. The expression 31 of BAX (Bcl2-associated X protein) and the enzymatic activity of caspase-3 were 32 measured to examine the pathway of apoptosis induction. 33 Results: Co-treatment with 8 mM agmatine protected HEI-OC1 cells against cisplatin-34 induced cell apoptosis. Agmatine exerted a significant protective effect against 15 µM 35 cisplatin when applied for 48 h and reduced the proportion of necrotic and late 36 apoptotic cells. Agmatine did not reduce the cisplatin-induced increase in ROS but 37 decreased the expression of BAX and the activity of caspase-3. 38 Conclusions: Agmatine protected against cisplatin-induced cellular apoptosis in an 39 auditory cell line. These effects were mediated by the protection of mitochondrial 40 function and inhibition of apoptosis. 128 ChemiDOC touch imaging system (Bio-Rad, Hercules, CA). The relative band 129 densities were computed using ImageJ software (Imagej.nih.gov/ij/index.html).

Agmatine Alleviates Cisplatin-Induced Ototoxicity by Activating PI3K/AKT Signaling Pathway

“…It is worth noting that agmatine has anti-inflammatory effects, effectively inhibiting the transcription factor NF-κB ( Li et al, 2020 ). As to the safe dose identified in our study (200 μ m agmatine), a preprint paper indicates that the safe dose of agmatine can reach to 10 m m ( Park et al, 2020 ). Such discrepancy may need further detailed analysis.…”