In-vitro alleviation of ochratoxin a mediated cytotoxicity using N-acetyl-L-tryptophan glucoside pretreatment

Abstract

AimsOchratoxin A (OTA) has been reported to exhibit nephrotoxicity through induction of cell redox homeostasis perturbation, mitochondrial hyperpolarization and depolarization, protein synthesis inhibition, apoptosis, etc. In the present examination, the protective efficiency of novel synthesized molecule, N-acetyl-L-Tryptophan glucoside (NATG) towards OTA prompted toxicity was evaluated using Human Embryonic Kidney (HEK-293) cells. Main methods & key findingsThe cells were treated with NATG (0–200 μg/ml) before OTA treatment (0-20 μg/ml) the and protection efficiency of NATG was evaluated using MTT and SRB assay. OTA-induced intracellular ROS and its inhibition via NATG (10 μg/ml) pre-treatment was evaluated using the 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) probe. Protective effects of NATG pre-treatment on OTA treated cells had been evaluated in terms of oxidative stress, cell cycle perturbations, mitochondrial membrane disturbance and apoptotic modulation through flowcytometry. Results of the study demonstrated that NATG provides significant protection to HEK -293 cells against OTA induced toxicity primarily by reducing oxidative stress, maintaining mitochondrial membrane homeostasis and inhibiting apoptosis. Furthermore, molecular docking study demonstrated that NATG may efficiently bind with OTA binding pocket on phenylalanyl t-RNA synthetase, resulting in inhibiting OTA incorporation within the newly synthesized peptides and therefore may ameliorate OTA mediated protein synthesis inhibition. SignificancePresent study demonstrated a significant protective efficacy of N acetyl-L- tryptophan glucoside (NATG) against OTA induced toxicity in HEK -293 cells. In future, NATG can be developed as a potential protective agent against OTA induced toxicity in humans.