Allicin based inhibition of eryptosis: A novel therapeutic approach against hyperosmolarity triggered anemia

Background: Hyperosmotic stress is often overlooked in various clinical conditions like diabetes and may lead to anemia. Erythrocytes are very sensitive cells in body circulation and are affected by very minute changes in the environment. Eryptosis (suicidal death of erythrocytes) is mainly characterized by phosphatidylserine exposure, cell shrinkage, blabbing and is triggered by hyperosmolarity, oxidative stress, energy depletion, xenobiotic exposure and activation of various kinases. Objective: This study was planned to evaluate the eryptotic effects of hyperosmolarity by stimulating p38 MAPK and enhanced ROS generation and allicin’s anti-hemolytic, antioxidant, p38MAPK inhibitory and anti-eryptotic potential. Methods: Effects of allicin on erythrocytes facing hyperosmolarity were confirmed by measuring enzyme activity (SOD, GPx and CAT), ROS level, eryptotic marker (change in cell size and phosphatidylserine exposure) and underlying mechanisms of eryptosis (role of Ca2+ in eryptosis and p38 MAPK activation) were confirmed. To measure the cytotoxic effects of allicin hemolysis % was measured. To check statistical significance of data ANOVA was used. Results: Results confirmed that allicin treatment enhances SOD, GPx and CAT activity, reduces ROS level, p38 MAPK activation and Ca2+ effects, positively affects cell size (normal range) and phosphatidylserine exposure (reduced) and reduces hemolysis % in erythrocytes facing hyperosmolarity. Conclusion: It is concluded from this study that hyperosmolarity is the main stimulator of eryptosis and leads to anemia in various clinical conditions, while allicin treatment helps to increase erythrocyte survival by inhibiting and attenuating various pathways and reducing eryptpotic rate. Allicin’s anti-eryptotic and cytoprotective potential gives foundation for future clinical research targeting hyperosmolarity triggered anemia.