Ellagic Acid from Terminalia arjuna Fruits Protects Against Chromium and Cobalt Toxicity in Primary Human Lymphocytes

Increased accumulation of heavy metal ions such as Cr⁶⁺ and Co²⁺ due to release from prostheses and metallic implants has been reported. These metal ions have been shown to affect both resting and activated lymphocytes. Natural remedies towards mitigating the cytotoxic effects of metal ions are clearly warranted. Polyphenolic compounds which are part of hydrolysable tannins from natural plant sources are considered effective in cheating heavy metal ions in a biological system. We have isolated and characterized a polyphenolic compound (ellagic acid) from Terminalia arjuna fruits that has been tested for its ability to attenuate the metal ion toxicity in primary human lymphocytes in culture. Cr⁶⁺ and Co²⁺ (100 μM) decreased lymphocyte viability and proliferation and increased apoptosis of resting as well as CD3 and/or CD28-stimulated lymphocytes. Metal ions markedly diminished the cytokine (interleukin-2 and interferon-γ) secretion from activated lymphocytes. Pretreatment with ellagic acid at 25, 50, and 100 μM concentrations effectively improved viability and proliferative responses of both resting and activated lymphocytes, while attenuating the apoptotic index. Ellagic acid also tended to normalize the cytokine secretion from the activated lymphocytes even in the presence of metal ions, suggesting broad effects on the adaptive immune system.