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Although the direct cytotoxic effects of high cellular GSSG levels have been documented in a variety of cell types 33,34,35,36 , our cell culture studies with hepatocytes revealed that increased GSSG accumulation, despite being non-toxic per se, could sensitize hepatocytes to TNF-induced killing, suggesting that GSSG and TNF can synergistically induce hepatocyte death and that GSSG-triggered sensitization to TNF hepatotoxicity represents a clinically relevant process that may account for disease progression in NAFLD

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Several previous studies have concluded that aberrant, non-native disulfide bonds involving Cys-6 and Cys-111 result in inclusion formation and disulfide reduction (Deng et al., 2006