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Introduction
Aristolochic acid (AA) is a component present in Chinese herbs (for example Asarum and Aristolochia) from remedies for the treatment of arthritis pain, coughs and gastrointestinal symptoms (1–4). Previous studies have indicated that AA can lead to renal injury (5,6) and this finding has led to further studies (7,8). Previous studies have indicated that renal damage from renal cell death and renal fibrosis is associated with AA treatment (9,10).
AA-induced oxidative stress may serve an important role in the development of renal injury (11–13). Previous studies have demonstrated that oxidative stress causes lipid peroxidation, DNA damage and protein peroxidation, and results in cell damage (14–16). O2− and H2O2 are key reactive oxygen species (ROS) identified in cells (17,18). Normally, O2− and H2O2 are produced in the mitochondria via electron transport chain (19,20) and these ROS are removed by cellular superoxide dismutase (SOD), glutathione peroxidase (Gpx) and catalase (CAT) (21–23). However, various toxins also induce O2− and H2O2 production (24–26). The excessive O2− and H2O2 lead to cell injury (27,28) and it has additionally been reported that AA-induced H2O2 leads to renal damage (29).
Various studies have demonstrated that oxidative stress can induce cell apoptosis or cell necrosis (30–32), and consequently AA-induced oxidative stress can cause apoptosis or necrosis of renal cells (29,33–35). Concerning apoptosis, caspase-dependent and caspase-independent pathways have been reported previously (36,37). Although certain mechanisms of AA-induced cell death remain unclear, the caspase activation may be associated with AA-induced apoptosis (38,39). Previous studies indicated that AA can activate caspase-9 and caspase-3 leading to cell apoptosis (40–42).
The isoforms of vitamin E consist of α-tocopherol, β-tocopherol, δ-tocotrienol and γ-tocotrienol (43). Among them, α-tocopherol possesses anti-oxidative activities and has been used in a clinical setting (44,45). In addition, previous studies have suggested that α-tocopherol can inhibit renal fibrosis (46,47). Due to the fact that AA-induced renal injury was associated with oxidative damage and fibrotic renal injury (9,11–13), the effects of α-tocopherol on AA-induced renal cell cytotoxicity were studied. The results of the present study demonstrated that α-tocopherol can inhibit the H2O2 level and caspase-3 activities to attenuate...