<Background and aims> High mobility group box 1 (HMGB1), a nuclear protein, is released from various cells including macrophages (Mφs), and aggravates inflammation. We have shown a crucial role of HMGB1 in chemotherapy-induced peripheral neuropathy (CIPN). On the other hand, HMGB1 released from hepatic cells and causes hepatic disorder. To clarify the risk of hepatic disorder for CIPN, we investigated the aggravation of oxaliplatin (OHP)-induced peripheral neuropathy in mice with hepatic injury induced by CCl4 or ethanol. <Methods> Mice received i.p. OHP at 1-5 mg/kg, and mechanical allodynia was evaluated by von Frey test. Serum AST, ALT and HMGB1 was determined using an automatic analyzer with its exclusive colorimetric assay kit or ELISA kit. <Results> In mice, i.p. OHP at 5 mg/kg, but not 1 mg/kg, caused mechanical allodynia, which was prevented by an anti-HMGB1 antibody or soluble thrombomodulin (TM) capable of inactivating HMGB1. CCl4 (1%, 5 ml/kg, i.p.) or ethanol (25%, 20 ml/kg x 3 for 2 days, p.o.) significantly increased AST and ALT levels and tended to elevate HMGB1 levels in serum. CCl4 (every 2 days, 3 times) or ethanol (twice a day, 12 times) did not alter nociceptive threshold in naïve mice, but caused remarkable allodynia in the mice treated with OHP at 1 mg/kg, a subeffective dose, which was blocked by anti-HMGB1 antibody or TM. <Conclusions> Thus, hepatic disorder is considered a risk factor for aggravation of OHP-induced CIPN in mice, where HMGB1 might play a key role.

HEPATIC INJURY AGGRAVATES OXALIPLATIN-INDUCED PERIPHERAL NEUROPATHY IN MICE: POSSIBLE INVOLVEMENT OF HMGB1