In this study, we demonstrated the protective effects of beta-hydroxybutyrate (beta-HB) against paraquat (PQ)-induced kidney injury and elucidated the underlying molecular mechanisms. By histological examination and renal dysfunction specific markers (serum BUN and creatinine) assay, beta-HB could protect the PQ-induced kidney injury in rat. PQ-induced kidney injury is associated with oxidative stress, which was measured by increased lipid peroxidation (MDA) and decreased intracellular anti-oxidative abilities (SOD, CAT and GSH). beta-HB pretreatment significantly attenuated that. Caspase-mediated apoptosis pathway contributed importantly to PQ toxicity, as revealed by the activation of caspase-9/-3, cleavage of PARP, and regulation of Bc1-2 and Bax, which were also effectively blocked by beta-HB. Moreover, treatment of PQ strongly decreased the nuclear Nrf2 levels. However, pre-treatment with beta-HB effectively suppressed this action of PQ. This may imply the important role of beta-HB on Nrf2 pathway. Taken together, this study provides a novel finding that beta-HB has a renoprotective ability against paraquat-induced kidney injury. (c) 2014 Elsevier Inc. All rights reserved.