title: Protective effects of exogenous β-hydroxybutyrate on paraquat toxicity in rat kidney.
abstract: In this study, we demonstrated the protective effects of β-hydroxybutyrate (β-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, β-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). β-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 Bcl-2 and Bax, which were also effectively blocked by β-HB. Moreover, treatment of PQ strongly decreased the nuclear Nrf2 levels. However, pre-treatment with β-HB effectively suppressed this action of PQ. This may imply the important role of β-HB on Nrf2 pathway. Taken together, this study provides a novel finding that β-HB has a renoprotective ability against paraquat-induced kidney injury.
authors.affiliation: College of Veterinary Medicine, Jilin University, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wei
authors.affiliation: College of Veterinary Medicine, Jilin University, China.
authors.forename: Wulin
authors.initials: W
authors.lastname: Tian
authors.affiliation: College of Veterinary Medicine, Jilin University, China.
authors.forename: Fangning
authors.initials: F
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Jilin University, China. Electronic address: xiegh@jlu.edu.cn.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Xie
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006540:Herbicides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D006540:Herbicides; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D003404:Creatinine; D002374:Catalase; D013482:Superoxide Dismutase; D011065:Poly(ADP-ribose) Polymerases; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D005978:Glutathione; D010269:Paraquat; D020155:3-Hydroxybutyric Acid
keywords: Apoptosis; Kidney injury; Oxidative stress; Paraquat; β-Hydroxybutyrate