title: Nephroprotective effect of GSK-3β inhibition by lithium ions and δ-opioid receptor agonist dalargin on gentamicin-induced nephrotoxicity.
abstract: Nephrotoxicity and ototoxicity are the most considerable side effects of aminoglycoside antibiotics, such as gentamicin that seriously limits its application in medicine. The major mechanism of negative effect of gentamicin on kidney cells involves damage of mitochondria and induction of an oxidative stress that causes cell death resulting in kidney dysfunction. In this work we compared effects of the lithium ions and δ-opioid receptors agonist, dalargin on gentamicin-induced kidney injury. It was revealed that LiCl and dalargin treatment reduced renal tubular cell death and diminished kidney injury caused by gentamicin. Both LiCl and dalargin were found to enhance phosphorylation of glycogen synthase kinase 3β in the kidney which points to induction of nephroprotective signaling pathways. Thus, we conclude that lithium ions and dalargin might be considered as novel promising agents for future use to prevent negative consequences of therapy with aminoglycoside antibiotics.
authors: Lomonosov Moscow State University, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow 119992, Russia. plotnikov@genebee.msu.ru
authors: E Y
authors: EY
authors: Plotnikov
authors: O A
authors: OA
authors: Grebenchikov
authors: V A
authors: VA
authors: Babenko
authors: I B
authors: IB
authors: Pevzner
authors: L D
authors: LD
authors: Zorova
authors: V V
authors: VV
authors: Likhvantsev
authors: D B
authors: DB
authors: Zorov
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control*; D000818:Animals; D015153:Blotting, Western; D002414:Cations, Monovalent / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects; D016308:Enkephalin, Leucine-2-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005839:Gentamicins / Q000633:toxicity*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006651:Histocytochemistry; D018020:Lithium Compounds / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists
chemical_list: D002414:Cations, Monovalent; D005839:Gentamicins; D018020:Lithium Compounds; D017465:Receptors, Opioid, delta; D016308:Enkephalin, Leucine-2-Alanine; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; C040996:enkephalin-Leu, Ala(2)-Arg(6)-