Alpha lipoic acid attenuates iron induced oxidative acute kidney injury in rats


ÇAVDAR Z., Oktan M. A. , Ural C., Kocak A., Calisir M. , Heybeli C., ...More

BIOTECHNIC & HISTOCHEMISTRY, vol.96, no.6, pp.409-417, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 96 Issue: 6
  • Publication Date: 2021
  • Doi Number: 10.1080/10520295.2020.1812001
  • Title of Journal : BIOTECHNIC & HISTOCHEMISTRY
  • Page Numbers: pp.409-417
  • Keywords: Alpha lipoic acid, iron, kidney injury, NOX4, PI3K, Akt, p38 MAPK, rat, TRACE-ELEMENTS, RENAL-FAILURE, STRESS, ACTIVATION, CELL, INHIBITION, APOPTOSIS, TISSUE

Abstract

Iron has been implicated in oxidative tissue injury owing to its ability to generate reactive oxygen species (ROS). We investigated the reno-protective effects of alpha lipoic acid (ALA) by investigating its effects on the kidney isoform of NADPH oxidase (Nox4) and the specific signaling pathways, p38 MAPK and PI3K/Akt, which participate in apoptosis and survival, respectively. We established four groups of seven rats: control, 100 mg/kg ALA, 80 mg/kg iron sucrose (IS) and IS + ALA. IS and ALA were injected intravenously and rats were sacrificied after 6 h. The mRNA expression of the subunits of NADPH oxidase, Nox4 and p22phox; tumor necrosis factor-alpha (TNF-alpha); and kidney injury molecule-1 (KIM-1) were measured using quantitative real time polymerase chain reaction (qRT-PCR). Active caspase-3 protein expression was evaluated by immunostaining. Also, p38 MAPK and PI3K/Akt signaling pathways were analyzed using western blot. ALA suppressed the mRNA expression of Nox4, p22phox, TNF-alpha and KIM-1. Active caspase-3 protein expression induced by IS was decreased by ALA. ALA also suppressed p38 MAPK and activated the PI3K/Akt signaling pathway following IS administration. We found that ALA may be an effective strategy for preventing oxidative acute kidney injury caused by IS.