title: Melatonin modulates endoplasmic reticulum stress and Akt/GSK3-beta signaling pathway in a rat model of renal warm ischemia reperfusion.
abstract: Melatonin (Mel) is widely used to attenuate ischemia/reperfusion (I/R) injury in several organs. Nevertheless, the underlying mechanisms remain unclear. This study was conducted to explore the effect of Mel on endoplasmic reticulum (ER) stress, Akt and MAPK cascades after renal warm I/R. Eighteen Wistar rats were randomized into three groups: Sham, I/R, and Mel + I/R. The ischemia period was 60 min followed by 120 min of reperfusion. Mel (10 mg/kg) was administrated 30 min prior to ischemia. The creatinine clearance, MDA, LDH levels, and histopathological changes were evaluated. In addition, Western blot was performed to study ER stress and its downstream apoptosis as well as phosphorylation of Akt, GSK-3β, VDAC, ERK, and P38. Mel decreased cytolysis and lipid peroxidation and improved renal function and morphology compared to I/R group. Parallely, it significantly reduced the ER stress parameters including GRP 78, p-PERK, XBP 1, ATF 6, CHOP, and JNK. Simultaneously, p-Akt level was significantly enhanced and its target molecules GSK-3β and VDAC were inhibited. Furthermore, the ERK and P38 phosphorylation were evidently augmented after Mel administration in comparison to I/R group. In conclusion, Mel improves the recovery of renal function by decreasing ER stress and stimulating Akt pathway after renal I/R injury.
authors.affiliation: Unit of Molecular Biology and Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, rue Avicenne, 5000 Monastir, Tunisia.
authors.forename: Kaouther
authors.initials: K
authors.lastname: Hadj Ayed Tka
authors.affiliation: Unit of Molecular Biology and Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, rue Avicenne, 5000 Monastir, Tunisia.
authors.forename: Asma
authors.initials: A
authors.lastname: Mahfoudh Boussaid
authors.affiliation: Unit of Molecular Biology and Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, rue Avicenne, 5000 Monastir, Tunisia.
authors.forename: Mohamed Amine
authors.initials: MA
authors.lastname: Zaouali
authors.affiliation: Laboratory of Histology and Embryology, Faculty of Dental Medicine, University of Monastir, rue Avicenne, 5000 Monastir, Tunisia.
authors.forename: Rym
authors.initials: R
authors.lastname: Kammoun
authors.affiliation: Unit of Experimental Hepatic Ischemia-Reperfusion, Institute of Biomedical Investigations, Higher Council of Scientific Investigations, 08036 Barcelona, Spain.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bejaoui
authors.affiliation: Laboratory of Histology and Embryology, Faculty of Dental Medicine, University of Monastir, rue Avicenne, 5000 Monastir, Tunisia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ghoul Mazgar
authors.affiliation: Unit of Experimental Hepatic Ischemia-Reperfusion, Institute of Biomedical Investigations, Higher Council of Scientific Investigations, 08036 Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Rosello Catafau
authors.affiliation: Unit of Molecular Biology and Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, rue Avicenne, 5000 Monastir, Tunisia.
authors.forename: Hassen
authors.initials: H
authors.lastname: Ben Abdennebi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003404:Creatinine / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008550:Melatonin / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D052096:Warm Ischemia; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D008315:Malondialdehyde; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D008550:Melatonin