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. 2022 Jan 13;12:791036. doi: 10.3389/fphys.2021.791036

Table 5.

The proposed molecular and cellular mechanism of the protective effect of melatonin for renal I/R injury.

References Mechanism Effect
Sener et al. (2002) Oxidative stress Decreased MDA, MPO and PO, increased GSH
Kunduzova et al. (2003) Oxidative stress, and apoptosis Decreased MDA, and blocked caspase−3 activity
Sahna et al. (2003) Oxidative stress Decreased MDA
Rodríguez-Reynoso et al. (2004) Oxidative stress, and inflammation Decreased MDA, MPO, and iNOS, increased GSH, and blocked neutrophil infiltration
Aktoz et al. (2007) Oxidative stress, cast formation, and tubular necrosis Decreased MDA, increased SOD, and CAT
Kurcer et al. (2007a) Oxidative stress Decreased MDA, PC, and NO
Kurcer et al. (2007b) Inflammation Decreased TNF-α, IL-β, and IL-6
Fadillioglu et al. (2008) Oxidative stress Decreased MDA, MPO, TAC, and TOS
Ersoz et al. (2009) Oxidative and nitrosative stress Decreased MDA, PCC, NOx, SOD, and GSH-Px
Sinanoglu et al. (2012) Apoptosis Blocked caspase-3 activity
Ahmadiasl et al. (2013) Oxidative stress, and inflammation Decreased MDA, increased SOD, CAT, and GSH-Px, inhibit mononuclear cell infiltration
Sezgin et al. (2013) Oxidative stress Decreased MDA and NO, increased SOD, and GSH
Ahmadiasl et al. (2014a) Oxidative stress Decreased MDA, increased TAC, SOD, and GSH-Px
Ahmadiasl et al. (2014b) Oxidative stress, and apoptosis Decreased MDA and TNF-α, increased TAC, and bcl2
Cetin et al. (2014) Oxidative stress Decreased MDA and XO, increased GSH-Px
Sehajpal et al. (2014) Oxidative stress Decreased MDA, TBARS and SAG, increased CAT and GSH
Hadj Ayed Tka et al. (2015) Oxidative stress, ER stress, and apoptosis Decreased MDA, inhibited ER stress (phosphorylation of GRP 78, p-PERK, ATF 6, CHOP and JNK), and phosphorylation of Akt, GSK-3, VDAC, ERK, and P38
Oguz et al. (2015) Inflammation Decreased TNF-α and IL-6
Yilmaz et al. (2015) Oxidative stress Decreased MDA, increased GSH
Yip et al. (2015) Glomerular integrity, Oxidative stress, and Inflammation Enhanced glomerular integrity (ZO-1, p-cadherin, podocin, dystroglycan, fibronectin), inhibited protein expressions of inflammatory (TNF-α/NF-κB/MMP-9) and oxidative stress (NOX-1, NOX-2, oxidized protein)
Banaei et al. (2016a) Oxidative stress Decreased MDA, SOD, and GSH-Px
Banaei et al. (2016b) Morphological damage Increase the observed Hb and Hct values, decreased the hyaline cast and thickening of the Bowman capsule basement membrane
Chang et al. (2016) Inflammation, apoptotic Inhibited inflammatory (TLR 4, iNOS, and IL-1β), apoptotic (mitochondrial Bax, cleaved caspase-3 and p53), podocyte dysfunction (Wnt1/Wnt4/β-catenin), and enhanced podocyte integrity (E/P-cadherin), and cell survival (PI3K/AKT/mTOR)
Shi et al. (2019) Oxidative stress, and apoptosis Decreased MDA, increased SOD, inhibited SIRT1 expression, and Nrf2/HO-1 signaling
Souza et al. (2018) Oxidative stress Increased SOD and CAT
Chen et al. (2019a) Apoptosis, and renal fibrosis Inhibited the interaction of TGF-β/Smad and Wnt/β-catenin
Chen et al. (2019b) Oxidative stress and inflammation, fibrosis and podocyte injury Upregulated Gas6/Axl/NF-κB/Nrf2 signaling to reduce oxidative stress and inflammation in AKI and downregulated Gas6/Axl signaling
M El Agaty and Ibrahim Ahmed (2020) Oxidative stress Decreased pancreatic MDA and TNF-α
Wang et al. (2020) Cytoplasmic calcium overload, myocardial damage, mitochondrial calcium accumulation Induced phosphorylation of the IP3R/MCU pathways
Yang et al. (2020) Oxidative stress, apoptotic, inflammation, autophagy Decreased MDA, TNF-α, IL-2, IL-6, and IL-10 increased SOD, GSH and CAT, inhibited MyD88-dependent TLR4 and MEK/ERK/mTORC1 signaling
Zahran et al. (2020) Oxidative stress, apoptotic, inflammation Decreased MDA, IL-1β, kidney injury molecule-1, IL-18, MMP9, TNF-α and NF-κB, increased SOD and CAT, reduced apoptosis (lower DNA damage and bax, and higher bcl-2)

MDA, malondialdehyde; MPO, myeloperoxidase; PO, protein oxidation; GSH, glutathione; iNOS, inducible nitric oxide synthase; SOD, superoxide dismutase; CAT, catalase; PC, protein carbonyl; NO, nitric oxide; TNF-α, tumor necrosis factor-α; Interleukin-1β, IL-1β; Interleukin-6, IL-6; TAC, total antioxidant capacity; TOS, total oxidative stress; bcl-2, B-cell lymphoma-2; XO, xanthine oxidase; TBARS, thiobarbituric acid reactive substances; SAG, superoxide anion generation; glucose regulated protein 78, GRP 78; p-PERK, phospho-protein kinase R-like endoplasmic reticulum kinase; XBP 1, X-box binding protein 1; ATF-6, activating transcription factor-6; CHOP, C/EBP homoiogousprotein; JNK, c-Jun N-terminal kinase; GSK-3, glycogen synthase kinase 3; VDAC, voltage-dependent anion channels; ERK, extracellular regulated protein kinases; ZO-1, zonula occludens-1; NF-κB, nuclear factor-kappa B; MMP-9, matrix metalloproteinase 9; NOX, nicotinamide adenine dinucleotide phosphate oxidase; Hb, hcthemoglobin; Hct, hematocrit; TLR 4, Toll-like receptor; Nrf2, nuclear factor E2-related factor 2; HO-1, heme oxygenase-1; Inositol 1,4,5-trisphosphate receptor type I, IP3R; MCU, mitochondrial Ca2+ uniporter; TGF-β, transforming growth factor-β; growth arrest specific 6, GAS6; MyD88, myeloid differentiation factor 88.