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.