Table 2.
Characteristics of included animal models/studies.
| Author and Year | Kim et al. (2014) | Xiong et al. (2015) | Kim et al. (2016) | Xue et al. (2016) | Lin et al. (2017) | Hao et al. (2019) | Xiong et al. (2019) |
|---|---|---|---|---|---|---|---|
| Animal (species) | -C57BL/6 mouse -NQO1 knockout mice on C57BL/6 background | C57BL/6 mouse | -C57BL/6 mouse -NQO1 knockout mice on C57BL/6 background | C57BL/6 mouse | db mice | C57BL/6 mouse | -C57BL/6 mice -miR-34a +/– mice and SIRT1 transgenic mice on C57BL/6 background |
| Type of SNHL investigated | Ototoxic drug-induced | ARHL | Ototoxic drug-induced | ARHL | Diabetes-related hearing loss | ARHL | ARHL |
| Study design—Experimental | |||||||
| Treatment group(s) | -Cisplatin-β-Lap + cisplatin-β-Lap alone | -Old-15 additional mice (2–3 months) for resveratrol treatment group (400 mg/kg/day for a period of 2 months) | -Cisplatin-Dunnione + cisplatin-Dunnione alone | Old | db/db mice (BKS.Cg-m+/+ Leprdb/J) | Old | -Old-Old + 3 treatment groups (at the age of 2 months, mice were started supplementary diet for 10 months with -high dose resveratrol (300 mg/kg/day) -low dose resveratrol (7.5 mg/kg/day) -rapamycinm (14 mg/kg/day) |
| Sample size | 5 each | 50 | 5 each | 30 | 21 | No data | varied |
| Age | 8 weeks | 12–16 months | 8 weeks | 12 months | 8 weeks | 12–16 months | 12 months |
| Control group(s) | No treatment/s | -Young -13 additional mice (2–3 months) for resveratrol control group (standard chow) | No treatment/s | Young | db/m (C57BL/KSJ db/+) | Young | Young |
| Sample size | 5 | 47 | 5 | 30 | 21 | No data | varied |
| Age | 8 weeks | 1–2 months | 8 weeks | 1–2 months | 8 weeks | 1–2 months | 2 months |
| Induction of hypoxia/oxidative stress/ischemia | |||||||
| Method of induction | Chemical | Ageing | Chemical | Ageing | No data | Ageing | Ageing |
| Reagents used | Cisplatin | Cisplatin | |||||
| Dosage | 16 mg/Kg | 20 mg/Kg | |||||
| Exposure time | single intraperitoneal dose | single intraperitoneal dose | |||||
| Post-treatment interval | 4 days | 4 days | |||||
| Techniques used to confirm hypoxia-induction/ROS production | -H2-DCFDA Florescent Assay Kit -Chemiluminescent, PARP Assay Kit -Fluorescent SIRT1 Assay Kit -Fluorescent NAD+/NADH Detection Kit -Western blotting and densitometry (H2AX)-TUNEL Assay Kit | TUNEL Assay Kit | -H2-DCFDA Florescent Assay Kit -Chemiluminescent, PARP Assay Kit -Fluorescent SIRT1 Assay Kit -Western blotting and densitometry (H2AX) | -TUNEL Assay Kit-JC-1 Fluorescence Kit | TUNEL Assay Kit | -JC-1 Fluorescence Kit -TUNEL Assay Kit | -Immunocyto-chemistry -Western blotting and densitometry |
| MicroRNA investigations | |||||||
| Samples used to extract RNAs | cochlea | cochlea | cochlea | cochlea | cochlea | cochlea | cochlea |
| Technique used to determine the gene expression | qRT-PCR | qRT-PCR | qRT-PCR | qRT-PCR | qRT-PCR | qRT-PCR | qRT-PCR |
| Reported differentially expressed miRNAs / candidate miRNAs | miR-34a | miR-34a | miR-34a | miR-29b | miR-34a | miR-29b | miR-34a |
| Target gene expressions | |||||||
| Technique used to determine the gene expression | No data | qRT-PCR | qRT-PCR | qRT-PCR | qRT-PCR | qRT-PCR | No data |
| and Validation methods | -Western blotting and densitometry-Immunohisto-chemistry | -Immunohisto-chemistry, -Western blotting and densitometry | -Western blotting and densitometry-Immunohisto-chemistry | Western blotting and densitometry | Western blotting and densitometry | Western blot | -Immunocyto-chemistry, -Western blotting and densitometry, -Genotyping |
| Reported predicted and/or validated gene(s) | SIRT1, PARP-1, p53, NF-kB p65 | SIRT1, p53, acetyl p53 | SIRT1, PARP-1, p53, NF-kB p65, TNF-α | SIRT1, PGC-1α | SIRT1, HIF-1α | MIAT, SIRT1, PGC-1α | SIRT1, PINK1, Parkin, PGC-1α, NRF1, NRF2, TFAM, TOmm20, COX4, 4HNE, SOD1, p62, LC3-II |
| Reported gene enrichment or functional enrichment | miR-34a-p53-SIRT1-PARP-1 | p53- miR-34a—SIRT1 | miR-34a-p53-SIRT1-PARP-1 | miR-29b-SIRT1-PGC-1α | miR-34a-SIRT1- HIF 1α | MIAT-miR-29b-SIRT1-PGC-1α | miR-34a-SIRT1 |
Study characteristics of seven primary articles that fulfilled the study inclusion criteria are summarized. ARHL, age related hearing loss; qRT-PCR, quantitative reverse transcription polymerase chain reaction; NQO1, NADH:quinone oxidoreductase 1; NAD+/NADH, nicotinamide adenine dinucleotide +/hydrogen; H2AX, histone H2A variant; SIRT1, sirtuin 1; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; HIF-1α, hypoxia-inducible factor 1-alpha; PINK1, PTEN induced kinase 1; PARP-1, poly (ADP-ribose) polymerase 1; MIAT, myocardial infarction associated transcript; NRF1/2, nuclear respiratory factor 1/2; TFAM, mitochondrial transcription factor A; TNF-α, tumor necrosis factor-α; TOmm20, translocase of outer mitochondrial membrane 20; COX4, cytochrome c oxidase subunit 4; 4HNE, 4-hydroxy-2-nonenal; SOD1, superoxide dismutase; NF-kB, nuclear factor kappa B; LC3-II, microtubule-associated protein light chain 3. β-Lap, β-lapachone; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; JC- 1,5,5’,6,6’-tetrachloro-1,1’,3,3’-tetramethyl-benzimidazolylcarbocyanine iodide (mitochondrial dye); H2-DCFDA,2’,7’dichlorodihydrofluorescein diacetate.