TABLE 1.

In vivo and in vitro studies of TMP intervention AKI.

Type	Animal/Cell	Model	Inducer	TMP	Histological score	Markers	References
In vivo	ICR mice	ethanol-induced AKI	absolute ethanol	10, 25, 50 mg/kg; p.o.	No scoring	SrCr↓, BUN↓, MDA↓, Cytc↓	Liu et al. (2002)
In vivo	Wistar rats	I/R injury	renal artery clipping + reperfusion	4 ml/kg; i.v.	proximal convoluted tubule: 0 = normal; 1 = mitoses and necrosis of individual cells; 2 = necrosis of all cells in adjacent tubules; 3 = necrosis confined to the distal third of, necrosis across the inner cortex; 4 = necrosis affecting all three segments of tubule	MDA↓, SOD↑, ET-1↓	Sun et al. (2002)
In vivo	Wistar rats	I/R injury	hepatic/renal I/R	not clear; i.v.	No scoring	SrCr↓, BUN↓, P-selectin↓	Chen et al. (2003)
In vivo	C57BL/6 mice	I/R injury	right nephrectomy + left renal ischemia	80 mg/kg; i.p.	number of necrotic and apoptotic cells, loss of tubular brush border, tubular dilatation, cast formation, and neutrophil infiltration: 0 = none; 1=< 10%; 2 = 11–25%; 3 = 26–45%; 4 = 46–75%; 5=> 76%	SrCr↓, BUN↓, MDA↓, SOD↑, Bcl-2↑, ICAM-1↓	Feng et al. (2004)
In vivo	SD rats	ANP-AKI	sodium taurocholate	6 g/L; i.v.	tubular epithelial cells: 0 = normal; 1 = notable cloudy swelling; 2 = swelling denaturation, interstitial congestion, edema and infiltration of inflammatory cells; 3 = diffuse coagulation necrosis	SrCr↓, BUN↓, TXA2/PGI2↓	Zhang et al. (2006)
In vitro and In vivo	SD rats/NRK-52E cells	DI-AKI	gentamicin	80 mg/kg/d; i.p.	No scoring	Bcl-xL↑, TNF-α↓, NF-κB↓, caspase-3↓, caspase-8↓, caspase-9↓	Juan et al. (2007)
In vivo	Wistar rats	DI-AKI	cisplatin	80 mg/kg/d; p.o.	approximate extent of necrotic area in the cortical proximal tubules: 0 = no necrosis; 1 = a few focal necrotic spots; 2 = necrotic area about onehalf; 3 = necrotic spots about two-thirds; 4 = nearly all of the area necrotic	SrCr↓, BUN↓, GSH↑, NAG↓, SOD↑, TOX↑	Ali et al. (2008)
In vivo	SD rats	DI-AKI	Cisplatin	50, 100 mg/kg; i.p.	No scoring	SrCr↓, BUN↓, MDA↓, NAG↓, SOD↑, GSH↑, GST↑, NOS↓, NO↓	Liu et al. (2008)
In vivo	Wistar rats	DI-AKI	Gentamicin	100 mg/kg/d; p.o.	No scoring	SrCr↓, BUN↓, UNAG↓	Ali et al. (2009)
In vivo and In vitro	C57B6 mice/NRK-52E	DI-AKI	gentamicin	80 mg/kg/d; i.p.	tubular necrosis: 0 = normal; 1 ≤ 10%; 2 = 10–25%; 3 = 26–75%; 4 ≥ 75% cells exhibiting necrosis	HO-1↑, Bcl-xL↑, Hax-1↑, NADPH↓, NF-κB↓, Cox-2↓, caspases-3↓, caspases-9↓	Sue et al. (2009)
In vivo	C57BL/6 mice	I/R injury	renal artery clipping + reperfusion	80 mg/kg; i.p.	positive tubular brush border, tubular dilatation, cast formation, neutrophil infiltration: 0 = none; 1 = 10%; 2 = 11–25%; 3 = 26–45%; 4 = 46–75%; 5 = 76%	MPO↓, MDA↓, SOD↑, TNF-α↓, ICAM-1↓	Feng et al. (2011)
In vivo	Lewis rats	severe burn	30% TBSA scald injury	40 mg/kg/d; i.p.	expression of Bcl-2 and MICA: 0 = 0–5% stained; 1=> 5–25%; 2=> 25–50%; 3=> 50–75%; 4=> 75%	MDA↓, SOD↑, MICA↓, Bcl-2↓	Gao et al. (2012)
In vivo	SD rats	CIN	L-NAME + indomethacin + iohexol	80 mg/kg/d; i.p.	No scoring	SrCr↓, BUN↓, phospho-p38 MAPK↓, FoxO1↓, Bcl-2↑, Bax↓, iNOS↓, CysC↓, UNAG↓, UGGT↓	Gong et al. (2013)
In vivo	SD rats	DI-AKI	Cadmium chloride (CdCl2)	50 mg/kg; i.p.	No scoring	BUN↓, kim-1↓, indoxyl sulfate↓, clusterin↓, MDA↓, SOD↓, GR↓, LDH↓, ALP↓	Lan et al. (2014)
In vitro	HK-2 cells	DI-AKI	sodium arsenite	—	No scoring	ROS↓, GSH↑, β-catenin↓, NF-κB↓, p38 MAPK↓, COX-2↓, TNF-α↓, Cytc oxidase↑, mitochondrial membrane potential↑	Gong et al. (2015)
In vitro	HK-2 cells	DI-AKI	sodium arsenite	—	No scoring	HO-1↓, ARS2↓ p38 MAPK↓, JNK↓, AP-1↓, Nrf2↓, NF-κB↓	Gong et al. (2016)
In vivo	SD rats	DI-AKI	Cadmium chloride (CdCl2)	50 mg/kg; i.p.	No scoring	SrCr↓, BUN↓, MDA↓, 4-HNE↓, GSH↑, GSH/GSSG↑, SAM↑, cystathionine↑, MATs↑, CBS↑	Kuang et al. (2017)
In vivo	SD rats	CIN	L-NAME + indomethacin + iohexol	80 mg/kg/d; i.p.	No scoring	SrCr↓, BUN↓, Drp1↓, Mfn2↑, CCL2↓, CCR2↓, LC3B-II/I↓, Beclin-1↓, p62↑, procaspase 9↑, caspase 3↓, TNF-α↓, ROS↓, IL-6↓, CysC↓, UNAG↓, UGGT↓	Gong et al. (2019)
In vivo	SD rats	DI-AKI	Cisplatin	50, 100 mg/kg/d; i.p.	No scoring	SrCr↓, BUN↓, HMGB1↓, TLR4↓, NF-κB↓, TNF-α↓, IL-1β↓, GSH↑, SOD↑, PPAR-γ↑, Nrf2↑, Bax↓, Bcl2↑, caspase-3↓, HO-1↑, NQO1↑, COX-2↓, iNOS↓, Kim-1↓	Michel and Menze, (2019)
In vivo	C57BL/6 mice	Sepsis-AKI	cecal ligation and puncture (CLP)	10, 30, 60 mg/kg; i.v.	pathological changes of renal cortex or outer zone of medulla: 0 = normal; 1 = less than 5%; 2 = 5–25%; 3 = 25–75%; 4= > 75%	Kim1↓, caspase- 3↓, NMDAR1↓	Ying et al. (2020)
In vivo	SD rats	I/R injury	renal artery clipping + reperfusion	40 mg/kg; i.p.	renal tubular injury: 1 = normal; 2 = 0–10%; 3 = 11–25%; 4 = 26–45%; 5 = 46–75%; 6= > 75%	TNF-α↓, IL-1β↓, IL-6↓, MDA↓, GSH↑, LC3B-II/I↑, Beclin-1↑	Chen et al. (2020)
In vivo and In vitro	SD rats/NRK-52E cells	I/R injury	renal artery clipping + reperfusion/CoCl2/OGD + reoxygenation	40 mg/kg; i.p.	injury in tubules of the outer medulla: 0 = none; 1 = 0–10%; 2 = 11–25%; 3 = 26–45%; 4 = 46–75%; 5=> 75%	SrCr↓, BUN↓, NOD2↓, TNF-α↓, IL-6↓, MCP-1↓, caspase-3/cleaved caspase-3↓, LC3A/B-II/I↑	Jiang et al. (2020)
In vivo and In vitro	SD rats/NRK-52E cells	I/R injury	renal artery clipping + reperfusion/OGD + reoxygenation	200 mg/kg; p.o.	No scoring	SrCr↓, BUN↓, TNF-α↓, IL-6↓, NLRP3↓, HIF-1α↓, KIM-1↓	Sun et al. (2020)