Table 1.

Detail information of different drug for crush syndrome therapy.

Drug category	Drug/strategy	Protective mechanism	Specie	Author	Author Country	Journal Year	References
Chemical drugs	Mitochondria-targeted anti-oxidants (SkQR1)	Anti-oxidant, activate ischemia pre-processing signal pathway	- Rat	Koyner et al. Plotnikov et al.	USA Russia	2008 2011	[17,18]
	Dexamethasone	Anti-inflammatory, reduce IRI through the PI3K-Akt-eNOS signal pathway	Rat Rat Rat	Murata et al.	Japan	2016 2015 2013	[24–26]
	Allopurinol	Reduce oxidative stress, inhibit apoptosis, reduce inflammatory cell infiltration, increase cell proliferation	Rat	Gois et al.	Brazil	2016	[42]
	Nitrite	Inhibit IRI relate to NO	Rat Rat -	Murata et al.	Japan	2012 2017 2018	[47–49]
	Anisodamine	Activate α7nAChR, reduce serum potassium, inhibit HMGB1	Mouse Rat	Yu et al. Fan et al.	China China	2019 2016	[54,55]
	Astragaloside-IV	Anti-oxidant, prevent mitochondrial dysfunction and inflammation response	Rat	Murata et al.	Japan	2017	[67]
	Hydrogen sulfide (H2S)	Anti-inflammatory, anti-oxidant, and anti-apoptotic	Rat	Teksen et al.	Turkey	2019	[73]
	Bardoxolone methyl (BM)	Anti-inflammatory, anti-oxidant, anti-apoptotic	Rat	Kadioglu et al.	Turkey	2019	[76]
	N-(2-hydroxyphenyl) acetamide	Downregulate (COX-2, NF-κB , iNOS), upregulate (HO-1, KIM-1), aiti-inflammatory, anti-oxidant, retain the renal tubule brush border and actin cytoskeleton	Mouse	Siddiqui et al.	Pakistan	2019	[81]
	Ulinastatin	Reduce inflammation, regulate the balance between Th17 and Treg cells	Rat	Yang et al.	China	2020	[85]
Biological agents	Recombinant human erythropoietin (rhEPO)	Inhibit NF-κB and iNOS, regulate TLR4/NF-κB to promote M2 macrophages phenotypes	Rat Mouse Mouse	Yang et al. Wang et al. Zhou et al.	Taiwan China China	2012 2017 2020	[91,92,93]
	Macrophage surface molecule Mac-1 inhibitor: Lactoferrin (Lf)	Prevent platelet-mediated MET formation and related renal tubular injury	Mouse	Okubo et al.	Japan	2018	[97]
Antibody treatment	Anti-HMGB1 antibody	Blocking HMGB1, reduce inflammatory response and renal cortical cell apoptosis	Rat Mouse	Shimazaki et al. Zhang et al.	Japan China	2012 2017	[15,104]
	Anti-RAGE Antibody	Reduce inflammatory response, prevent the development of MOF	Rat	Matsumoto et al.	Japan	2017	[106]
Cell therapy	Mesenchymal stem cells (MSC) treatment	Promote M2 macrophages phenotype	- Mouse	Almeida et al. Duffy et al. Geng et al.	Brazil Ireland	2013 2014 2014	[110,111,112]
	Carbon monoxide-enriched red blood cell (CO-RBC)	Reduce the oxidation, degrade cytochrome P450, inhibit free heme and hemoglobin	Rat	Taguchi et al.	Japan	2020	[114]
Other treatment	Icing treatment	Inhibiting the increase of blood potassium concentrations and suppress acute inflammation reaction	Rat	Murata et al.	Japan	2020	[115]

Abbreviation: SkQR1: Mitochondria-targeted anti-oxidants; IRI: ischemia/reperfusion injury; H₂S: hydrogen sulfide; BM: Bardoxolone methyl; COX-2: Cyclooxygenase-2; NF-κB: Nuclear factor kappa-B; iNOS: Inducible nitric oxide synthase; HO-1: Heme oxygenase-1; KIM-1: Kidney injury molecule-1; rhEPO: Recombinant human erythropoietin; HMGB1: High mobility group box 1 protein; RAGE: Receptor for advanced glycation endproducts; MOF: multiple organ failure; MSC: Mesenchymal stem cells; CO-RBC: Carbon monoxide-enriched red blood cell.