Table 1.

FDA-approved Pharmacologic Agents Studying Ischemia-Reperfusion Injury in Rat Testicular Torsion-Detorsion Models. Arrows (↑ or ↓) indicate the direction of effect of the marker after the intervention is applied. [References are listed in Appendix 1].

Author	Year	Intervention	Route	Timing of intervention	Duration of ischemia (hours)	Timing of endpoint (after detorsion)	Oxidative Markers												Histology				Apoptosis and Necrosis	Hormonal profile	Fertility potential
							MDA (↓ = lowerMDA = less damage)	SOD (↑ = higher SOD = less damage)	tGSH/GPx/GST (↑ = higher level = less damage)	NO (↓ = lower NO = less damage)	TNF-α (↓ = lower TNF = less damage)	Caspase-3 (↓ = lower level = less damage)	IL-2/IL-6/IL-10 (↓ = lower IL = less damage)	Catalase (↓ =lower level = less damage)	TOS (↓ = lower level = less damage)	TAOS (↑ = higher level = less damage)	XO (↓ = lower XO = less damage)	MPO (↓ = lower MPO = less damage)	Johnsen Score (↑ = higher score = less damage)	Cosentino Score (↓ = lower score = less damage)	STD (↑ = higher score = less damage)	GET (↑ = higher score = less damage)	TUNEL (↓ = lower score = less damage)	Hormones (↑ = higher level = better profile)	Sperm parameters (↑ = higher level = better profile)
Comparative Studies - agent in red had a greater effect
Azizollahi, S	2011	Vitamin C versus dopamine, or both	Unclear	Unclear	4	Unclear	↓												↑		↑
Quintaes, IPP	2020	EGF versus decopressive fasciotomy with flap, or both	Subcutaneous	Immediately after detorsion	4	21 days													↑
Keseroglu, BB	2019	Ibuprofen versus metamizole versus paracetamol	Oral	60 mins after torsion	4	8 days	↓			↓								↓		↓
Semercioz, A	2017	Melatonin* or zinc, or both	Intra-peritoneal	3 weeks post-op	1	1 hour	↓		↑										↑					↑
Sekmenli, T	2017	Colchicine versus melatonin	peritoneal or oral	15 mins prior to detorsion	6	Unclear					↓		↓		↓	↑			↑				↓
Yurtcu, M	2009	Melatonin versus methylprednisolone	peritoneal (melatonin)	detorsion, 1 dose versus 7 doses	6	3 months													↑
Isikdemir, F	2014	Zileuton versus montelukast	Intra-peritoneal	30 mins prior to detorsion	1	3 hours	↓												↑
Salmasi, AH	2005	Morphine versus naltrexone, or both	Intravenous	Immediately prior to detorsion	1	4 hours	↓	↑	↑					↓					↑
Yuvanc, E	2018	Nebivolol versus Pheniramine maleate	Intra-peritoneal	60 mins prior to detorsion	2	4 hours									↓	↑			↑
Kostakis, ID	2017	Sildenafil versus erythropoeitin (low versus high dose)	Intra-peritoneal	60 mins after torsion	1.5	24 hours						↓							↑	↓
Dejban, P	2019	Sumatriptan versus GR-127935 (selective antagonist of 5HT1B/1D-R)	Intra-peritoneal	Unclear	1	7 days		↑			↓								↑	↓
Ameli, M	2018	Tadalafil versus verapamil, or both	Unclear	30 mins prior to detorsion	Unclear	24 hours	↓	↑	↑										↑		↑	↑		↑
Yildirim, C	2018	Tadalafil versus darbopoetin, or both	Intra-peritoneal	30 mins after torsion	2	30 mins						↓							↑	↓
Karagoz, MA	2018	Papaverine versus alprostadil	spermatic cord	Immediately after detorsion	4	14 days													↑	↓
Mertoglu, C	2010	Methylprednisolone versus heparin	Intra-peritoneal	30 mins prior to detorsion	2	2 hours	↓	↑	↑	↓				↓					↑
Ozmerdiven, G	2017	Tadalafil versus L-arginine, or both	Intra-peritoneal	30 mins prior to detorsion	3	4 hours			↑										↑
Single-Agent Studies
Un, H	2015	Aliskiren	Oral	30 mins prior to torsion	2	2 hours	↓	↑	↑	↓			↓								↑
Dogan, C	2016	Amlodipine	Intra peritoneal	30 mins prior to torsion	2	2 hours	↓	↑	↑		↓								↑
Hirik, E	2018	Anakinra	Intra-peritoneal	Unclear	4	4 hours	↓		↑				↓					↓
Gozukara, KH	2020	Colchicine	“Infusion”	30 minutes prior to detorsion	3	Unclear	↓	↑	↑			↓							↑		↑	↑	↓
Yazdani, I	2019	Cyclosporine	Intra-venous	30 and 90 mins after torsion	1	hours Histology at 24	↓	↑	↑			↓		↓						↓	↑		↓		↑
Dejban.P	2019	Dapsone	Intra-peritoneal	Unclear	1	7 days		↑			↓								↑
Hand,V	2010	Dexmedetomidine	Intra-peritoneal	30 mins after torsion	1	4 hours	↓			↓						↑							↓
Uguralp, S	2004	EGF on gelatin film	Testicular wrap	Immediately after detorsion	4	7 and 21 days	↓		↑										↑		↑
Rashed, FK	2013	Erythropoietin	Intra-venous	Immediately after torsion	2	7 days													↑	↓
Bozkurt, M	2020	Hydrogen sulfide	Intra-peritoneal	30 mins prior to detorsion	2	4 hours	↓	↑	↑	↓	↓								↑				↓
Dokmeci, D	2007	Ibuprofen	Oral	40 mins prior to detorsion	5	5 hours versus 7 days	↓			↓									↑		↑
Kazemi-Darabadi, S	2019	L-carnitine + betamethasone	Intra-peritoneal	Immediately after torsion	6	12 hours													↑		↑	↑			↑
Kurt, O	2016	Mannitol	“Infusion”	Immediately after torsion	3	2 hours	↓	↑	↑					↓			↓		↑		↑		↓
Yurtcu, M	2008	Melatonin*	Intra-peritoneal	15 mins prior to detorsion	6	7 days	↓												↑					↑
Ghasemnejad-Berenji, M	2018	Metformin	Unclear	Unclear	1	hours Sperm	↓	↑	↑			↓									↑		↓		↑
Yousefi-Manesh, H	2019	Modafinil	Intra-peritoneal	7 days post-op	1	7 days	↓				↓		↓						↑			↑
Acer-Demir, T	2019	N-acetylcysteine	Intra-tunica vaginalis	30 minutes prior to detorsion	3	30 days													↑	↓	↑	↑
Kazaz, 10	2019	N-acetylcysteine	Intra-peritoneal	30 minutes prior to detorsion	4	2 hours													↑				↓
Mestrovic, J	2014	Nifedipine	Intra-peritoneal	30 mins prior to detorsion	3	3 hours	↓	↑	↑														↓
Lee, JW	2019	Nitrous versus nitrous + C-PTIO (NO Scavenger)	Intra-venous	Unclear	5	24 hours	↓	↑				↓							↑		↑			↑
Ghasemnezhad, R	2015	Oxytocin	Intra-peritoneal	Immediately after detorsion	2	3 hours													↑			↑	↓	↑
Firat, F	2018	Oxytocin	Intra-peritoneal	30 mins prior to detorsion	3	3 hours	↓	↑	↑	↓									↑
Savas, C	2002	Pentoxifylline	Intra-peritoneal	15 mins prior to torsion	0.5	30 mins	↓													↓
Mahmoud, NM	2019	Pioglitazone	Intra-peritoneal	30 minutes prior to detorsion	4	4 hours	↓	↑	↑		↓	↓	↓		↓	↑				↓
Wei, SM	2017	Probucol	Intra-peritoneal	Immediately after detorsion	2	hours Histology at 3	↓											↓	↑
Urt Filho, A	2012	Propofol	Intra-peritoneal	45 mins after torsion	1	90 days															↑
Unsal, A	2004	Propofol	Intra-peritoneal	30 mins prior to detorsion	2	Unclear	↓		↑					↓			↓				↑
Zheng, N	2018	Rosiglitazone	Unclear	Unclear	2	24 hours	↓				↓		↓					↓		↓
Kara, O	2016	Selenium	Unclear	Unclear	3	Unclear	↓	↑	↑							↑			↑				↑
Jafari, A	2020	Topiramate	Unclear	30 mins prior to detorsion	1	5 hours	↓	↑	↑					↓					↑
Erol, B	2009	Vardenafil	Intra-peritoneal	30 mins after torsion	1	4 hours	↓			↓					↓				↑				↓
Tunckiran, A	2005	VEGF	Intra-testicular	Pre-torsion	2	2 months						↓							↑		↑	↑

Abbreviations are as follows: malonedialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), total glutathione (tGSH), glutathione S-transferase (GST), nitric oxide (NO), tumor necrosis factor-α (TNF-α), TOS (total oxidant status), TAOS (total anti-oxidant status), myeloperoxidase (MPO), transforming growth factor-beta (TGF-beta), xanthine oxidase (XO), STD (seminiferous tubule diameter), GET (germinal epithelium thickness), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).

^*on formulary at hospitals but not strictly FDA-approved