Hair Cell Protection from Ototoxic Drugs

Table 1

Potential drug targets for treatment of AG and cisplatin ototoxicity.

Compound	Ototoxic drug	Mechanism	Materials and methods	References
ORC-13661	AG and cisplatin	Block MET channel	Mouse cochlear cultures, in vitro zebrafish, in vitro	[41]
Copper sulfate	Cisplatin	CTR1 inhibitor, inhibit uptake	HEI-OC1 cells, in vitro; Mice, in vivo, i.t.	[31]
Cimetidine	Cisplatin	OCT blocker, inhibit uptake	Mice, in vivo, i.p.	[34]
Coenzyme Q10	Cisplatin	Antioxidant	Rat, in vivo, oral administrations	[55]
α-Lipoic acid	AG	Antioxidant	Guinea pigs, in vivo, i.m.	[56]
D-Methionine	AG	Antioxidant	Guinea pigs, in vivo, i.p.	[57]
Thiourea	Cisplatin	Antioxidant	Guinea pigs, in vivo, intracochlear perfusion by osmotic pump	[58]
Vitamins B, C, and E	Cisplatin	Antioxidant	Rat, in vivo, i.p.	[59]
N-Acetylcysteine	AG	Antioxidant	Rat, in vivo, i.p.	[60]
Hormone melatonin	Cisplatin	Antioxidant	Rat, in vivo, i.p.	[61]
siRNA	Cisplatin	Inhibit TRPV1 or NOX3; Inhibit ROS generation and STAT1 activation	UB/OC-1 cells, in vitro; Rat, in vivo, i.t.	[62]
2,3-Dihydroxybenzoate	AG	Iron chelators; Compete with AG for iron binding	Guinea pigs, in vivo, i.p.	[64]
Acetylsalicylate	AG	Iron chelators, compete with AG for iron binding; Antioxidant	Guinea pigs, in vivo, oral administration	[65]
EGCG	Cisplatin	STAT1 inhibitor; Antiapoptotic	Rat, in vivo, oral administrations	[79]
Bay 11-7085	Cisplatin	NF-κB inhibitors; Inhibit caspase-3 activation	HEI/OC1 cells, in vivo	[78]
SN-50	Cisplatin	NF-κB inhibitors; Inhibit caspase-3 activation	HEI/OC1 cells, in vivo	[78]
z-VAD-FMK	AG	General caspase inhibitor	Guinea pigs, in vivo, intracochlear perfusion by osmotic pump	[81]
z-LEHD-FMK	AG	Caspase-9 inhibitor	Guinea pigs, in vivo, intracochlear perfusion by osmotic pump	[81]
z-DEVD-fmk	Cisplatin	Caspase-3 inhibitor	Guinea pigs, in vivo, intracochlear perfusion by minipump	[48]
z-LEHD-fmk	Cisplatin	Caspase-9 inhibitor	Guinea pigs, in vivo, intracochlear perfusion by minipump	[48]
CEP-1347	AG	JNK inhibitor	Guinea pigs, in vivo, s.c.	[97]
CEP 11004	AG	JNK inhibitor	Chicken vestibular hair cell culture, in vitro	[91]
Pifithrin-a	Cisplatin	p53 inhibitor; Inhibit mitochondrial apoptotic pathway	Mouse cochlear culture, in vitro	[100]

AG: aminoglycoside; MET: mechanoelectrical transducer; CTR1: Copper Transporter 1; OCT: organic cation transporter; siRNA: short interfering RNA; TRP: transient receptor potential; NOX3: NADPH-oxidase 3; ROS: reactive oxygen species; STAT1: transcription factor; EGCG: epigallocatechin gallate; JNK: c-jun NH2-terminal kinase; i.t.: intratympanic; i.p.: intraperitoneal; i.m.: intramuscular; s.c.: subcutaneous.