Table 1.

Small molecules that target mitochondria effectively prevent the cardiotoxicity induced by Dox.

Name of Molecules	Model	Key Mechanisms of the Action Against Dox	Anti-Cancer Effect	Refs.
AA	NRC, rats	↓Disruption of ΔΨm	-	[24]
		↓Mitochondrial apoptotic pathway
Baicalein	Chick cardiomyocytes	↓Disruption of ΔΨm	↔	[25,26,27,28]
		↓ROS
		↓JNK activation
Berberine	NRC, MCF-7 cells, rats	↓Mitochondrial dysfunction	↑	[29,30,31,32,33,34]
		↓Disruption of ΔΨm
		↓Mitochondrial apoptotic pathway
		↓Mitochondrial Ca2+
		↓Dox metabolize
Curcumin	Rats, Mice H9c2	↑Mitochondrial KATP channel	-	[35,36,37,38,39,40]
		↓Mitochondrial phosphate carrier
		↓Mitochondrial superoxide radicals
CRY	Rats	↑Mitochondrial biogenesis	-	[41]
		↑Activities of mitochondrial respiratory chain complex
Chrysin	Rats	↓Mitochondrial apoptotic pathway	-	[42]
		↓MAPK and NF-κB activation
		↑VEGF/AKT pathway
CVB-D	Mice	↑Mitochondrial biogenesis	-	[43]
CBD	Mice, rats	↑Mitochondrial function	-	[13,44]
		↑Mitochondrial biogenesis
		↓Pro-inflammatory response
Esculetin	H9c2	↑Mitochondrial function	-	[45]
		↑Bmi-1 expression
		↓ROS
HKL	Mice	↑Cardiac mitochondrial respiration	↔	[46,47]
		↑Sirt3
		↑PPARγ
HT	Rats	↑Mitochondrial dysfunction	-	[48]
		↑Mitochondrial electron transport chain
Isorhamnetin	H9c2, rats, MCF-7, HepG2 and Hep2	↓Mitochondria-dependent apoptotic Pathway	↑	[49]
		↓MAPK pathway
		↓ROS
Kaempferol	H9c2, rats	↓Mitochondrial dysfunction	↑	[50,51]
		↓Disruption of ΔΨm
		↓Mitochondrial apoptotic pathway
LUTG	H9c2	↓Disruption of ΔΨm	↕	[52,53]
Myricitrin	H9c2, rats	↓Disruption of ΔΨm	-	[54]
		↓Mitochondrial apoptotic pathway
		↓ROS
Naringin	H9c2, rats	↓Disruption of ΔΨm	-	[55,56]
		↓P38 MAPK
		↓ROS
OMT	H9c2, rats	↓Mitochondrial apoptotic pathway	-	[57,58]
		↓ROS
OP-D	H9c2, mice	↓Disruption of ΔΨm	-	[59]
		↓Autophagy and ROS
PD	H9c2	↓Disruption of ΔΨm	-	[60]
		↓ROS
		↓NF-κB activation
Quercetin	H9c2, mice	↓Mitochondrial dysfunction	-	[61,62,63,64]
		↓Disruption of ΔΨm
		↓ROS
		↑Bmi-1 expression
RV	NRC	↓Disruption of ΔΨm	-	[65,66,67]
		↑Sirt1 pathway
		↓ROS
RA	H9c2	↓Disruption of ΔΨm	-	[68,69]
		↓ROS
Ses	H9c2, rats	↓Disruption of ΔΨm	-	[70]
		↑Sirt1 and Mn-SOD pathway
Sulforaphane	H9c2, NRC, rats	↑Nrf2	↑	[71,72]
		↓Disruption of ΔΨm
		↓Mitochondrial apoptotic pathway
SAI	Rats	↓Membrane sclerosis	↔	[73,74]
	L1210 cells
Tetrandrine	Rats	↑Mitochondrial function	↑	[75]
		↓Mitochondrial oxidative phosphorylation
THSG	Mice, NRC	↓Disruption of ΔΨm	↑	[76,77]
		↓Mitochondrial apoptotic pathway
		↓ROS
Visnagin	Zebrafish, Mice, NRC, HL1, MCF7, DU145, LNCaP, MDA-MB-231	↓Mitochondrial malate dehydrogenase 2 activity	↔	[78,79]
ALA	Rats	↓Mitochondrial apoptotic pathway	-	[80,81]
		↑Nrf2
ATRA	H9c2	↑Mitochondrial function	↑	[82,83]
		↓Mitochondrial biogenesis damage
BAY60-2770	H9c2, rats	↓ROS	-	[84,85]
		↓Disruption of ΔΨm
		↑Mitochondrial ferritin
Ghrelin	NRC, H9c2, mice	↓Disruption of ΔΨm	-	[86,87,88]
		↑mitochondrial bioenergetics
		↓Mitochondrial apoptotic pathway
Melatonin	H9c2, rats	↑Mitochondrial biogenesis	↑	[89,90]
	NIH3T3 cells	↑PPARγ
		↓ROS
D006	H9c2, zebrafish	↓mitochondrial biogenesis	↑	[91]
	MCF-7
Mdivi-1	Rats, NRC, HL60	↓Mitochondrial fission	↔	[92,93]
STS	Mice, Rats	↓Mitochondrial lipid peroxidation and swelling	-	[94,95]
Bafilomycin A1, rapamycin	H9c2, mice	↑Autophagy	↔	[96]
		↓ROS
		↑Mitochondrial function
Diazoxide	Rats, mice	↑Mitochondrial KATP channel	-	[97,98,99]
		↑Mitochondrial connexin
Dxz	NRC, Rats	↓Mitochondrial iron accumulation	↔	[11,100,101]
	Mice	↓Mitochondrial DNA
Met	Mice, rats	↑Mitochondrial function	↑	[102,103,104]
	HL-1	↓Mitochondrial apoptotic pathway
	MCF7/ADR
Nicorandil	Rats, HL-1	↑Mitochondrial function	↔	[105,106,107]
		↓Mitochondrial apoptotic pathway
		↑Mitochondrial creatine kinase activity and oxidative phosphorylation capacity
		↑Mitochondrial KATP channel
Sildenafil	Mice, mouse cardiomyocytes	↑Mitochondrial KATP channel	↑	[108,109,110]
		↓Disruption of ΔΨm

↑, increase or open; ↓, decrease or inhibit; ↔, no difference; -, no description; ↕, biphasic effect; ΔΨm, mitochondrial membrane potential; NRC, Neonatal rat cardiomyocytes.