Table 1.

In vitro and in vivo studies on the effect of astaxanthin on oxidative stress-associated diseases and mitochondrial dysfunction.

	Experimental Model	Effective Dose and Duration	Main Results	Reference
Inflammatory Diseases	Human umbilical vein endothelial cells (HUVECs) treated with H2O2	10 μM 48 h	cell viability ↑ reactive oxygen species (ROS) ↓ mitochondrial membrane potential (MMP) ↑	[40]
	Preeclamptic pregnant rats	25 mg/kg 16 days	blood pressure ↓ urinary protein ↓ oxidative stress marker; malondialdehyde (MDA) ↓ serum superoxide dismutase (SOD) ↑ histopathological changes ↓ preeclampsia-associated protein ↓ heme oxygenase-1 ↑ caspase-3 ↓ nuclear factor-κB (NF-κB) ↓	[40]
	Alveolar epithelial cells type II (AECs-II) from rats with bleomycin-induced lung fibrosis	1, 2 mg/kg 7 days	apoptosis ↓ SOD, catalase activities ↑ mitochondrial membrane integrity ↑ mitochondria swelling ↓ deformed cristae ↓	[43]
	Rat lung epithelial -T-antigen negative (RLE-6TN) cells treated with H2O2 or bleomycin	8 μM 6–24 h	apoptosis ↓ ROS ↓ SOD, catalase activities ↑ mitochondrial membrane integrity ↑ mitochondria swelling ↓ deformed cristae ↓ mitochondria disarrangement ↓ MMP ↑ pro-apoptotic protein ↓ anti-apoptotic protein ↑ cytochrome c release, caspase activation ↓ nuclear factor erythroid-derived 2-related factor 2 (Nrf2) ↑ p53 ↑	[43]
	A classic “comb” burn model in rats	5, 10, 20 mg/kg 48 h	burn-associated histological changes ↓ inflammatory cell infiltration ↓ oxidative stress marker (MDA) ↓ SOD, glutathione peroxidase ↑ xanthine oxidase, NADPH oxidase ↓ myeloperoxidase, TNF-α, IL-1β, IL-6 ↓ apoptosis ↓ activated cellular homolog of murine thymoma virus akt8 oncogene (Akt) ↑ inactivated Bcl-2-associated death promoter (Bad) protein ↑	[50]
	Severe burn rat model	5, 10, 20 mg/kg 24 h	histological and functional damage of kidney ↓ oxidation-reduction potential ↓ oxidative stress marker (MDA) ↓ SOD, catalase ↑ apoptosis ↓ activated Akt, inactivated Bad ↑ cytochrome c, caspases ↓	[51]
Aging	Geriatric dogs	20 mg/kg 16 weeks	oxidative stress markers (8-hydroxy-2′-deoxyguanosine, protein carbonyl, nitric oxide) ↓ blood SOD ↑ mitochondrial mass ↑ ATP production ↑ mitochondria Complex III production ↑	[41]
	Senescence accelerated mice (SAM)	8% of antioxidant diet 10 months	plasma glutathione (GSH) ↑ glutathione disulfide (GSSG) ↓ mitochondrial GSH in kidney, heart, brain, skeletal muscle ↑ ,mitochondrial GSSG in liver, kidney, heart, brain ↓ mitochondrial glutathione redox potential ↑	[57]
	Rats with d-galactose-induced brain aging	0.02% 8 weeks	oxidative stress markers (MDA, 8-hydroxy-2′-deoxyguanosine, protein carbonyls) in brain ↓ brain glutathione peroxidase, SOD activities ↑ total antioxidant capacity ↑ anti-apoptotic protein ↑ pro-apoptotic protein ↓ cyclooxygenase (COX)-2 ↓ brain-derived neurotrophic factor ↓	[59]
Cardiovascular Diseases	BALB/c mice	0.02, 0.08% 8 weeks	cardiac MMP ↑ TNF-α ↓ contractility of left ventricle ↑	[54]
	Human umbilical vein endothelial cells (HUVECs) exposed to glucose fluctuation	0.05, 0.1, 0.5 μM 3 days	ROS ↓ a component of NADPH oxidase p22phox ↓ endogenous nitric oxide synthase (eNOS) ↑ nitrite ↓ peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α ↑ IL-6, intercellular adhesion molecule-1 ↓ apoptosis ↓ phosphorylation of c-Jun N-terminal kinases (JNK), p-38 ↓	[55]
	Rats with isoproterenol hydrochloride-induced myocardial infarction	25 mg/kg 2 weeks	heart and kidney wet weight ↓ oxidative stress markers (MDA, nitric oxide) ↓ heart SOD, catalase, GSH ↑ histopathological changes ↓	[56]
	Mice with left anterior descending coronary artery (LAD) occlusion-induced ischemia-reperfusion injury	50 mg/kg 2 h	infarct size ↓ pro-apoptotic protein ↓ anti-apoptotic protein ↑ mitochondrial ROS ↓ cardiac mitochondria depolarization ↓ cardia mitochondria swelling ↓ oxidative stress marker (MDA) ↓	[42]
	H9c2 rat myocardial cells exposed to homocysteine	4 μM 6 h	cell viability ↑ apoptosis ↓ MMP ↑ mitochondria fragmentation ↓ pro-apoptotic protein ↓ anti-apoptotic protein ↑ intracellular ROS, mitochondrial ROS ↓ DNA damage ↓	[44]
	Homocysteine administered mice	5 mg/kg 4 weeks	GSH ↑ oxidative stress marker (MDA) ↓ apoptosis ↓	[44]
Neuro-degenerative Diseases	Human neuroblastoma SH-SY5Y cells treated with 6-hydroxydopamine	20 μM 30 min	apoptosis ↓ cytochrome c release, caspase-9 cleavage, caspase-3 activation ↓ p38 ↓ MMP ↑	[45]
	Human neuroblastoma SH-SY5Y cells treated with 6-hydroxydopamine or DHA hydroperoxide	100 nM 4 h	cell viability ↓ apoptosis ↓ cytochrome c release ↓ MMP ↑ oxidative stress marker (protein carbonyls) in mitochondrial fraction ↓ ROS ↓	[46]
	Human neuroblastoma SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+)	50 μM 25 h	cell viability ↑ apoptosis ↓ ROS ↓ SOD, catalase ↑ pro-apoptotic protein ↓ anti-apoptotic protein ↑ cytochrome c release, caspase activation ↓ MMP ↑	[47]
	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson’s disease	30 mg/kg 28 days	dopaminergic neurons ↑ histological hallmarks of Parkinson’s disease ↓	[47]
	Mouse neural progenitor cells treated with H2O2	10 ng/mL 8 h	apoptosis ↓ cell proliferation ↑ caspase activation ↓ ATP production ↑ mitochondrial leakage ↓ pro-apoptotic protein ↓ p38 ↑	[60]
	Primary cortical neuron treated with H2O2	500 nM 4 h	cell viability ↑ apoptosis ↓ MMP ↑	[61]
	Rats with middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia	50, 80 mg/kg 6 h	infarct volume ↓ neurological deficit score ↓	[61]
Liver Diseases	Nonalcoholic steatohepatitis (NASH) mice fed high-fat, cholesterol, and chocolate diet	0.02% 12 weeks	liver AST, ALT ↓ triglyceride, total cholesterol, non-esterified fatty acid ↓ hepatic lipid accumulation ↓ oxidative stress marker (MDA) ↓ lipogenic gene expression ↓ glucose intolerance ↓ hyperinsulinemia ↓ hepatic insulin signaling proteins ↓ JNK, p38, NF-κB ↓ infiltration and activation of Kupffer cells ↓ hepatic fibrosis ↓	[63]
	Rat model of ischemia-reperfusion injury	5 mg/kg 14 days	Histopathological score ↓ cell damage ↓ xanthine dehydrogenase: xanthine oxidase ratio ↑ mitochondrial swelling ↓ rough endoplasmic reticulum disarrangement ↓	[65]
	High fat- high fructose diet -induced mice obesity model	6 mg/kg 45 days	body weight ↓ hepatomegaly ↓ plasma glucose ↓ plasma liver lipid ↓ oxidative stress markers (MDA, nitrite nitrosothiol) ↓ SOD, catalase, glutathione peroxidase, glutathione s-transferase ↑ TGF-β1 ↓ histological abnormality ↓	[66]
	Rats intoxicated with CCL4	10 mg/kg 2 weeks	liver AST, ALT, alkaline phosphatase ↓ oxidative stress markers (MDA, nitric oxide) ↓ SOD, catalase activities ↑ myeloperoxidase ↓ inflammatory cell infiltration ↓ liver tissue necrosis ↓ hepatic fibrosis ↓	[67]
Metabolic Complications	Porcine proximal tubular epithelial cells (PTECs) exposed to high glucose	5, 10 μg/mL 24–48 h	cell viability ↑ cytotoxicity ↓ pro-apoptotic protein ↓ anti-apoptotic protein ↑ reactive nitrogen species (RNS) (•O2, NO•, ONOO–) ↓ oxidative stress marker (MDA) ↓ COX-2, inducible nitric oxide synthase (iNOS), NF-κB ↓	[73]
	Alloxan-induced diabetic rat model	20 mg/kg 30 days	blood glucose, blood triglyceride ↓ pro-reducing redox balance of plasmalymphocyte oxidative stress marker (MDA) ↓ lymphocyte ROS/RNS (H2O2, •O2, NO•) ↓ calcium influx of lymphocytes ↓	[74]
	Normal human mesangial cells (NHMCs) treated with high glucose	10−6 M 24 h	mitochondrial ROS ↓ activator protein-1 activation ↓ monocyte chemoattractant peptide-1, COX-1, TGF-β1 ↓ lipid peroxidation in mitochondria ↓ mitochondrial protein adducts ↓ NF-κB ↓	[75]
	Streptozotocin-induced diabetic rats	10, 20, 40 mg/kg 5 days	body weight ↓ blood glucose ↓ oxidative stress marker (MDA) in cerebral cortex and hippocampus ↓ SOD, GSH ↑ eNOS, iNOS ↓ NF-κB, TNF-α, IL-1β, IL-6 ↓ caspase ↓ phosphoinositide 3-kinase/Akt ↑	[77]