Mitochondrial Dysfunction and Autophagy in Hepatic Ischemia/Reperfusion Injury

Table 1

Summary of strategies to reduce I/R injury.

Therapeutic strategy	Proposed mechanism	Reference
Cyclosporin A	Inhibits MPT onset	[87]
ATG7, Beclin-1 overexpression	Increase autophagy	[27]
Carbamazepine	Blocks calpains and increases autophagy	[29]
Hemin	Increases HO-1; Decreases Ca overload and calpain activation; Increases autophagy	[88]
Cisplatin	Increases ATG7 and Beclin-1 to increase autophagy; Decreases HMGB1 secretion	[33]; [34]
Rapamycin	Increases autophagy	[35, 36]
Chronic lithium	Increases autophagy; Reduces inflammatory cytokines, neutrophil infiltration, and HMGB1 levels; GSK-3β inhibitor	[37]; [89]
Nutrient depletion	Increases autophagy; Reduces circulating HMGB1	[9, 27]; [90]
Glutathione	Antioxidant; reduces TNF-α levels	[91–93]
N-Acetylcysteine	Maintains glutathione	[91, 92]
Glycine	Hepatocyte plasma membrane stabilization	[13, 94]
Gadolinium chloride	Kupffer cell inhibition; reduces lipid peroxidation	[95]
Allopurinol	Xanthine oxidase inhibitor	[96–100]
Interleukin 6	Reduces TNF-α levels and attenuates inflammatory response	[101, 102]
Atorvastatin	TLR-4 downregulation and NF-κB downregulation	[103]
Butyrate	Decreases TLR-4 expression	[104]
SB216763	GSK 3β inhibitor, suppressing proinflammatory response; Inhibits MPT onset	[105]
Oleanolic acid	GSK-3β inhibitor	[106]
Ulinastatin	Decreases HMGB1 expression	[107]
Eritoran	TLR-4 antagonist	[108]
ICAM-1 antibody	Blocks neutrophil infiltration	[109]
Mac-1 antibody	Blocks neutrophil activity	[110]
Carbon monoxide	GSK-3β inhibitor	[111]
Cobalt protoporphyrin	HO-1 inducer	[112]
Isoflurane	Increases HO-1 activity	[113]
Erythropoietin	Increases HO-1 activity	[114]
Heme oxygenase-1	Increases autophagy; Decreases TNF-α mediated apoptosis; Inhibits TLR4; Maintains sinusoidal diameter and decreases platelet adhesion to sinusoids	[88]; [115]; [116]; [117]
Nitric oxide	Inhibits MPT onset; Prevents TNF-α and Fas ligand-mediated apoptosis; Vasodilator; Prevents platelet adhesion	[87]; [40]; [41]; [43]
S-Nitroso-N-acetylpenicillamine (SNAP)	NO donor	[41]
DETA NONOate	NO donor	[41]
Spermine NONOate	NO donor	[41]
Sildenafil	cGMP phosphodiesterase inhibitor	[45]
YC-1	Guanylyl cyclase activator	[45]
eNOS overexpression	Increases NO	[45]
17-β estradiol	Increases serum NO	[47]
Hydrogen sulfide	Increases serum NO	[48]
Sevoflurane	Increases iNOS expression; Decreases TNF-α, IL-1β, MCP-1, NF-κB liver expression, and caspase 3 activity	[49]; [118]
Remifentanil	Decreases apoptosis and myeloperoxidase activity; Increases superoxide dismutase and NO/iNOS expression	[119]
Ischemic preconditioning	Increases HO-1; Increases autophagy; Reduces apoptosis; Preserves and restores ATP	[58]; [57]; [59]; [55]
Intermittent clamping	Limits mitochondrial damage; Preserves and restores ATP	[69]
Remote ischemic preconditioning	Increases HO-1, IL-10, and MMP-8	[71]