|
| Pharmacological therapy |
| Liver transplantation and warm hepatic ischemia |
| Drug | Specie | Experimental model | Ischemic time | Effect |
|
| Chlorpromazine (Ca2+ channel antagonist) | Rat | Liver transplantation | 24 h | ↑ ATP, ↓ mitochondrial dysfunction and alterations in lipid metabolism |
| Tauroursodeoxy-cholate |
Rat | Liver transplantation | 8 h | ↓ Endoplasmic reticulum stress |
| Warm ischemia + hepatectomy | 1 h |
| Cbz-Val-Phe methyl ester (calpain inhibitor) | Rat | Liver transplantation | 24, 40 h | ↓ Calpain activation and SEC apoptotic |
| Tocopherol (antioxidant) |
Rat | Liver transplantation | 5 h | ↓ Lipid peroxidation, ↓ SEC damage and microcirculatory disturbances |
| Warm ischemia | 45, 90 min |
| Glutathione (antioxidant) |
Rat | Warm ischemia | 60, 90 min | ↓ Microcirculatory disturbances, ↑ detoxification of ROS, |
| Liver transplantation | 24 h |
| SOD (antioxidant) |
Rat | Warm ischemia | 45 min and 1 h | ↓ Microcirculatory disturbances and leukocyte accumulation |
| Liver transplantation | 8 h |
| Allopurinol (XOD inhibitor) |
Rat, Mice | Liver transplantation | 8, 16 h | ↓ Oxidative stress |
| Warm ischemia | 30, 60 min |
| Bucillamine (antioxidant) | Rat | Liver transplantation | 24 h | ↓ Oxidative stress |
| AMPK activators | Rat | Warm ischemia | 90 min | ↑ NO, and ATP |
| Adenosine | Rat | Warm ischemia | 90 min | ↑ NO |
| N-acetylcysteine (glutathione precursor) | Rat | Liver transplantation | 24 h | ↓ Microcirculatory disturbances |
| L-arginine (NO precursor) |
Rat | Liver transplantation | 18 h | ↑ ATP, ↑ NO, ↓neutrophil accumulation |
| Warm ischemia | 45 min |
| Spermine NONOate (NO donor) | Rat | Warm ischemia | 60, 90 min | ↓ IL-1α and oxidative stress |
| FK 409 (NO donor) | Rat | Liver transplantation | 80 min | ↓ SEC damage, ↓ IL-1 ↑ HSP, and IL-10 |
| EHNA (adenosine deaminase inhibitor) | Rat | Liver transplantation | 24, 44 h | ↑ Interstitial adenosine, ↓ leukocytes rolling and microcirculatory disturbances |
| CGS-21680 (adenosine A2 receptor agonist) | Rat | Liver transplantation | 30 h | ↓ SEC killing, ↑ cAMP |
| Anti-TNF antiserum |
Rat | Liver transplantation | 6, 24 h | ↓ TNF and leukocyte accumulation |
| Warm ischemia | 90 min |
| FR167653 (IL-1β and TNFα suppressor) | Rat | Liver transplantation | 48 h | ↓ TNF and IL1-α and Kupffer cell activation |
| IL-10 | Rat | Warm ischemia | 60 min | ↓ IL-1 and oxidative stress |
| Anti-ICAM-1 |
Rat | Liver transplantation | 24 h | ↓ Adherence of leukocytes in postsinusoidal venules |
| Warm ischemia | 1 h |
| PSGL-1 (P-selectin blocker) | Rat | Liver transplantation | 6 h | ↓ Neutrophil infiltration, ↓ INFγ, TNFα and iNOS |
| CS1 peptides (FN-α4β1 interaction blocker) | Rat | Liver transplantation | 4 h | ↓ Neutrophil and lymphocyte T infiltration, ↓ TNFα and iNOS |
| sCR1 (complement inhibitor) | Rat | Liver transplantation | 24 h | ↓ Microcirculatory disturbances, ↓ leukocyte adhesion |
| Sodium ozagrel (thromboxane synthase inhibitor) | Pig | Liver transplantation | 8 h | ↓ ET-1 |
| Glycine (Kupfer cell modulator) | Rat | Liver transplantation | 24 h | ↓ TNFα and neutrophil accumulation |
| GdCl3 (Kupffer cell blocker) | Rat | Liver transplantation | 24 h | ↓ TNFα and neutrophil accumulation, |
| Z-DEVD-FMK (caspase 3 and 7 inhibitor) | Rat | Liver transplantation | 16 h | ↓ Apoptosis, ↑ microvascular perfusion and Bcl-2 |
| Cobalt-protoporphyrin IX (HO-1 inducer) | Rat | Liver transplantation | 6 h | ↓ T-cell and macrophages infiltration |
| ANP (vasodilating peptide) | Rat | Liver transplantation | 24 h | ↓ Apoptosis, ↑ PI3K/Akt |
| Hemin (HO-1 inducer) | Rat | Liver transplantation | 6 h | ↑ Bcl-2 |
| Cerulenin (fatty acid synthase inhibitor) |
Mice | Warm ischemia | 15 min | ↓ UCP2, ↑ ATP |
| Liver transplantation | 80 min |
| Doxorubicin (heat shock proteins inducer) | Rat | Liver transplantation | 48 h | ↓ TNFα, MIP-2 and NFκB |
| Catalase and derivatives | Mice | Warm ischemia | 30 min | ↓ Oxidative stress |
| Rosiglitazone (PPAR-α agonist) | Rat | Warm ischemia | 30, 60, 90 min | ↑ Autophagy, ↓ cytokines |
| Apocynin (NAPH oxidase inhibitor) | Mice | Warm ischemia | 30 min | ↓ Oxidative stress |
| TBC-1269 (PAN selectin) | Mice | Warm ischemia | 90 min | ↓ Inflammatory response, ↓ ERK 1/2 |
| Melatonin (hormone) | Rat | Warm ischemia | 40 min | ↓ IKK and JNK pathways |
| Ascorbate (ROS scavenger) | Rat | Warm ischemia | 30 min | ↓ Apoptosis |
| FK506 (Immunosuppressant) | Rat | Warm ischemia | 60, 90 min | ↓ TNF |
| Gabexate mesilate (Protease inhibitor) | Rat | Warm ischemia | 60 min | ↓ Leukocyte activation, ↓ TNFα |
| OP-2507 (Analogue of prostacyclin) | Rat | Warm ischemia | 60 min | ↓ Microcirculatory disturbances |
| WY-14643 (PPAR-α agonist) | Rat | Warm ischemia | 60 min | ↓ Inflammatory cytokines, ↓oxidative stress |
| α-Lipoic acid (Antioxidant) | Rat | Warm ischemia | 90 min | ↓ Apoptosis, ↑ liver regeneration |
| Sirolimus (Immunossupressant) | Rat | Warm ischemia + hepatectomy | 60 min | ↓ Linfocytes |
| IL-1ra (IL-1 receptor antagonist) | Rat | Warm ischemia + hepatectomy | 90 min | ↓ TNF and oxidative stress |
| FK 3311 (Cox-2 Inhibitor) | Dog | Warm ischemia | 60 min | ↓ Cox-2, ↓ neutrophil infiltration |
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