Ethanol increases hepatic mitophagy driven by unknown mechanisms. Type 1 sequesters polarized mitochondria for nutrient recovery and cytoplasmic remodeling. In 2, mitochondrial depolarization (mtDepo) initiates to remove the damaged organelles. Previously, we showed that acute ethanol administration produces reversible mtDepo. Here, tested hypothesis ethanol-induced mtDepo 2 mitophagy. GFP-LC3 transgenic mice were gavaged with (2-6 g/kg) without pre-treatment agents decrease or increase...

The major side effect of cyclosporin A is severe nephrotoxicity. It likely that causes vasoconstriction leading to hypoxia-reperfusion injury; therefore, these experiments were designed attempt obtain physical evidence for hypoxia and free radical production in kidney following A. Rats treated daily with (25 mg/kg ig) 5 days, pimonidazole, a marker, was injected 2 h after the last dose α-(4-pyridyl-1-oxide)- N- tert-butylnitrone (4-POBN) 3 trap radicals. Cyclosporin doubled serum creatinine...

Injury to parenchymal and nonparenchymal cells of livers stored in cold Euro-Collins solution was assessed following reperfusion compared with graft survival orthotopic rat liver transplantation. Parenchymal maintained their viability nearly completely after up 24 hr storage as by trypan blue exclusion (97% cells) LDH release (4% total) from reperfused for 20 min storage. Furthermore, hepatic glycolysis (rates lactate plus pyruvate production), oxygen uptake NADH redox state...

Graft failure after liver transplantation may involve mitochondrial dysfunction. We examined whether prevention of injury would improve graft function. Orthotopic rat was performed 18 hours' cold storage in University Wisconsin solution and treatment with vehicle, minocycline, tetracycline, or N -methyl-4-isoleucine cyclosporin (NIM811) explants recipients. Serum alanine aminotransferase (ALT), necrosis, apoptosis were assessed 6 hours implantation. Mitochondrial polarization cell viability...

Liver resection is commonly performed under ischemic conditions, resulting in two types of insult to the remnant liver: ischemia reperfusion injury (IRI) and loss liver mass. Complement inhibition recognized as a potential therapeutic modality for IRI, but early complement activation products are also essential regeneration. We describe novel site-targeted murine inhibitor, CR2-CD59, which specifically inhibits terminal membrane attack complex (MAC), we use this protein investigate...

Our previous studies showed that an extract from Camellia sinenesis (green tea), which contains several polyphenols, attenuates nephrotoxicity caused by cyclosporine A (CsA). Since polyphenols are stimulators of mitochondrial biogenesis (MB), this study investigated whether stimulation MB plays a role in green tea polyphenol protection against CsA renal toxicity. Rats were fed powdered diet containing polyphenolic (0.1%) starting 3 days prior to treatment (25 mg/kg, i.g. daily for weeks)....

Background/Aims An increase of ethanol metabolism and hepatic mitochondrial respiration occurs in vivo after a single binge alcohol. Here, our aim was to determine how intake affects polarization status relation steatosis. Methods Hepatic polarization, permeability transition (MPT), reduce pyridine nucleotides, steatosis mice were monitored by intravital confocal/multiphoton microscopy the fluorescence rhodamine 123 (Rh123), calcein, NAD(P)H, BODIPY493/503, respectively, gavage with (1–6...

Destruction of Kupffer cells with gadolinium chloride (GdCl 3 ) and intestinal sterilization antibiotics diminished ethanol-induced steatosis in the enteral ethanol feeding model. However, mechanisms fatty liver remain unclear. Accordingly, role fat accumulation was studied. Rats were given (5 g/kg body wt) intragastrically, tissue triglycerides measured enzymatically. isolated 0–24 h after ethanol, PGE 2 production by ELISA, whereas inducible cyclooxygenase (COX-2) mRNA detected RT-PCR. As...

This study investigated the effects of glycine on reperfusion injury in a low-flow, reflow liver perfusion model. With this protocol, livers were perfused at low flow rates approximately 1 ml.g-1. min-1 for 75 min, which caused cells pericentral regions lobule to become anoxic because insufficient delivery oxygen. When normal (approximately 4 ml.g-1.min-1) restored 40 an oxygen-dependent occurred. Upon reflow, lactate dehydrogenase (LDH), cytosolic enzyme, and malondialdehyde (MDA), end...

The mitochondrial permeability transition (MPT) plays an important role in hepatocyte death caused by ischemia-reperfusion (IR). This study investigated whether activation of the cellular oxygen-sensing signal cascade prolyl hydroxylase inhibitors (PHI) protects against MPT after hepatic IR. Ethyl 3,4-dihyroxybenzoate (EDHB, 100 mg/kg ip), a PHI, increased mouse hypoxia-inducible factor-1α and heme oxygenase-1 (HO-1). EDHB-treated untreated mice were subjected to 1 h warm ischemia ∼70% liver...

The mitochondrial permeability transition (MPT) mediates hepatic necrosis after ischemia and reperfusion (I/R). Here, we studied the role of c-Jun N-terminal kinase 2 (JNK2) in MPT-induced liver injury. Wildtype (WT) JNK2 knockout (KO) mice underwent 70% for 1 hr followed by 8 hr, which hepatocyte injury animal survival was assessed. Compared with WT, KO had 38% less alanine transaminase release 39% histology. Survival out to 14 days also greater (57% vs. 11%), overall Kaplan-Meier improved....

These experiments were designed to determine whether green tea extract (GTE), which contains polyphenolic free radical scavengers, prevents ischemia-reperfusion injury the liver. Rats fed a powdered diet containing 0-0.3% GTE starting 5 days before hepatic warm ischemia and reperfusion. Free radicals in bile trapped with spin-trapping reagent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) measured using electron spin resonance spectroscopy. Hepatic increased transaminase release...

Accumulation of hydrophobic bile acids during cholestasis leads to generation oxygen free radicals in the liver. Accordingly, this study investigated whether polyphenols from green tea Camellia sinenesis, which are potent radical scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were fed a standard chow or diet containing 0.1% polyphenolic extracts C. sinenesis starting 3 days before duct ligation. After ligation, serum alanine transaminase increased 760 U/l after...

Although glycine prevents renal tubular cell injury in vitro, its effect vivo is not clear. The purpose of this study was to investigate whether a bolus injection given before reperfusion plus continuous dietary supplementation afterward would reduce caused by ischemia-reperfusion. Female Sprague-Dawley rats received semisynthetic powdered diet containing 5% and 15% casein (glycine group) or 20% (control group). Two days later, ischemia produced cross-clamping the left vessels for 15 min,...

Mitophagy (mitochondrial autophagy) in hepatocytes is an essential quality control mechanism that removes for lysosomal digestion damaged, effete and superfluous mitochondria. has distinct variants. In type 1 mitophagy, typical of nutrient deprivation, cup-shaped sequestration membranes (phagophores) grow, surround sequester individual mitochondria into mitophagosomes, often coordination with mitochondrial fission. After sequestration, the outer compartment mitophagosome acidifies entrapped...

ABSTRACT. Evidence has accumulated for a role of toxic oxygen radicals in the pathogenesis ischemia-reperfusion injury kidney. The aim this study was to evaluate hypothesis that reducing postischemic renal is possible by delivery gene antioxidant enzyme superoxide dismutase (SOD). Female Sprague-Dawley rats received intravenous injections recombinant adenovirus (1 × 109 pfu) containing transgenes Escherichia coli β-galactosidase (Ad-LacZ, as control) or human Cu/Zn-SOD (Ad-SOD). Three days...