Back to Search
Start Over
Melatonin pretreatment enhances the therapeutic effects of exogenous mitochondria against hepatic ischemia-reperfusion injury in rats through suppression of mitochondrial permeability transition
- Source :
- Journal of Pineal Research. 61:52-68
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
Abstract
- We tested the hypothesis that melatonin (Mel) enhances exogenous mitochondria (Mito) treatment against rodent hepatic ischemia-reperfusion (IR) injury. In vitro study utilized three groups of hepatocytes (i.e. nontreatment, menadione, and menadione-melatonin treatment, 4.0 × 10(5) each), while in vivo study used adult male Sprague Dawley rats (n = 40) equally divided into sham-control (SC), IR (60-min left-lobe ischemia + 72-hr reperfusion), IR-Mel (melatonin at 30 min/6/8 hr after reperfusion), IR-Mito (mitochondria 15,000 μg/rat 30 min after reperfusion), and IR-Mel-Mito. Following menadione treatment in vitro, oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (cleaved caspase-3/PARP), DNA damage (γ-H2AX/CD90/XRCC1), mitochondria damage (cytosolic cytochrome c) biomarkers, and mitochondrial permeability transition were found to be lower, whereas mitochondrial cytochrome c were found to be higher in hepatocytes with melatonin treatment compared to those without (all P < 0.001). In vivo study demonstrated highest liver injury score and serum AST in IR group, but lowest in SC group and higher in IR-Mito group than that in groups IR-Mel and IR-Mel-Mito, and higher in IR-Mel group than that in IR-Mel-Mito group after 72-hr reperfusion (all P < 0.003). Protein expressions of inflammatory (TNF-α/NF-κB/IL-1β/MMP-9), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (caspase-3/PARP/Bax), and mitochondria damage (cytosolic cytochrome c) biomarkers displayed an identical pattern, whereas mitochondria integrity marker (mitochondrial cytochrome c) showed an opposite pattern compared to that of liver injury score (all P < 0.001) among five groups. Microscopically, expressions of apoptotic nuclei, inflammatory (MPO(+) /CD68(+) /CD14(+) cells), and DNA damage (γ-H2AX(+) cells) biomarkers exhibited an identical pattern compared to that of liver injury score (all P < 0.001) among five groups. Melatonin-supported mitochondria treatment offered an additional benefit of alleviating hepatic IR injury.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Apoptosis
Mitochondria, Liver
Mitochondrion
medicine.disease_cause
Mitochondrial Membrane Transport Proteins
Rats, Sprague-Dawley
Melatonin
03 medical and health sciences
0302 clinical medicine
Endocrinology
Internal medicine
medicine
Animals
Liver injury
biology
Mitochondrial Permeability Transition Pore
Liver Diseases
Cytochrome c
medicine.disease
Rats
Oxidative Stress
030104 developmental biology
Gene Expression Regulation
Liver
Biochemistry
Mitochondrial permeability transition pore
Reperfusion Injury
biology.protein
Reperfusion injury
030217 neurology & neurosurgery
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 07423098
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- Journal of Pineal Research
- Accession number :
- edsair.doi.dedup.....d4b17489b2651feadac87c2750bb6a86