PMID- 25904243
OWN - NLM
STAT- MEDLINE
DCOM- 20160509
LR  - 20150703
IS  - 1600-079X (Electronic)
IS  - 0742-3098 (Linking)
VI  - 59
IP  - 1
DP  - 2015 Aug
TI  - Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats.
PG  - 70-9
LID - 10.1111/jpi.12241 [doi]
AB  - Hepatic mitochondrial dysfunction is thought to play a role in the development of 
      liver steatosis and insulin resistance, which are both common characteristics of 
      obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the 
      antioxidant properties of melatonin could potentially improve the impaired 
      functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic 
      fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg 
      BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and 
      C-ZL). Hepatic function was evaluated by measurement of serum alanine 
      transaminase and aspartate transaminase levels, liver histopathology and electron 
      microscopy, and hepatic mitochondrial functions. Several impaired functions of 
      hepatic mitochondria were observed in C-ZDF in comparison with C-ZL rats. 
      Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), 
      alleviates liver steatosis and vacuolation, and also mitigates diabetic-induced 
      mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves 
      mitochondrial dysfunction in M-ZDF rats by increasing activities of mitochondrial 
      citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) 
      and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) 
      (P < 0.01), and phosphorylation coefficient (ADP/O ratio) (P < 0.05). Also 
      melatonin augments ATP production (P < 0.05) and diminishes uncoupling protein 2 
      levels (P < 0.001). These results demonstrate that chronic oral melatonin reduces 
      liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be 
      beneficial in the treatment of diabesity.
CI  - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Agil, Ahmad
AU  - Agil A
AD  - Department of Pharmacology and Neurosciences Institute, School of Medicine, 
      University of Granada, Granada, Spain.
FAU - El-Hammadi, Mazen
AU  - El-Hammadi M
AD  - Department of Pharmacology and Neurosciences Institute, School of Medicine, 
      University of Granada, Granada, Spain.
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Damascus University, Damascus, 
      Syria.
FAU - Jimenez-Aranda, Aroa
AU  - Jimenez-Aranda A
AD  - Department of Pharmacology and Neurosciences Institute, School of Medicine, 
      University of Granada, Granada, Spain.
FAU - Tassi, Mohamed
AU  - Tassi M
AD  - Service of Microscopy, CIBM, University of Granada, Granada, Spain.
FAU - Abdo, Walied
AU  - Abdo W
AD  - Department of Pharmacology and Neurosciences Institute, School of Medicine, 
      University of Granada, Granada, Spain.
AD  - Department of pathology, Faculty of Veterinary medicine, Kafrelsheikh University, 
      Kafrelsheikh, Egypt.
FAU - Fernandez-Vazquez, Gumersindo
AU  - Fernandez-Vazquez G
AD  - Service of Endocrinology, La Paz Hospital, Madrid, Spain.
FAU - Reiter, Russel J
AU  - Reiter RJ
AD  - Department of cellular and Structural Biology, University of Texas Health Science 
      at San Antonio, San Antonio, TX, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150514
PL  - England
TA  - J Pineal Res
JT  - Journal of pineal research
JID - 8504412
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Diabetes Mellitus, Experimental/*drug therapy/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Liver/*metabolism
MH  - Melatonin/*therapeutic use
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria/*drug effects/*metabolism/pathology
MH  - Obesity/drug therapy/metabolism
MH  - RNA Interference
MH  - Rats
OTO - NOTNLM
OT  - ZDF rats
OT  - diabetes
OT  - liver
OT  - melatonin
OT  - mitochondria
OT  - obesity
EDAT- 2015/04/24 06:00
MHDA- 2016/05/10 06:00
CRDT- 2015/04/24 06:00
PHST- 2015/03/10 00:00 [received]
PHST- 2015/04/20 00:00 [accepted]
PHST- 2015/04/24 06:00 [entrez]
PHST- 2015/04/24 06:00 [pubmed]
PHST- 2016/05/10 06:00 [medline]
AID - 10.1111/jpi.12241 [doi]
PST - ppublish
SO  - J Pineal Res. 2015 Aug;59(1):70-9. doi: 10.1111/jpi.12241. Epub 2015 May 14.