Hepatoprotective effects of melatonin against pronecrotic cellular events in streptozotocin-induced diabetic rats
2014
Autori:
Grigorov, IlijanaBogojević, Desanka
Jovanović Stojanov, Sofija
Petrović, Anja
Ivanović Matić, Svetlana
Zolotarevski, Lidija
Poznanović, Goran
Martinović, Vesna
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
,
© University of Navarra 2014
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Oxidative stress-mediated damage to liver tissue underlies the
pathological alterations in liver morphology and function that are
observed in diabetes. We examined the effects of the antioxidant action
of melatonin against necrosis-inducing DNA damage in hepatocytes of
streptozotocin (STZ)-induced diabetic rats. Daily administration of
melatonin (0.2 mg/kg) was initiated 3 days before diabetes induction and
maintained for 4 weeks. Melatonin-treated diabetic rats exhibited
improved markers of liver injury (P<0.05), alkaline phosphatase, and
alanine and aspartate aminotransferases. Melatonin prevented the
diabetes-related morphological deterioration of hepatocytes, DNA damage
(P<0.05), and hepatocellular necrosis. The improvement was due to
containment of the pronecrotic oxygen radical load, observed as
inhibition (P<0.05) of the diabetes-induced rise in lipid peroxidation
and hydrogen peroxide increase in the liver. This was accompanied by
improved necrotic markers of cellular damage: a significant reduction in
cleavage of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1)
into necrotic 55- and 62-kDa fragments, and inhibition of
nucleus-to-cytoplasm translocation and accumulation in the serum of the
high-mobility group box 1 (HMGB1) protein. We conclude that melatonin is
hepatoprotective in diabetes. It reduces extensive DNA damage and
resulting necrotic processes. Melatonin application could thus present a
viable therapeutic option in the management of diabetes-induced liver
injury.
Ključne reči:
Diabetes; Liver necrosis; MelatoninIzvor:
Journal of Physiology and Biochemistry, 2014, 70, 2, 441-450
DOI: 10.1007/s13105-014-0322-7
ISSN: 1877-8755