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PARP inhibition counteracts systemic oxidative stress and neural tissue 4‐hydroxynonenal adduct accumulation in experimental diabetic neuropathy
Author(s) -
Lupachyk Sergey,
Shevalye Hanna,
Maksimchyk Yury,
Drel Viktor,
Obrosova Irina G
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.831.12
Subject(s) - oxidative stress , 4 hydroxynonenal , medicine , diabetic neuropathy , chemistry , cancer research , endocrinology , diabetes mellitus , lipid peroxidation
We evaluated the role of poly(ADP‐ribose) polymerase (PARP) in systemic oxidative stress and 4‐hydoxynonenal adduct (4HNE) accumulation in diabetic peripheral neuropathy (DPN). Control and streptozotocin‐diabetic rats were maintained with or without treatment with the PARP inhibitor, 1,5‐isoquinolinediol, 3 mg kg‐1d‐1, for 10 weeks after initial 2 weeks. Treatment efficacy was evaluated by poly(ADP‐ribosyl)ated protein content in peripheral nerve, spinal, and DRG neurons and non‐neuronal cells, and indices of peripheral nerve function. Diabetic rats displayed increased urinary isoprostane and 8‐hydroxy‐2'‐deoxyguanosine excretion, 4HNE accumulation in peripheral nerve endothelial and Schwann cells, spinal cord neurons, astrocytes, and oligodendrocytes, and DRG neurons and glial cells, as well as motor and sensory nerve conduction velocity deficits, thermal hypoalgesia, and tactile allodynia. PARP inhibition counteracted diabetes‐induced systemic oxidative stress and 4‐hydroxynonenal adduct accumulation in peripheral nerve, spinal cord, and DRG neurons which correlated with improvement of peripheral nerve function. The findings reveal the important role of PARP activation in systemic oxidative stress and 4HNE accumulation in DPN.