TY - JOUR
T1 - Evaluation of orally active poly(ADP-Ribose) polymerase inhibitor in streptozotocin-diabetic rat model of early peripheral neuropathy
AU - Li, F
AU - Szabo, C
AU - Pacher, P
AU - Southan, GJ
AU - Abatan, OI
AU - Charniauskaya, T
AU - Stevens, Martin
AU - Obrosova, IG
PY - 2004/4/1
Y1 - 2004/4/1
N2 - AIMS/HYPOTHESIS: Poly(ADP-ribose) polymerase activation depletes NAD+ and high-energy phosphates, activates protein kinase C, and affects gene expression in various tissues. This study was designed to characterise the effects of the potent, orally active poly(ADP-ribose) polymerase inhibitor PJ34 in the Wistar rat model of early diabetic neuropathy. METHODS: Control and streptozotocin-diabetic rats were maintained with or without PJ34 treatment (30 mg x kg(-1) x day(-1)) for two weeks, after two weeks without treatment. Endoneurial blood flow was assessed by hydrogen clearance; metabolites and high-energy phosphates were assayed by enzymatic spectrofluorometric methods; and poly(ADP-ribose) was detected by immunohistochemistry. RESULTS: Blood glucose concentrations were increased to a similar extent in untreated and PJ34-treated diabetic rats compared with controls. Intense poly(ADP-ribose) immunostaining was observed in the sciatic nerve of diabetic rats, but not in other groups. Final sciatic motor nerve conduction velocity and digital sensory nerve conduction velocity were reduced by 24% and 22% respectively in diabetic rats compared with controls (p
AB - AIMS/HYPOTHESIS: Poly(ADP-ribose) polymerase activation depletes NAD+ and high-energy phosphates, activates protein kinase C, and affects gene expression in various tissues. This study was designed to characterise the effects of the potent, orally active poly(ADP-ribose) polymerase inhibitor PJ34 in the Wistar rat model of early diabetic neuropathy. METHODS: Control and streptozotocin-diabetic rats were maintained with or without PJ34 treatment (30 mg x kg(-1) x day(-1)) for two weeks, after two weeks without treatment. Endoneurial blood flow was assessed by hydrogen clearance; metabolites and high-energy phosphates were assayed by enzymatic spectrofluorometric methods; and poly(ADP-ribose) was detected by immunohistochemistry. RESULTS: Blood glucose concentrations were increased to a similar extent in untreated and PJ34-treated diabetic rats compared with controls. Intense poly(ADP-ribose) immunostaining was observed in the sciatic nerve of diabetic rats, but not in other groups. Final sciatic motor nerve conduction velocity and digital sensory nerve conduction velocity were reduced by 24% and 22% respectively in diabetic rats compared with controls (p
UR - http://www.scopus.com/inward/record.url?scp=2442651710&partnerID=8YFLogxK
U2 - 10.1007/s00125-004-1356-0
DO - 10.1007/s00125-004-1356-0
M3 - Article
C2 - 15298348
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
SN - 1432-0428
VL - 47
SP - 710
EP - 717
JO - Diabetologia
JF - Diabetologia
ER -
