Impaired induction of nerve ornithine decarboxylase activity in the streptozotocin-diabetic rat is prevented by the aldose reductase inhibitor ponalrestat.
1. The present study was designed to investigate if the aldose reductase inhibitor ponalrestat is capable of preventing the impairment of the response of ornithine decarboxylase (ODC) to nerve crush in streptozotocin (STZ)-diabetic rats. 2. ODC activity was measured in the dorsal root ganglia of crushed and uncrushed contralateral sciatic nerve of non-diabetic, ponalrestat-treated non-diabetic, STZ-diabetic and ponalrestat-treated STZ-diabetic rats. 3. Twenty four hours after crush, a significant (P less than 0.001) increase in the ratio of ODC activity in ganglia of crushed relative to uncrushed nerves was found in non-diabetic but not in diabetic rats, as expected. In the ponalrestat-treated diabetic rats the ratio was significantly higher (P less than 0.001) than that in the untreated diabetic rats and was not different from that in the non-diabetic group. 4. Ponalrestat also significantly decreased absolute levels of ODC activity in ganglia of uncrushed nerves from diabetic and non-diabetic animals. Despite the near-normal induction of ODC activity by nerve crush in the ponalrestat-treated diabetic animals, absolute ODC activity remained lower than that in ganglia of uncrushed nerves from non-diabetics. 5. We conclude that ponalrestat is able to prevent the impaired induction of ODC in experimental diabetes. The results, however, call into question the relationship between impaired ODC induction and diabetes-induced defects in nerve regeneration, which are insensitive to ponalrestat.
Pekiner
C
C
Department of Pharmacology and Therapeutics, University of Liverpool.
McLean
W G
WG
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010793:Phthalazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D010793:Phthalazines; C042829:ponalrestat; D000449:Aldehyde Reductase; D009955:Ornithine Decarboxylase