Nerve conduction and antioxidant levels in experimentally diabetic rats: effects of streptozotocin dose and diabetes duration.
Oxidative stress supposedly plays a role in the pathogenesis of diabetic neuropathy. We have studied whether a variation in the streptozotocin (STZ) dose or diabetes duration affects the outcome of measurements of oxidative damage in relation to nerve conduction. In experiment 1, we induced diabetes in rats using 40 or 60 mg/kg STZ intravenously and assessed sciatic nerve conduction velocity. After 18 weeks, we measured plasma malondialdehyde (MDA) and red blood cell (RBC) and nerve glutathione levels. We observed a dose-dependent effect of STZ on body weight, and to a lesser extent on nerve conduction, but not on RBC or nerve glutathione and plasma MDA. In experiment 2, we administered a fixed dose of STZ (40 mg/kg) and measured antioxidants and MDA in RBCs, plasma, and sciatic nerve after 2, 4, 8, and 18 weeks in diabetic and control rats. RBC glutathione decreased in diabetic animals initially, but did not differ from control values after week 4. Plasma total glutathione increased until week 8. The ratio of total to oxidized glutathione in the sciatic nerve from diabetic animals paralleled the decrease observed in RBCs, and subsequently increased compared with controls. Nerve catalase increased in diabetic animals. Endoneurial MDA remained unchanged, whereas plasma MDA increased and RBC superoxide dismutase (SOD) decreased in the diabetic group. We conclude that differences in antioxidant levels between STZ-diabetic and control rats depend on the duration of hyperglycemia. Furthermore, dose-related effects of STZ on nerve conduction are not reflected in endoneurial lipid peroxidation or glutathione.
Van Dam
P S
PS
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, The Netherlands.
Van Asbeck
B S
BS
Bravenboer
B
B
Van Oirschot
J F
JF
Marx
J J
JJ
Gispen
W H
WH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D008297:Male; D009431:Neural Conduction / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000378:metabolism; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D001786:Blood Glucose; D013311:Streptozocin