Experimental Diabetic Neuropathy Oxidative Stress and Antioxidant Therapy

AST A Meclica AWD GmbH, Frankfurt, Germany James D. Schmelzer, Yutaka Kishi, Yoshiyuki Mitsui, Masaaki Nagamatsu, Kim K. Nickander, Paula J. Zollman, and Phillip A. Low Mayo Foundation, Rochester, Minnesota There is ample evidence of oxidative stress in both experimental (EDN) and human diabetic neuropathy. Most studies have been done on plasma, with limited study on neural tissues. We briefly review and update our studies. I. MECHANISMS OF OXIDATIVE STRESS A. Endoneurial Ischemia Hypoxia There...

Mechanisms Of Hyperglycemiainduced Pkc Activation

In association with the diabetic vascular complications, increased total DAG content has been demonstrated in a variety of tissues, including retina (16), aorta, heart (17), and renal glomeruli (18,19), in both diabetic animal models and patients (Table 1). This has also been observed in classically termed insulin-sensitive tissues such as the liver and skeletal muscle (20,21). In all vascular cells studied, increasing glucose levels from 5 to 22 mM in the media elevated the cellular DAG...

A Aladin Study

The improvement in neuropathic symptoms during a 3-week period of intravenous treatment with 600 mg a-lipoic acid day as compared with vitamin B, (26) in conjunction with the recent experimental evidence (15) formed the rationale for a large-scale, 3-week, multicenter, randomized, double-blind, placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy ALADIN) (27). Assuming from previous studies a placebo response of about 30 and a drug response of about 60 , the a priori estimate of...

Summary And Conclusion

In the foregoing discussion we have tried to define the nature of OxS and then, using that definition, to assess the status of OxS in diabetes. Based on analysis of various biomarkers of OxS in long-lived proteins, we conclude that OxS is not overtly or systemically increased in diabetes, except at later stages in the development of complications. Metabolic derangements in diabetes lead to an increase in concentration of oxidizable substrates and compromised detoxification pathways. The...

B Dekan Study

An effective treatment aimed at improving or retarding the progression of reduced HRV, the hallmark and earliest sign of CAN, might potentially favorably influence the poor prognosis among these patients. The efficacy and safety of a-lipoic acid were studied in a randomized, double-blind, placebo-controlled, multicenter trial (Deutsche ATardiale Autonome Neuropathic DEKAN Study) in NIDDM patients with CAN (32). Inclusion criteria were age > 18 and < 70 years, NIDDM treated with diet, oral...

References

Nerve blood flow and oxygen delivery in normal, diabetic, and ischemic neuropathy. Int Rev Neurobiol 1989 31 355438. 2. Brook WH. Postural hypotension and the anti-gravity suit. Aust Fam Physician 1994 23 1948, 1948-1949. 3. Cameron NE, Cotter MA, Low PA. Nerve blood flow in early experimental diabetes in rats relation to conduction deficits. Am J Physiol 1991 261 E1-E8. 4. Tuck RR, Schmelzer JD, Low PA. Endoneurial blood flow and oxygen tension in the sciatic...

Interactions Between Antioxidants And Essential Fatty Acids

Most of the preceding discussion has dealt with effects of ROS on the NO system and cell-signaling pathways. Another major ROS target is the polyun- saturated fatty acids, including the essential fatty acids necessary for eicosa-noid production and normal membrane structure and fluidity. ROS subject these important molecules to self-propagating destructive chain reactions initiated by lipid peroxidation. A. Essential Fatty Acids, Diabetes, and Neurovascular Dysfunction The most common dietary...

D 2d Da

Figure 3 Reversal of sciatic nutritive endoneurial blood flow (A) and motor conduction velocity (B) deficits in diabetic rats by treatment with the probucol analogue BM 150639. Groups (n 9-10) C, nondiabetic control ID, 2D, 1-month, and 2-month streptozotocin-diabetic DA, 1-month untreated diabetes followed by 1-month BM 150639 (400 mg kg day) treatment DAN, as for DA but cotreated with the nitric oxide synthase inhibitor, A' -nitro-L-arginine (10 mg kg day) during the second month. Data are...

C Aladin 3 Study

This was a randomized, double-blind, placebo-controlled, multicenter trial including type 2 diabetic outpatients with symptomatic distal symmetric polyneuropathy. Patients were allocated to three parallel groups receiving a-lipoic acid or placebo group 1 (n 167), a-lipoic acid 600 mg intravenously for 3 weeks, followed by a-lipoic acid 600 mg three times a day orally for 6 months group 2 (n 174), a-lipoic acid 600 mg intravenously for 3 weeks, followed by placebo orally for 6 months group 3 (n...

Pathways of Glucose Mediated Oxidative Stress in Diabetic Neuropathy

Obrosova, Martin J. Stevens, and Eva L. Feldman University of Michigan Medical Center, Ann Arbor, Michigan Diabetic distal symmetric sensorimotor polyneuropathy (DPN), the most common peripheral neuropathy in developed countries (1-3), affects up to 6070 of diabetic patients (4) and is the leading cause of foot amputation (5). The typical slowing of nerve conduction and the advancing distal symmetrical sensorimotor deficits are thought to reflect an underlying slowly...