Oxygen Free Radical Effects in Sciatic Nerve in Experimental Diabetes

Abstract

We previously reported the presence of endoneurial hypoxia, ischemia, impairment of the blood-nerve barrier, and reduction of norepinephrine and 6-ketoprostaglandin F1 alpha in chronic streptozocin-induced diabetic neuropathy (SDN) and interpreted these findings as suggesting the involvement of oxygen free radicals (OFRs) but did not directly measure indices of OFR activity. In this study, we report on sciatic nerve conjugated dienes, hydroperoxides, norepinephrine, and malondialdehyde in SDN at 1, 4, and 12 mo in male Sprague-Dawley rats. Severe hyperglycemia was present throughout in diabetic rats. Conjugated dienes were consistently increased at all time points, hydroperoxides were consistently reduced, and malondialdehyde was not significantly different in diabetes compared with controls. These findings are consistent with increased OFR activity in experimental diabetes. It is necessary to monitor several indices of OFR activity in a metabolically active tissue such as the peripheral nerve.

Comparison of the effects of aminoguanidine and L-carnitine treatments on somatosensorial evoked potentials in alloxan-diabetic rats

“…AG restored SEP latencies markedly at the 1st week and both compounds significantly improved SEP latencies at the 4th week of the treatment period. Although TBARS may give conflicting results (Low and Nickander 1991), it increases in the early period of STZ-induced diabetes (Low and Nickander 1991), and it has been reported to decrease by antioxidant agents such as butylated hydroxytoluene (Saulis-Liparota et al 1995). The SEP latency measured in our study reflects mainly the cortical conduction time, which consisted a main central and a very short peripheral component.…”

“…Raised levels of lipid peroxidation products as a result of oxidative stress have been reported both in human (Nishigaki et al 1981) and STZ -diabetic rats (Low and Nickander 1991;Pitchard et al 1986). Although the exact mechanisms of alloxan and STZ-induced diabetes are not well defined, and in fact may be different, the present study indicates that neuropathic changes emerging after induction with alloxan may share common characteristics with STZ -induced diabetes such as raised levels of lipid peroxidation products (Low and Nickander 1991). Although the exact mechanisms of alloxan and STZ-induced diabetes are not well defined, and in fact may be different, the present study indicates that neuropathic changes emerging after induction with alloxan may share common characteristics with STZ -induced diabetes such as raised levels of lipid peroxidation products (Low and Nickander 1991).…”

“…Excessive flux of glucose through polyol-pathway (Greene et al 1987;Winegrad 1987), increased glycation of structural proteins (Brownlee et al 1988;Kennedy and Baynes 1984), ischemic hypoxic insults (Dyck et al 1985;Low 1987) as well as decreased endoneural levels of acetyl-L-carnitine (ALC) and Lcarnitine (LC) (Stevens et al 1994;Ido et al 1994) may be implicated in the causation of diabetic neuropathy. 1986;Low and Nickander 1991). Several factors promote oxidative stress in diabetes, including nerve-ischemia-reperfusion (McCord 1985, Schmelzer et al 1989, increased free radical production caused by autooxidation reactions of sugars with proteins and unsaturated lipids (Baynes 1991), and impairment of tissue anti-oxidant protection systems (Loven at al.…”

Diabetic neuropathy in children

“…(2) depletion of myoinositol; (3) reduced activity of Na/K ATPase; (4) increased sorbitol levels; (5) reduced nerve growth factors; (6) increased free oxygen radicals (Low and Nickander, 1991); (7) abnormal mitochondrial function; (8) increased levels of glycated proteins (Jakus and Rietbrock, 2004;Hwang et al, 2005); (9) reduced production of various vasodilatory effectors leading to microangiopathy, tissue ischemia, and hypoxia; (10) activation of nuclear factor k B and protein kinase C that produces inflammatory damage (Vlassara, 1992;Brownlee, 2001); and (11) interaction between the multipotent immunemodulator CD40 ligand and its receptor contributing to further inflammatory insult to the nervous system (El-Asrar et al, 2012). Additional proposed mechanisms relate to direct insulin signaling on neurons and axons; C-peptide deficiency (a by-product of the insulin prohormone originally thought to be inactive); abnormal signaling by advanced glycation end products on neuronal and glial receptors; and activation of poly-ADP-ribose polymerase in microvessels and neurons (Zochodne, 2008;Verrotti et al, 2009).…”

Taurine Prevents Apoptosis Induced by High Ambient Glucose in Human Tubule Renal Cells

“…5 Taurine also has antioxidant properties, 4,9-11 which may explain its role as a scavenger of free radical production in diabetic tissue. 12 Previous studies have shown that taurine prevents glucose-induced lipid peroxidation and excess collagen production in mesangial cells. 13 Moreover, it has been observed that apoptosis is activated in rat 14 and murine tubular cells exposed to high glucose concentrations 2 and that taurine attenuates apoptosis induced by high glucose in human endothelial cells.…”