Elsevier

Neuroscience Letters

Volume 351, Issue 3, 20 November 2003, Pages 137-140
Neuroscience Letters

Reactive oxygen species play an important role in iodoacetate-induced neurotoxicity in primary rat neuronal cultures and in differentiated PC12 cells

https://doi.org/10.1016/S0304-3940(03)00858-9Get rights and content

Abstract

The role of reactive oxygen species in the pathogenesis of the neurotoxicity associated with ischemia-reperfusion, was investigated in a model of primary rat neuronal cultures and of differentiated PC12 cells, subjected to chemical ischemia by iodoacetic acid (IAA, 2.5 h) followed by a short period of reperfusion (1 h). The injury to the cells was assessed by lactate dehydrogenase (LDH) release into the culture media. The PC12 cells exhibited relative resistance to IAA cytotoxicity. Therefore these cells were studied at a 4-fold higher IAA concentration (400 μM instead of 100 μM for the neurons). The injury to both cell types was significantly greater in the short post-insult reperfusion (PIR) period than during the insult period. The presence, during the combined insult and PIR periods, of α-tocopherol (100 μM), melatonin (1 mM) and LY231617 (5 μM), conferred to both cell types considerable protection against the injury occurring during the insult and during the PIR periods (assessed separately). Superoxide dismutase (SOD; 500 IU/ml) conferred protection to the neurons, but not to the PC12 cells. When exposure to the antioxidants was limited to the short (15 min) pre insult period, only LY231617 conferred protection. In the neurons the protection occurred only during the insult period, whereas in the PC12 cells during both the insult and PIR periods. When the exposure to the antioxidants was limited to the PIR period, only SOD conferred protection and only in the neuronal cultures. These findings suggest that neuronal damage caused during ischemia-reperfusion can be diminished markedly by co-presence of antioxidants during the insult period. Certain antioxidants may protect the neurons even when present only before or after the insult.

References (19)

There are more references available in the full text version of this article.

Cited by (29)

  • Alpha tocopherol treatment reduces the expression of Nogo-A and NgR in rat brain after traumatic brain injury

    2013, Journal of Surgical Research
    Citation Excerpt :

    Alpha-tocopherol, a member of the vitamin E family, reacts with free radicals, capturing unpaired electrons and effectively eliminating their ability to damage nerve tissue cells [23]. Vitamin E has been used in the treatment of TBI, with some success [24–26]. Raicević et al [27] administered oral vitamin E to patients in the acute phase of TBI and found that intracellular calcium overload was reduced, inhibiting neuronal mitochondria swelling.

  • Flavonoids protect retinal ganglion cells from ischemia in vitro

    2008, Experimental Eye Research
    Citation Excerpt :

    IAA has been used previously to induce ischemia in primary cultures of chick retinal cells (Ferreira et al., 1997; Rego et al., 1999a) as well as primary cortical neurons (Sperling et al., 2003) and cerebellar granule cells (Malcolm et al., 2000). The changes observed following IAA treatment of neural cells are very similar to changes which have been seen in animal models of retinal ischemia (Osborne et al., 2004) and include alterations in membrane potential (Reiner et al., 1990), breakdown of phospholipids (Taylor et al., 1996), loss of ATP (Sperling et al., 2003; Winkler et al., 2003) and an increase in reactive oxygen species (ROS) (Sperling et al., 2003; Taylor et al., 1996). As a test of this approach to identifying compounds that might protect RGCs from ischemia, we decided to focus on flavonoids, polyphenolic compounds widely distributed in fruits and vegetables (for reviews see Heim et al., 2002; Middleton et al., 2000; Ross and Kasum, 2002).

View all citing articles on Scopus
View full text