Chronic Lithium Treatment has Antioxidant Properties but does not Prevent Oxidative Damage Induced by Chronic Variate Stress

Abstract

This study evaluated the effects of chronic stress and lithium treatments on oxidative stress parameters in hippocampus, hypothalamus, and frontal cortex. Adult male Wistar rats were divided into two groups: control and submitted to chronic variate stress, and subdivided into treated or not with LiCl. After 40 days, rats were killed, and lipoperoxidation, production free radicals, total antioxidant reactivity (TAR) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were evaluated. The results showed that stress increased lipoperoxidation and that lithium decreased free radicals production in hippocampus; both treatments increased TAR. In hypothalamus, lithium increased TAR and no effect was observed in the frontal cortex. Stress increased SOD activity in hippocampus; while lithium increased GPx in hippocampus and SOD in hypothalamus. We concluded that lithium presented antioxidant properties, but is not able to prevent oxidative damage induced by chronic variate stress.

Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study

“…Animal studies report changes after treatment with Li in prefrontal cortex McGrath et al 2006), striatum (Kameda et al 2001;Senatorov et al 2004), cerebellum (Inouye et al 1995;Volonte et al 1994), and hypothalamus (de Vasconcellos et al 2006). The relatively short-term studies of Moore et al (2000a) and Sassi et al (2002) reported an increase in total grey matter, suggesting that the HC is not the only brain region that is sensitive to the effects of Li.…”

Lithium and cognitive enhancement: leave it or take it?

“…Chronic lithium also appears to protect from, and even reverse, some of the cognitive effects of chronic variate stress, such as the compromise of spatial reference memory in the water maze (Vasconcellos et al 2003(Vasconcellos et al , 2005. In the same paradigm, lithium presented antioxidant properties in the hippocampus (decrease of stress-induced free radicals production), though it was not able to prevent oxidative damage induced by chronic variate stress (Vasconcellos et al 2006b).…”

“…Therefore, the possibility that lithium has similar effects on other brain structures cannot be excluded. The variate stress regime used in the two studies mentioned above (Vasconcellos et al 2003(Vasconcellos et al , 2005 was also shown to cause oxidative damage in the hippocampus (Vasconcellos et al 2006b). Although chronic lithium presented some antioxidant properties (decreased free radicals production in hippocampus), it was not able to block the stress-induced oxidative damage (Vasconcellos et al 2006b).…”

Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

“…No alterations were seen for protein carbonyl formation in this model, and changes in antioxidant enzymes were variable (Frey et al, 2006d). Others have supported the antioxidant effects of lithium, but have not found it able to prevent stress-induced oxidative damage in rats (de Vasconcellos et al, 2006). Treatment with valproate has been shown to inhibit lipid peroxidation and protein oxidation in primary cultured rat cerebrocortical cells exposed to an oxidant (Wang et al, 2003).…”