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Autism Studies and Related Medical Conditions, January 2009 - TACA

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nutritional, <strong>and</strong> toxic status in autism are consistent with greater oxidative stress.<br />

3. Describe how anti-oxidant nutrients are used in the contemporary treatment<br />

of autism.<br />

McGinnis, W. R. (2005). "Oxidative stress in autism." Altern Ther Health Med 11(1): 19.<br />

McGinnis, W. R. (2007). "Could oxidative stress from psychosocial stress affect<br />

neurodevelopment in autism?" J <strong>Autism</strong> Dev Disord 37(5): 993-4.<br />

Miller, D. M. <strong>and</strong> J. S. Woods (1993). "Urinary porphyrins as biological indicators of<br />

oxidative stress in the kidney. Interaction of mercury <strong>and</strong> cephaloridine." Biochem<br />

Pharmacol 46(12): 2235-41.<br />

Reduced porphyrins (hexahydroporphyrins, porphyrinogens) are readily oxidized<br />

in vitro by free radicals which are known to mediate oxidative stress in tissue<br />

cells. To determine if increased urinary porphyrin concentrations may reflect<br />

oxidative stress to the kidney in vivo, we measured the urinary porphyrin content<br />

of rats treated with mercury as methyl mercury hydroxide (MMH) or<br />

cephaloridine, both nephrotoxic, oxidative stress-inducing agents. Rats exposed<br />

to MMH at 5 ppm in the drinking water for 4 weeks showed a 4-fold increase in<br />

24-hr total urinary porphyrin content <strong>and</strong> a 1.3-fold increase in urinary<br />

malondialdehyde (MDA), an established measure of oxidative stress in vivo.<br />

Treatment with cephaloridine alone (10-500 mg/kg, i.p.) produced a dose-related<br />

increase in urinary MDA <strong>and</strong> total porphyrin levels up to 1.6 <strong>and</strong> 7 times control<br />

values, respectively. Injection of MMH-treated rats with cephaloridine (500<br />

mg/kg) caused a synergistic (20-fold) increase in urinary porphyrin levels, but an<br />

additive (1.9-fold) increase in the MDA concentration. <strong>Studies</strong> in vitro<br />

demonstrated that cephaloridine stimulated the iron-catalyzed H2O2-dependent<br />

oxidation of porphyrinogens to porphyrins in the absence of either microsomes<br />

or mitochondria. Additionally, porphyrinogens were oxidized to porphyrins in an<br />

iron-dependent microsomal lipid peroxidation system. Moreover, porphyrinogens<br />

served as an effective antioxidant (EC50 approximately 1-2 microM) to lipid<br />

peroxidation. These results demonstrate that MMH <strong>and</strong> cephaloridine<br />

synergistically, as well as individually, promote increased oxidation of reduced<br />

porphyrins in the kidney <strong>and</strong> that this action may be mechanistically linked to<br />

oxidative stress elicited by these chemicals. Increased urinary porphyrin levels<br />

may, therefore, represent a sensitive indicator of oxidative stress in the kidney in<br />

vivo.<br />

Ming, X., M. A. Cheh, et al. (2008). "Evidence of oxidative stress in autism derived from<br />

animal models." American Journal of Biochemistry <strong>and</strong> Biotechnology 4(2): 218-225.<br />

<strong>Autism</strong> is a pervasive neurodevelopmental disorder that leads to deficits in social<br />

interaction, communication <strong>and</strong> restricted, repetitive motor movements. <strong>Autism</strong><br />

is a highly heritable disorder, however, there is mounting evidence to suggest<br />

that toxicant-induced oxidative stress may play a role. The focus of this article<br />

<strong>Autism</strong> <strong>Studies</strong> & <strong>Related</strong> <strong>Medical</strong> <strong>Conditions</strong> – <strong>TACA</strong> © Page 89

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