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Oxidative stress, with reactive oxygen intermediate formation, may represent a common mechanism by which liver injury is induced by diverse etiologies. Oxidative stress enhances nuclear factor kappa B (NF-kappa B) activity, and NF-kappa B activity has been shown to enhance the expression of cytotoxic cytokines. Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice. This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of alpha-tocopherol. Alpha-tocopherol treatment of the mice given the CCl4 also reduced the NF-kappa B binding to levels approaching those found in normal mice. In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced NF-kappa B binding and an increase in tumor necrosis factor-alpha (TNF-alpha) messenger RNA levels. Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-kappa B binding activity in comparison with the binding of normal livers. These data demonstrate that abolishing acute hepatic injury with alpha-tocopherol, a free radical scavenger, also eliminated increased NF-kappa B binding. It is tempting to speculate that enhanced NF-kappa B expression caused by free radical production/oxidative stress may modulate liver injury, perhaps through an effect on cytotoxic cytokine synthesis.

Lysosomal storage diseases (LSDs) are a group of genetic disorders that result from defective lysosomal metabolism or export of naturally occurring compounds. Signs and symptoms are variable both within and between disorders depending on the location and extent of storage. Many patients develop neurologic symptoms that become obvious from the newborn period to adulthood. Diagnosis of suspected patients can usually be made by measuring the activity of an enzyme or concentration of a metabolite in easily obtained tissue samples. Based on the considerable diagnostic experience of our laboratory, we aid the physician in selecting the appropriate tests to perform. Hematopoietic stem cell transplantation and enzyme replacement therapy are already available or in clinical trials for a number of LSDs. Early diagnosis is critical, especially since those patients who are treated before significant symptoms arise have the best chance for a positive outcome.

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