Glutathione, a cysteine-containing tripeptide, is the most abundant nonprotein thiol in mammalian cells. Glutathione plays an important role in the detoxification of xenobiotic compounds and in the antioxidation of reactive oxygen species and free radicals. Because of its multiple functions in various tissues and its involvement in many diseases and malnutrition, a clear understanding of the interrelationships among tissue glutathione, nutrition, and oxidative stress is clinically relevant. The focus of this review is to discuss the regulation of tissue glutathione concentration by diet and nutritional status, and to apply this information to those diseases and malnutrition in which decreased tissue glutathione and increased oxidative stress are implicated. A potential strategy to rapidly restore glutathione for both antioxidant and immune defense systems before therapeutic treatment in malnourished patients is discussed.Key words: glutathione, dietary regulation, oxidative stress, malnutrition.

Although zinc (Zn) deficiency has been associated with insulin resistance, and altered Zn metabolism (e.g., hyperzincuria, low-normal plasma Zn concentrations) may be present in diabetes, the potential effects of Zn on modulation of insulin action in Type II diabetes have not been established. The objective of this study was to compare the effects of dietary Zn deficiency and Zn supplementation on glycemic control in db/db mice. Weanling db/db mice and lean littermate controls were fed Zn-deficient (3 ppm Zn; dbZD and InZD groups), Zn-adequate control (30 ppm Zn; dbC and InC groups) or Zn-supplemented (300 ppm Zn; dbZS and InZS groups) diets for 6 weeks. Mice were assessed for Zn status, serum and urinary indices of diabetes, and gastrocnemius insulin receptor concentration and tyrosine kinase activity. Fasting serum glucose concentrations were significantly lower in the dbZS group compared with the dbZD group (19.3 ± 2.9 and 27.9 ± 4.1 mM, respectively), whereas the dbC mice had an intermediate value. There was a negative correlation between femur Zn and serum glucose concentrations (r = −0.59 for lean mice, P = 0.007). The dbZS group had higher pancreatic Zn and lower circulating insulin concentrations than dbZC mice. Insulin-stimulated tyrosine kinase activity in gastrocnemius muscle was higher in the db/db genotype, and insulin receptor concentration was not altered. In summary, dietary Zn supplementation attenuated hyperglycemia and hyperinsulinemia in db/db mice, suggesting that the roles of Zn in pancreatic function and peripheral tissue glucose uptake need to be further investigated.

The effect of dietary Zn or Cu deficiency on the primary free radical defense system was examined in the lungs and livers of 6-wk-old rats. Enzymatic components (superoxide dismutase, catalase and glutathione peroxidase) and nonenzymatic components (α-tocopherol, ascorbate, glutathione and metallothionein) of the primary free radical defense system, as well as tissue concentrations of Cu, Zn and Fe, were measured. Liver CuZn-superoxide dismutase and liver catalase activities were significantly lower (P < 0.05), and lung metallothionein and liver ascorbate concentrations were significantly higher (P < 0.05) in Cu-deficient rats than in either pair-fed or ad libitum-fed controls. Zn-deficient rats had a significantly lower (P < 0.05) concentration of liver metallothionein than either control group. Other changes in the enzymatic and nonenzymatic components of the primary free radical defense system could be attributed to the reduction in feed intake by Zn- or Cu-deficient rats and not to a direct effect of the Zn or Cu deficiency per se. The primary free radical defense system in lung and liver of severely Zn- or Cudeficient rats was not seriously compromised.