Vitamin C supplementation does not protect L‐gulono‐γ‐lactone oxidase‐deficient mice from Helicobacter pylori‐induced gastritis and gastric premalignancy

Abstract

In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C‐deficient B6.129P2‐Gulotm1Umc/mmcd (gulo−/−) mice lacking L‐gulono‐γ‐lactone oxidase, we compared gastric lesions and Th1 immune responses in H. pylori‐infected gulo−/− mice supplemented with low (33 mg/L) or high (3,300 mg/L) vitamin C in drinking water for 16 or 32 weeks. Vitamin C levels in plasma and gastric tissue correlated with the vitamin C supplementation levels in gulo−/− mice. H. pylori infection resulted in comparable gastritis and premalignant lesions in wildtype C57BL/6 and gulo−/− mice supplemented with high vitamin C, but lesions were less severe in gulo−/− mice supplemented with low vitamin C at 32 weeks post infection. The reduced gastric lesions in infected gulo−/− mice supplemented with low vitamin C correlated with reduced Th1‐associated IgG2c, gastric IFN‐γ and TNF‐α mRNA and higher H. pylori colonization levels. These results in the H. pylori‐infected gulo−/− mouse model suggest that although supplementation with a high level of vitamin C achieved physiologically normal vitamin C levels in plasma and gastric tissue, this dose of vitamin C did not protect gulo−/− mice from H. pylori‐induced premalignant gastric lesions. In addition, less severe gastric lesions in H.pylori infected gulo−/− mice supplemented with low vitamin C correlated with an attenuated Th1 inflammatory response. © 2007 Wiley‐Liss, Inc.

Concurrent supplementation of arginine and antioxidant vitamins E and C reduces oxidative stress in broiler chickens after a challenge withEimeriaspp.

“…Availability of NO refers to a higher synthesis of NO by NO-synthase (NOS) and to reductions in superoxide generated from the oxygenase domain of NOS due to ''NOS uncoupling'' (Park et al 2015). Lee et al (2008) reported that VC has the ability to stimulate interferon-g activity by increasing the amount of interferon mRNA, hence increasing the microbicidal ability of interferon-g through the NADPH oxidase system, up-regulating NO production, tryptophan depletion and up-regulating lysosomal enzymes promoting microbe destruction (Pfefferkorn 1984;Drapier et al 1988; Fig. 1.…”

Ascorbate promotes carbon tetrachloride-induced hepatic injury in senescence marker protein 30-deficient mice by enhancing inflammation

“…An animal study by Victor et al [40] has shown that macrophages and lymphocytes need an appropriate level of antioxidants, such as ascorbic acid, under oxidative stress conditions. More interestingly, the studies by Lee et al [41] revealed that Helicobacter pylori infections resulted in comparable gastritis and premalignant lesions in WT mice and Gulo −/− mice (ascorbate deficient mice) fed high dose of ascorbate, but the lesions were less severe in Gulo −/− mice fed low-doses of ascorbate; in contrast, less severe lesions of H.pylori infected Gulo −/− mice correlated with reduced Th1-associated IgG2 and higher H.pylori colonization levels. We also confirmed mild liver injury with higher H.pylori colonization levels in CCl 4 plus H. pylori-treated SMP30 −/− mice whereas ascorbate supplementation caused more severe liver injury with lower colonization levels in CCl 4 plus H. pylori-treated SMP30 −/− mice [our unpublished data].…”

Long-Term Intake of High Doses of Vitamin C Down-regulates Anti-oxidant Enzymes in Human Erythrocytes

“…Vitamin C has been tested on various ROS-associated diseases such as motor dysfunction by cerebral ischemia (28), lung cancer risk (29), H. pylori-induced gastritis and gastric carcinoma (30), and degenerative osteoarthritis (31), but the results were negative. One of the reasons for the negative effects may be this limitation in the anti-oxidant capacity.…”

“…Vitamin C is one of the anti-oxidants that have been used most frequently for this purpose. However, the results appear to be inconsistent as some studies report beneficial effects (9) and some show negative effects (10). Some reports even warn that vitamin can be detrimental since it can act as a pro-oxidant (11).…”