Dr. Ron’s Research Review – September 15, 2010

This week’s research review contains a review article on gastric secretion; garlic; antioxidants and pro-oxidants.

Gastric exocrine and endocrine secretion (Schubert 2009)

Acid facilitates the digestion of protein and absorption of iron, calcium, vitamin B12 as well as prevents bacterial overgrowth, enteric infection, and possibly food allergy. The major stimulants of acid secretion are gastrin, histamine, and acetylcholine.

Antioxidants: Molecules, medicines, and myths (Gutteridge and Halliwell 2010)

There is an industry-driven public obsession with antioxidants, which are equated to safe, health-giving molecules to be swallowed as mega-dose supplements or in fortified foods. Sometimes they are good for you, but sometimes they may not be, and pro-oxidants can be better for you in some circumstances.

Garlic: source of the ultimate antioxidants--sulfenic acids (Vaidya, Ingold et al. 2009)

We suggest that the peroxyl-radical-trapping activity of garlic is primarily due to 2-propenesulfenic acid formed by the decomposition of allicin.

In the News

Daily vitamin B could slow Alzheimer's onset, study finds

By the CNN Wire Staff Link

Dr. Ron

PS

The article on antioxidants is interesting because of the last sentence that "pro-oxidants can better for you in some circumstances". You may have guessed it - they mean new drugs. Oxidative burst inducers decrease inflammation and are being developed for arthritis. (Hultqvist, Olofsson et al. 2006)

There’s also an herb (Notopterygium) that has the same mechanism. (Tang, Cheah et al. 2009)


Articles

Gastric exocrine and endocrine secretion

(Schubert 2009) Download

PURPOSE OF REVIEW: This review summarizes the last year's literature regarding the regulation and measurement of gastric exocrine and endocrine secretion. RECENT FINDINGS: Parietal cells, distributed along much of the length of the oxyntic glands, with highest density in the neck and base, secrete HCl as well as transforming growth factor-alpha, amphiregulin, heparin-binding epidermal growth factor-like growth factor, and sonic hedgehog. Acid facilitates the digestion of protein and absorption of iron, calcium, vitamin B(12) as well as prevents bacterial overgrowth, enteric infection, and possibly food allergy. The major stimulants of acid secretion are gastrin, histamine, and acetylcholine. Ghrelin and orexin also stimulate acid secretion. The main inhibitor of acid secretion is somatostatin. Nitric oxide and dopamine also inhibit acid secretion. Although Helicobacter pylori is associated with duodenal ulcer disease, most patients infected with the organism produce less than normal amount of acid. The cytoskeletal proteins ezrin and moesin participate in parietal cell acid and chief cell pepsinogen secretion, respectively. SUMMARY: Despite our vast knowledge, the understanding of the regulation of gastric acid secretion in health and disease is far from complete. A better understanding of the pathways and mechanisms regulating acid secretion should lead to improved management of patients with acid-induced disorders as well as those who secrete too little acid.

Antioxidants: Molecules, medicines, and myths

            (Gutteridge and Halliwell 2010) Download

There is an industry-driven public obsession with antioxidants, which are equated to safe, health-giving molecules to be swallowed as mega-dose supplements or in fortified foods. Sometimes they are good for you, but sometimes they may not be, and pro-oxidants can be better for you in some circumstances. This article re-examines and challenges some basic assumptions in the nutritional antioxidant field.

Garlic: source of the ultimate antioxidants--sulfenic acids

            (Vaidya, Ingold et al. 2009) Download

A new arthritis therapy with oxidative burst inducers

            (Hultqvist, Olofsson et al. 2006) Download

BACKGROUND: Despite recent successes with biological agents as therapy for autoimmune inflammatory diseases such as rheumatoid arthritis (RA), many patients fail to respond adequately to these treatments, making a continued search for new therapies extremely important. Recently, the prevailing hypothesis that reactive oxygen species (ROS) promote inflammation was challenged when polymorphisms in Ncf1, that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. Based on these findings we developed a new therapy for arthritis using oxidative burst-inducing substances. METHODS AND FINDINGS: Treatment of rats with phytol (3,7,11,15-tetramethyl-2-hexadecene-1-ol) increased oxidative burst in vivo and thereby corrected the effect of the genetic polymorphism in arthritis-prone Ncf1(DA) rats. Importantly, phytol treatment also decreased the autoimmune response and ameliorated both the acute and chronic phases of arthritis. When compared to standard therapies for RA, anti-tumour necrosis factor-alpha and methotrexate, phytol showed equally good or better therapeutic properties. Finally, phytol mediated its effect within hours of administration and involved modulation of T cell activation, as injection prevented adoptive transfer of disease with arthritogenic T cells. CONCLUSIONS: Treatment of arthritis with ROS-promoting substances such as phytol targets a newly discovered pathway leading to autoimmune inflammatory disease and introduces a novel class of therapeutics for treatment of RA and possibly other chronic inflammatory diseases.

Notopterygium forbesii Boiss extract and its active constituent phenethyl ferulate attenuate pro-inflammatory responses to lipopolysaccharide in RAW 264.7 macrophages. A "protective" role for oxidative stress?

            (Tang, Cheah et al. 2009)

Oxidative stress and oxidative modification of biomolecules are involved in several physiological and pathophysiological processes. We have previously reported that Notopterygium forbesii Boiss (NF), a traditional Chinese medicine, and its active constituents, including phenethyl ferulate (PF), bergaptol, and isoimperatorin, induced oxidative stress with increased levels of reactive species and heme oxygenase-1 in human fetal hepatocytes. The current study determined the effects of NF and PF on the inflammatory effects of lipopolysaccharide (LPS). Exposure of RAW 264.7 macrophages to LPS increased the expression of inducible nitric oxide synthase and cyclooxygenase 2 and stimulated the formation of reactive nitrogen species. In a coculture system, the LPS-activated macrophages also induced expression of cell adhesion molecules (including E-selectin, intercellular cell adhesion molecule 1, and vascular cell adhesion molecule 1) in human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC). Preincubation of macrophages with NF or PF attenuated the effects of LPS on macrophages as well as their effects on HUVEC and VSMC. These inhibitory effects of NF and PF were decreased in the presence of N-acetyl-l-cysteine (NAC). At the same time, NAC also reduced NF- or PF-induced increases in reactive oxygen species (ROS) and Hsp32 protein levels and the formation of protein carbonyls in the macrophages. These results suggest that NF- or PF-induced ROS generation and oxidative modifications of intracellular proteins may be responsible for the inhibitory actions of NF and PF on LPS-induced inflammatory responses. These data add to the growing literature that ROS may sometimes be anti-inflammatory.


References

Gutteridge, J. M. and B. Halliwell (2010). "Antioxidants: Molecules, medicines, and myths." Biochem Biophys Res Commun 393(4): 561-4.

Hultqvist, M., P. Olofsson, et al. (2006). "A new arthritis therapy with oxidative burst inducers." PLoS Med 3(9): e348.

Schubert, M. L. (2009). "Gastric exocrine and endocrine secretion." Curr Opin Gastroenterol 25(6): 529-36.

Tang, S. Y., I. K. Cheah, et al. (2009). "Notopterygium forbesii Boiss extract and its active constituent phenethyl ferulate attenuate pro-inflammatory responses to lipopolysaccharide in RAW 264.7 macrophages. A "protective" role for oxidative stress?" Chem Res Toxicol 22(8): 1473-82.

Vaidya, V., K. U. Ingold, et al. (2009). "Garlic: source of the ultimate antioxidants--sulfenic acids." Angew Chem Int Ed Engl 48(1): 157-60.