SERUM HYDROCAPTEUR LONGIDERM

The SERUM HYDROCAPTEUR of LONGIDERM is based on science. One of the major players in the serum is the NDGA. This why I will spend a whole page on its function.

Nordihydroguaiaretic acid (NDGA) is a potent antioxidant compoundand LOX inhibitor found in the long-lived creosote bush. It is believed that NDGA reduces cell damage by free radicals, so under the free-radical theory of aging, could be responsible for the bush's long life.

Lipoxygenases (LOX) belong to a heterogenous family of lipid-peroxidizing enzymes and are involved in the biosynthesis of mediators of inflammation. Based on their regiospecificity during interaction with substrates, LOX have been classified as 5-, 8-, 12-, and 15-LOX. They insert oxygen at carbon 5, 8, 12 or 15 of arachidonic acid, forming 5S-, 8S-, 12S-, or 15S-hydroperoxyeicosatetraenoic acid (5-, 8-, 12-, or 15-HPETE). HPETEs can be further reduced by glutathione peroxidase to the hydroxy forms (5-, 8-, 12-, 15-HETE), respectively. 5-LOX is a dioxygenase that catalyzes the incorporation of molecular oxygen into arachidonic acid (oxygenase activity), producing HPETE and then forms the unstable epoxide LTA4 (LTA4 synthase activity). This is followed by the insertion of molecular oxygen at position C5, converting LTA4 to either 5(S)-hydroxy-6-trans-8, 11, 14-cis-eicosatetranoic acid (5-HETE) or leukotrienes. Hydrolytic attack of LTA4 by leukotriene A4 hydrolase yields LTB4, a potent neutrophil chemoattractant and stimulator of leukocyte adhesion to endothelial cells. LTA4 can be conjugated with glutathione to form LTC4 by the action of LTC4 synthase. 5-LOX pathway has been implicated in the development and progression of human cancers. Hence, 5-LOX inhibitors have been sought for their chemopreventive effects. Inhibition of 5-LOX activity is shown to block prostate cancer cell proliferation. 12-LOX exists in three distinct forms: the leukocyte-type, the platelet-type, and the epidermal form. The platelettype 12-LOX converts arachidonic acid to 12-(S)-HETE. The leukocyte-type 12-LOX metabolizes arachidonic acid or linoleic acid to either 12(S)-HETE or 15(S)-HETE. The epidermal form of 12-LOX converts arachidonic acid to 12-HETE and 15-HETE. 12-LOX has been shown to be involved in both cancer cell proliferation and survival. Inhibition of 12-LOX blocks cell proliferation and induces apoptosis in carcinosarcoma cells. 8-LOX is expressed in the skin after irritation or treatment with tumor promoters. Compared with other LOX enzymes, 8-LOX has received little attention for its role in carcinogenesis and cancer growth. 15-LOX exists as two isozymes, 15-LOX-1 and 15-LOX-2. It converts arachidonic acid to 15-HPETE which is then reduced by glutathione peroxidase to 15-HETE. The preferred substrate for 15-LOX-1 and 15-LOX-2 are linoleic acid and arachidonic acid, respectively. The 15- LOX-1 product, 13-S-HODE, is reported to enhance cell proliferation and potentiate the mitogenic response to EGF in different cell types. 

For these reasons NDGA could play an important role in the prevention of skin cancer. This theory was confirmed by Pupe et al. UVB irradiation on keratinocytes induced induced tumor necrosis factor and this can be induced by reactive oxygen species. NDGA could inhibit the formation of TNF - alpha. The importance of LOX products in the oxdative metabolism is illustrated in the article. NDGA plays a protective effect in the UVB damage. It inhibits the UVB induced TNF mRNA expression.

An important article about the subject on UVB and ROS you find the abstract below. It was published in Photochemistry and Photobiology, 2003, 78(1): 68–74

Induction of Tumor Necrosis Factor–a by UVB:A Role for Reactive Oxygen Intermediates and Eicosanoids

Annemie Pupe, Hugo Degreef and Marjan Garmyn

Department of Dermatology, Katholieke Universiteit Leuven, Leuven, Belgium

ABSTRACT

UVB irradiation induces nuclear factor–jB (NF-jB) activation, tumor necrosis factor–a (TNF-a) expression and reactive oxygen intermediates (ROI) in keratinocytes. We investigated whether ROI play a role in UVB-induced TNF-a mRNA expression. The antioxidants N-acetyl cysteine, NAC, epigallocathin gallate, EGCG, butylated hydroxyanisole (BHA) and vitamin C could reduce UVB-induced TNF-a mRNA levels to various degrees; vitamin E (a-tocopherol) had no effect. BHA was the most potent inhibitor. The oxidant tertiary butylated hydroperoxide could effectively induce TNF-a mRNA expression.

Nordihydroguaiaretic acid (NDGA) and MK-886, inhibitors of lipoxygenase (LOX), and indometacin and quinacrine, inhibitors of cyclooxygenase (COX) and phospholipase A2, respectively, could also reduce UVB-induced TNF-a mRNA expression. Inhibition by NDGA was in concordance with the results for BHA. NDGA, indometacin, quinacrine and BHA could also effectively inhibit the inhibitor of NF-jB degradation, thereby maintaining NF-jB inactivity. In conclusion, we show that ROI are implicated in the induction of TNF-a mRNA by UVB and that not all antioxidants are equally effective inhibitors. COX products and more importantly LOX products, which themselves are products of an oxidative metabolism, are the main ROI implicated in this induction of TNF-a expression by UVB probably via activation of NF-jB.