Interaction Between the Haptoglobin Genotype and Vitamin E on Cardiovascular Disease in Diabetes

Hochberg I, Berinstein EM, Milman U, Shapira C, Levy AP

Curr Diab Rep. 2017 Jun;17(6):42. doi: 10.1007/s11892-017-0868-1.

Abstract

PURPOSE OF REVIEW:

Despite compelling evidence regarding the importance of oxidant stress in the development of vascular complications and observational studies suggesting that vitamin E may be protective from these complications, multiple clinical trials have failed to show benefit from vitamin E supplementation in the prevention of vascular complications in diabetes. One possible explanation for this failure of vitamin E may have been inappropriate patient selection. This review seeks to provide the clinical evidence and mechanistic basis for why a subset of individuals defined by their haptoglobin (Hp) genotype may derive cardiovascular protection by vitamin E supplementation.

RECENT FINDINGS:

Clinical trial data from the HOPE, ICARE, and WHS studies is presented showing a pharmacogenomic interaction between the Hp genotype and vitamin E on the development of CVD. Specifically, in individuals with diabetes and the Hp2-2 genotype, vitamin E has been shown to be associated with an approximately 35% reduction in CVD. Cardioprotection by vitamin E in individuals with the Hp2-2 genotype appears to be mediated in part by an improvement in HDL functionality as demonstrated in three independent trials in both type 1 diabetes and type 2 diabetes. Vitamin E may provide benefit in reducing CVD in Hp2-2 individuals with diabetes. However, in order for this pharmacogenomic algorithm to be accepted as a standard of care and used clinically, an additional large prospective study will need to be performed.

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Protective effects of Vitamin E on CCl4-induced testicular toxicity in male rats.

El-Faras AA, Sadek IA, Ali YE, Khalil M, Mussa EB.

Physiol Int. 2016 Jun 1;103(2):157-168. doi: 10.1556/036.103.2016.2.3.

Abstract

The increased generation of free radicals plays an important role in testicular damage. The present study aimed to investigate the adverse effects of carbon tetrachloride (CCl4) on the reproductive system of male rats as well as to examine whether Vitamin E (VE) is able to ameliorate these effects. The rats were equally divided into three groups: control, CCl4-treated, and CCl4 + VE-treated groups. After 4 weeks of treatment, the decrease in body and testes weights, sperm parameters, and the decrease in serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone of CCl4-treated rats were ameliorated by VE treatment. The co-administration of VE with CCl4significantly decreased the level of lipid peroxidation production (malondialdehyde) and increased the activity of anti-oxidant enzymes (superoxide dismutase and catalase) when compared with the CCl4 group. Moreover, VE prevented CCl4-induced severe testicular histopathological lesions and deformities in spermatogenesis. The results demonstrate that VE augments the anti-oxidants’ defense mechanism against CCl4-induced reproductive toxicity suggesting a therapeutic role in free radical-mediated infertility.

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Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice.

Hayashi D, Yagi K, Song C, Ueda S, Yamanoue M, Topham M, Suzaki T, Saito N, Emoto N, Shirai Y.

Sci Rep. 2017 Jun 1;7(1):2597. doi: 10.1038/s41598-017-02354-3.

Abstract

Diabetic nephropathy (DN) is one of vascular complications of diabetes and is caused by abnormal protein kinase C activation as a result of increased diacylglycerol (DG) production in diabetic hyperglycaemia. Diacylglycerol kinase (DGK) converts DG into phosphatidic acid. Therefore, it is expected that the activation of DGK would ameliorate DN. Indeed, it has been reported that vitamin E (VtE) ameliorates DN in rat by activating DGK, and we recently reported that VtE specifically activates DGKα isoform in vitro. However, whether DGKα is involved in the VtE-induced amelioration of DN in vivo remains unknown. Therefore, we investigated the VtE-induced amelioration of DN in wild-type (DGKα+/+) and DGKα-deficient (DGKα-/-) mice in which diabetes was induced by streptozocin. Several symptoms of DN were ameliorated by VtE treatment in the DGKα+/+ mice but not in the DGKα-/- mice. Moreover, transmission electron microscopy of glomeruli and immunofluorescent staining of glomerular epithelial cells (podocytes) indicated that VtE ameliorates podocyte pathology and prevents podocyte loss in the DGKα+/+ mice but not in the DGKα-/- mice. We showed that VtE can ameliorate DN in mice and that DGKα is involved in the VtE-induced amelioration of DN in vivo, suggesting that DGKα is an attractive therapeutic target for DN.

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