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World J Nephrol. Nov 6, 2013; 2(4): 111-124
Published online Nov 6, 2013. doi: 10.5527/wjn.v2.i4.111
Vitamin E and diabetic nephropathy in mice model and humans
Nakhoul Farid, Dahan Inbal, Nakhoul Nakhoul, Farber Evgeny, Rachel Miller-Lotan, Andrew P Levy, Asleh Rabea
Nakhoul Farid, Dahan Inbal, Farber Evgeny, Department of Nephrology and Hypertension, Baruch-Padeh Poriya Medical Center, Faculty of Medicine, Bar-Ilan University, Lower Galilee 15208, Israel
Nakhoul Nakhoul, Ophtalmology Unit, Baruch-Padeh Poriya Medical Center, Lower Galilee 15208, Israel
Rachel Miller-Lotan, Andrew P Levy, Asleh Rabea, The Vascular Biology Lab, the Technion Faculty of Medicine, Haifa 31096, Israel
Author contributions: Farid N, Nakhoul N, Miller-Lotan R designed research; Farid N, Inbal D and Rabea A performed research; Miller-Lotan R contributed new reagents or analytic tools; Evgeny F, Farid N and Levy AP analyzed data; Farid N and Nakhoul N wrote the paper.
Correspondence to: Nakhoul Farid, MD, Department of Nephrology and Hypertension, Baruch-Padeh Poriya Medical Center, Faculty of Medicine, Bar Ilan University Galilee, Max ve-Anna Webb, Ramat Gan, Lower Galilee 15208, Israel. fnakhoul@poria.health.gov.il
Telephone: +97-24-6652587 Fax: +97-24-6652587
Received: May 15, 2013
Revised: June 11, 2013
Accepted: October 18, 2013
Published online: November 6, 2013
Processing time: 172 Days and 22.2 Hours
Abstract

Diabetes mellitus (DM) is associated with increased oxidative stress due to elevated glucose levels in the plasma. Glucose promotes glycosylation of both plasma and cellular proteins with increased risk for vascular events. Diabetic patients suffer from a higher incidence of cardiovascular complications such as diabetic nephropathy. Haptoglobin (Hp) is an antioxidant plasma protein which binds free hemoglobin, thus preventing heme-iron mediated oxidation. Two alleles exist at the Hp gene locus (1 and 2) encoding three possible Hp genotypes that differ in their antioxidant ability, and may respond differently to vitamin E treatment. Several clinical studies to have shown that Hp 1-1 genotype is a superior antioxidant to the Hp 2-2 genotype and Hp 2-2 genotype is associated with a higher incidence of cardiovascular disease. Vitamin E was found to have beneficial effect in patient and mice with Hp 2-2 genotype. In this review we have summarized the results of our studies in patients with diabetic nephropathy treated with vitamin E and in diabetic mice with different haptoglobin genotypes.

Keywords: Haptoglobin; Cardio-vascular complications; Diabetic nephropathy; Vitamin E

Core tip: In diabetes mellitus there is an increase in oxygen radical formation due to glucose auto oxidation, the formation of advanced glycosylation end products, and metabolic stress. Epidemiologic studies suggest that vitamin E supplementation might decrease the risk of developing cardiovascular disease, others showed increased risk of cardiac death with the vitamin E treatment. To the contradictory results in the literature regarding the beneficial role of vitamin E in protecting against cardiovascular complications, high dose vitamin E supplementation has not been recommended by the medical community. In fact, a meta-analysis of over 135000 individuals treated with vitamin E concluded that high dose vitamin E (greater than 400 mg/d) slightly increases the risk of mortality. However, recent investigations into the polymorphic serum protein haptoglobin (Hp) indicate that vitamin E may be beneficial in a genetically defined subgroup of patients, namely, diabetic patients of the Hp 2-2 genotype. The role of Hp as an antioxidant, its importance in diabetes, and the therapeutic role of vitamin E will be discussed in this review.