Protective Role of Histidine Supplementation Against Oxidative Stress Damage in the Management of Anemia of Chronic Kidney Disease

Abstract

Anemia is a major health condition associated with chronic kidney disease (CKD). A key underlying cause of this disorder is iron deficiency. Although intravenous iron treatment can be beneficial in correcting CKD-associated anemia, surplus iron can be detrimental and cause complications. Excessive generation of reactive oxygen species (ROS), particularly by mitochondria, leads to tissue oxidation and damage to DNA, proteins, and lipids. Oxidative stress increase in CKD has been further implicated in the pathogenesis of vascular calcification. Iron supplementation leads to the availability of excess free iron that is toxic and generates ROS that is linked, in turn, to inflammation, endothelial dysfunction, and cardiovascular disease. Histidine is indispensable to uremic patients because of the tendency toward negative plasma histidine levels. Histidine-deficient diets predispose healthy subjects to anemia and accentuate anemia in chronic uremic patients. Histidine is essential in globin synthesis and erythropoiesis and has also been implicated in the enhancement of iron absorption from human diets. Studies have found that L-histidine exhibits antioxidant capabilities, such as scavenging free radicals and chelating divalent metal ions, hence the advocacy for its use in improving oxidative stress in CKD. The current review advances and discusses evidence for iron-induced toxicity in CKD and the mechanisms by which histidine exerts cytoprotective functions.

Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement

“…In addition to the supposed positive effect of HIS on erythropoiesis, a reason to advocate HIS supplementation in patients with chronic kidney disease is its potential to neutralize excessive production of ROS and tissue damage associated with iron overload [133]. Combined supplementation of iron with HIS has been shown to be more effective in therapy of uremic anemia when compared with iron alone [129].…”

Cardiac protection of functional chicken‐liver hydrolysates on the high‐fat diet induced cardio‐renal damages via sustaining autophagy homeostasis

“…The intravenous administration of a large number of amino acids protected the renal tubule system where both reabsorption and anion balance are retained within chronic renal disease patients . Moreover, l‐ histidine, l‐ arginine, and l‐ ornithine supplements were protective against oxidative stress damage and inflammation in chronic kidney disease patients, and those amino acids were abundant in CLHs (Table ) …”

“…43 Moreover, L-histidine, L-arginine, and L-ornithine supplements were protective against oxidative stress damage and inflammation in chronic kidney disease patients, and those amino acids were abundant in CLHs (Table 1). [44][45][46] Myocardial fibrosis was a significant contributor and linked obesity, left ventricular dysfunction, and heart failure. 47 Moreover, tissue remodeling and wound healing played a crucial role in injury and fibrosis progression.…”

Fluorimetric Method for the Determination of Histidine in Random Human Urine Based on Zone Fluidics

“…In this way, the calibration curve is more representative including potential day-to-day variations. The following regression Equation (1) was obtained: F = 420.1 (±3.4) [HIS] + 63.1 (±3.9), r 2 = 0.994 (1) where F is the fluorescence intensity as measured by the detector. Linearity was further validated using the back-calculated concentrations (residuals).…”

“…l-Histidine (HIS) is an essential amino-acid that has proven to play unique roles in human organism [1,2]. Representative examples include: (i) when it is co-administered with iron, it helps towards the most rapid increase in its plasma levels in patients with anemia, especially to those with chronic kidney failure [3]; (ii) in vitro studies have demonstrated that due to its metal chelating properties HIS is the most effective hydroxyl radical scavenger compared to several amino acids that were examined [4]; (iii) it has significant anti-inflammatory properties, mainly due to the production on histamine through enzymatic decarboxylation [5]; and (iv) a recent study also revealed impressive improvement of the metabolic syndrome through supplementation with HIS [6,7].…”