Concentrations of Transition Metal Ions in Rat Lungs after Tobacco Smoke Exposure and Treatment with His-Leu Dipeptide

Abstract

Tobacco smoking is deleterious to the lungs because it exposes them to many toxic substances. These include transition metal ions, such as cadmium. However, there is a lack of information about the influence of endogenous metal-binding peptides, such as His-Leu (HL), on the lung distribution of transition metals in smokers. To address this, we administered HL subcutaneously to rats exposed to tobacco smoke for six weeks, then we measured the concentrations of transition metal ions in the lungs. We found that exposure to tobacco smoke elevates the concentrations of Cd(II) and Cu(II). Administration of the HL peptide, whose elevation is a consequence of angiotensin receptor blocker anti-hypertension therapy, increases the concentration of Fe in the lungs of rats exposed to smoke. These findings suggest that smoking is a risk factor for patients receiving angiotensin receptor blockers to treat hypertension.

The Angiotensin Metabolite His-Leu Is a Strong Copper Chelator Forming Highly Redox Active Species

“…Such a His-Leu level is hypothetically possible in the lungs and kidneys that are the primary sites of its production and also in the course of antihypertension therapies using blockers of angiotensin receptors. Such therapy leads to A2 accumulation , and can possibly elevate His-Leu as the accompanying A1 metabolite . Furthermore, the LMW pool probably comprises ternary complexes, and His-Leu can be a good candidate for such, on the basis of its readiness to form bis-complexes.…”

“…Such therapy leads to A2 accumulation 83 , 84 and can possibly elevate His-Leu as the accompanying A1 metabolite. 46 Furthermore, the LMW pool probably comprises ternary complexes, 78 and His-Leu can be a good candidate for such, on the basis of its readiness to form bis-complexes. Moreover, the kinetic characteristics should also be in favor of His-Leu.…”

“…Such therapy leads to A2 accumulation 83,84 and can possibly elevate His-Leu as the accompanying A1 metabolite. 46 Furthermore, the LMW pool probably comprises ternary complexes, 78 and His-Leu can be a good candidate for such, on the basis of its readiness to form bis- 36 His-Lys, 43 HVGD, 76,77 GHK, 23 GGH, 19 histidine (His), 78 and histamine (Hstm)] 79 His] copper pools, using the literature binding constants. 19,23,78 The shaded field corresponds to the possible His-Leu concentration range in the bloodstream in general (darker) and in kidney circulation (lighter).…”

“…A recent study investigated the physiological effects of His-Leu in rats. 46 No direct association was found between His-Leu administration and metal ion (including copper) distribution in lung tissue. However, the levels of A2 precursors in humans are generally 10-fold higher than in rodents.…”

“…A recent study investigated the physiological effects of His-Leu in rats . No direct association was found between His-Leu administration and metal ion (including copper) distribution in lung tissue.…”