Irina Stoian

Hepcidin – central regulator of iron metabolism

The knowledge about mammalian iron metabolism has advanced dramatically over the past decades. Studies of genetics, biochemistry and molecular biology allowed us the identification and characterization of many of the molecules involved in regulation of iron homeostasis. Important progresses were made after the discovery in 2000 of a small peptide – hepcidin – that has been proved to play a central role in orchestration on iron metabolism also providing a link between iron metabolism and inflammation and innate immunity. Hepcidin directly interacts with ferroportin (FPN), the only known mammalian iron exporter, which is expressed by enterocytes, macrophages and hepatocytes. The direct hepcidin–FPN interaction allows an adaptative response from the body in situations that alter normal iron homeostasis (hypoxia, anemia, iron deficiency, iron overload, and inflammation).

Chelidonium majus – an Integrative Review: Traditional Knowledge versus Modern Findings

Chelidonium majus L. (family Papaveraceae), or greater celandine, is an important plant in western phytotherapy and in traditional Chinese medicine. Crude extracts of C. majus as well as purified compounds derived from it exhibit a broad spectrum of biological activities (antiinflammatory, antimicrobial, antitumoral, analgesic, hepatoprotective) that support some of the traditional uses of C. majus. However, herbal medicine also claims that this plant has several important properties which have not yet been scientifically studied: C. majus is supposed to have diuretic, antitussive and eye-regenerative effects. On the other hand, C. majus also has scientifically proven effects, e.g. anti-osteoporotic activity and radioprotection, which are not mentioned in traditional sources. Moreover, recent controversy about the hepatoprotective versus hepatotoxic effects of Chelidonium majus has renewed the interest of the medical community in this plant. This review is intended to integrate traditional ethno-medical knowledge and modern scientific findings about C. majus in order to promote understanding of its therapeutic actions as well as its toxic potential.

Increase in Total Antioxidant Capacity of Plasma despite High Levels of Oxidative Stress in Uncomplicated Type 2 Diabetes Mellitus

OBJECTIVE: Oxidative stress is implicated in the pathophysiology of diabetes mellitus and its chronic complications. The aim of this study was to evaluate plasma antioxidant status in patients with uncomplicated type 2 diabetes, in order to understand the interactions between its components and the diabetic milieu. METHODS: Plasma samples were collected from 15 patients with type 2 diabetes receiving oral antidiabetic agents and from 18 healthy control subjects without diabetes. Glycosylated haemoglobin was measured as an indicator of blood glucose control. Total and residual antioxidant activities were measured. Lipid peroxides were measured as indicators of plasma oxidative stress. Copper and caeruloplasmin were also assayed as possible pro-oxidants. RESULTS: Antioxidant activities, lipid peroxide level, copper concentration and caeruloplasmin activity were significantly increased in the plasma of patients with diabetes compared with control subjects. CONCLUSIONS: The total antioxidant capacity of plasma was increased, despite high levels of oxidative stress, in patients with uncomplicated type 2 diabetes. Increased levels of copper and caeruloplasmin characterized the diabetic milieu, despite an absence of chronic complications.

Significance of platelet‐activating factor acetylhydrolase in patients with non‐insulin‐dependent (type 2) diabetes mellitus

Background: Non‐insulin dependent diabetes mellitus (NIDDM) represents an independent risk factor for cardiovascular diseases (CVD), being characterized by a continnous low‐grade inflammation and endothelial activation state. Plasma platelet ‐ activating factor ‐ acetylhydrolases (PAF‐AHs) are a subgroup of Ca2+ ‐independent phospholipase A2 family (also known as lipoprotein‐associated phospholipases A2) that hydrolyze and inactivate the lipid mediator platelet‐activating factor (PAF) and/or oxidized phospholipids. This enzyme is considered to play an important role in inflammatory diseases and atherosclerosis. The present study aims to investigate the relations between the levels of PAF‐AH activity and LDL‐cholesterol/HDL‐cholesterol (LDL‐ch/HDL‐ch) ratio in NIDDM patients as compared to controls. Methods: serum PAF‐AH activity was measured in 50 patients with dyslipidemia, in 50 NIDDM patients and in 50 controls (normal lipid and glucose levels). Total cholesterol, LDL‐ch, HDL‐ch, triglyceride and blood glucose were determined in all subjects. Results: All NIDDM patients display hiperlipidemia, with increased LDL‐ch and triglyceride levels. There is a significant correlation between LDL‐ch levels (especially LDL‐ch / HDL‐ch ratio) and PAF‐AH activity in dyslipidemic and NIDDM patients. Conclusion: Diabetic and dyslipidemic patients have an increased plasma PAF‐AH activity correlated with their LDL‐ch levels and mainly with LDL‐ch / HDL‐ch ratio. Plasma PAF‐AH high levels appear to be important as a risk marker for endothelial dysfunction in patients with NIDDM.

Review article: The role of adipose tissue in uraemia‐related insulin resistance

SUMMARY:  Adipose tissue is no longer considered to be an inert tissue of which function is to store fat. It actively secretes a number of biologic active compounds that are involved in the regulation of many processes like food intake, energy expenditure, metabolism homeostasis, immunity and blood pressure homeostasis. General metabolism alteration in patients with chronic kidney disease has a profound impact on biology of adipocytes. Chronic renal failure is a pathological condition, of which two major hallmarks are chronic inflammation and insulin resistance. In uraemic patients, adipose tissue became an important source of molecules that are responsible, at least in part, for the metabolic disturbances seen in these patients. Some of these molecules act as pro‐inflammatory agents contributing to the maintenance and enhancement of the chronic inflammatory response. These pro‐inflammatory molecules, along with other molecules secreted by the adipose tissue, have a central position in the aetiology of uraemia‐associated insulin resistance. In this review, we intend to summarize some aspects of the biology of adipokines in uraemia, with emphasis on the link between these molecules and insulin resistance.

Antioxidant defense capacity in scleroderma patients

Abstract Background: Oxidative stress is associated with scleroderma (systemic sclerosis) and is supposed to favor disease progression by complex effects on the vascular endothelium and on fibroblasts. Methods: Plasma oxidative process marker, thiobarbituric acid-reactive substances, and several markers of antioxidant defense capacity (plasma total antioxidant activity, serum albumin, uric acid and glutathione, superoxide dismutase and catalase) were evaluated by spectrophotometric methods using blood samples collected from 23 scleroderma patients and 21 healthy controls. Results: In scleroderma patients, thiobarbituric acid-reactive substances levels (mmol/L plasma) were significantly elevated (29.3±5.8) compared with healthy controls (16.6±3.1, p<0.001). Total antioxidant activity (mmol Trolox/L) was significantly lower in scleroderma patients than in controls (1.29±0.13 vs. 1.55±0.23, p<0.001), as well as the antioxidant gap (mmol Trolox/L) (0.57±0.18 vs. 0.92±0.22, p<0.001). Superoxide dismutase activity (IU/g hemoglobin) was markedly decreased in patients as compared with controls (395±184 vs. 659±211, p<0.001). Conclusions: Lower plasma total antioxidant activity and plasma antioxidant gap in scleroderma patients show that plasma antioxidant defense is deficient in scleroderma patients. As previous studies on this issue are controversial, the decreased erythrocyte superoxide dismutase activity found in the patients in this study needs further investigation. Clin Chem Lab Med 2008;46:836–41.

Influence of Epoietinum Therapy on the Oxidative Stress in Haemodialysis Patients

Background: The causes of oxidative stress in haemodialysis (HD) patients are still controversial. Beside the uraemic state and dialysis-related factors, adjuvant drug therapies such as epoietinum (rHuEpo) and intravenous iron were involved. Methods: Several parameters related to oxidative stress were assessed by spectrophotometry in stable HD patients, treated for at least 2 months with epoietinum (n = 14; mean dose = 97.7 ± 19.1 U/kg/week) or not (n = 15), none of them on iron therapy, and in 13 controls. Plasma thiobarbituric acid-reactive substances (TBARS) were used as markers of reactive species generation. Erythrocyte and plasma antioxidant systems, reflected by non-protein erythrocyte thiols, and erythrocyte enzyme activities – superoxide dismutase (SOD), glutathione peroxidase, catalase and plasma total thiols, respectively – were also investigated. Results: There were no differences between HD subgroups regarding haemoglobin levels. Plasma TBARS was increased in all HD patients as opposed to controls, irrespective of rHuEpo therapy. In addition, no change in antioxidant status parameters between rHuEpo-treated and -untreated patients was observed. Except for SOD, the other antioxidant indices were higher in all HD patients versus controls. Conclusions: These results suggest that (1) chronic HD patients appear to have simultaneously enhanced reactive species generation and antioxidative systems efficiency, and (2) epoietinum therapy did not change their oxidative status, at least in the absence of concomitant iron supplementation and at similar haemoglobin levels.

Phytomedicine in Joint Disorders

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even though many of them have been proven effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarize the available scientific information on the following joint-friendly medicinal plants, which have been tested in human studies: Arnica montana, Boswellia spp., Curcuma spp., Equisetum arvense, Harpagophytum procumbens, Salix spp., Sesamum indicum, Symphytum officinalis, Zingiber officinalis, Panax notoginseng, and Whitania somnifera.

L-arginine catabolism is driven mainly towards nitric oxide synthesis in the erythrocytes of patients with type 2 diabetes at first clinical onset

Background We investigated the l-arginine (l-Arg)–nitric oxide (NO) metabolic pathway in the erythrocytes (RBCs) and plasma of subjects with type 2 diabetes at first clinical onset. Methods RBCs and plasma were collected from 26 patients with type 2 diabetes at first clinical onset and 19 age-matched non-diabetes subjects as controls. l-Arg content was assayed by capillary electrophoresis. We measured arginase activity and nitrate/nitrite concentrations by spectrophotometry, and glycosylated haemoglobin (HbA1c) by standardized immunoturbidimetry. Results We found that, when compared with controls, l-Arg content was similar in RBCs while decreased in the plasma of patients with type 2 diabetes. Interestingly, arginase activity was lower in RBCs and increased in plasma of patients with diabetes. NO production was higher in RBCs in patients with type 2 diabetes, while no difference was found in the plasma of our subjects. Conclusions l-Arg catabolism is driven mainly towards NO synthesis in RBCs of patients with type 2 diabetes at first clinical onset. The decreased RBC arginase activity could be considered a potential mechanism of increased RBC NO production in early diabetes. Therefore, the RBC pool would represent a potentially compensatory intravascular compartment for endothelial dysfunction in diabetes.

Does Dialysis Modality Influence the Oxidative Stress of Uremic Patients

Background/Aims: Since peritoneal membrane is more compatible and residual renal function better preserved during peritoneal dialysis, we questioned whether the oxidative burden in chronic kidney disease (CKD) is influenced by dialysis modality. Methods: 49 stable CKD patients, 17 on continuous ambulatory peritoneal dialysis (CAPD), 16 on hemodialysis (HD), and 16 non-dialyzed, and 13 healthy subjects were enrolled. Plasma thiobarbituric acid-reactive substances (TBARS; nmol/g protein), serum total antioxidant activity (TAA), total plasma-free thiols (Pt-SH; µmol/g protein), albumin and uric acid were measured by spectrophotometry. Serum residual antioxidant activity (RAA) was calculated. Results: TBARS were higher in HD (78.3 ± 20.3) versus both non-dialyzed (53.1 ± 27.9, p = 0.007) and CAPD groups (58.3 ± 19.8, p = 0.008). Pt-SH was reduced in CKD patients, but showed comparable values between dialysis groups. TAA and RAA were similarly increased in HD and CAPD patients than in the other two groups. Conclusion: Oxidative stress occurs in all CKD patients and worsens as renal function declines. Lipid peroxidation seems more augmented during chronic HD as compared to CAPD, but the plasma antioxidant status did not differ between the investigated dialysis methods. Therefore, dialysis modality appears to influence lipid peroxidation without changing the extracellular antioxidant defense of CKD patients.