Faik Atroshi

Association of cadmium with human breast cancer

The carcinogenic potential of cadmium might be affected by several factors such as smoking, hormones and presence of other metals, such as selenium and zinc. Cadmium was analyzed in breast-fat tissue of 43 breast cancer patients and 32 healthy control subjects. Patients were thoroughly characterized according to such variables as stage of cancer, smoking habits, and number of children. Correlation of cadmium levels with these variables, with hormone receptors, and with previously reported selenium and zinc were all analyzed. The mean cadmium concentration found in breast cancer patients (20.4 +/- 17.5 micrograms/g) did not differ significantly from that of the healthy controls (31.7 +/- 39.4 micrograms/g). However, unexpectedly high concentrations of cadmium (3.2-86.9 vs. 0.1-160.4 micrograms/g) were found in breast samples, which may indicate that cadmium binding proteins exist in human breast tissue. Correlation of cadmium with smoking rate of cancer patients was positive (Rs = 0.0505, p < 0.05). Correlation of cadmium with estrogen receptors in breast cancer was suggestive (Rs = 0.309, 28 cases, P = 0.06). No correlation was found with other trace elements such as selenium, zinc and copper. These results seem neither to prove nor to disprove the role of cadmium in breast cancer initiation, promotion or progression.

RETRACTED: Antioxidant nutrients and mycotoxins

This article has been retracted at the request of the editor. Reason: This article contained extensive text that originally appeared in the Journal of Food Protection (FABIO GALVANO, ANDREA PIVA, ALBERTO RITIENI, and GIACOMO GALVANO published by the International Association for Food Protection. Dietary Strategies to Counteract the Effects of Mycotoxins: A Review. J. Food Prot. (2001) Vol. 64 (1): 120–131). Toxicology publishes only original work, and on the occasion when brief excerpts or quotes from other sources are used, this must be clearly indicated with full acknowledgement and written permission from the copyright holder.

T-2 toxin-induced DNA damage in mouse livers: The effect of pretreatment with coenzyme Q10 and α-tocopherol

Active oxygen species are reported to cause organ damage. This study was therefore designed to determine whether oxidative stress contributed to the initiation or progression of hepatic DNA damage produced by T-2 toxin. The aim of the study was also to investigate the behaviour of the antioxidants coenzyme Q10 (CoQ10), and alpha-tocopherol (vitamin E) against DNA damage in the livers of mice fed T-2 toxin. Treatment of fasted mice with a single dose of T-2 toxin (1.8 or 2.8 mg/kg body weight) by oral gavage led to 76% hepatic DNA fragmentation. T-2 toxin also decreased hepatic glutathione (GSH) levels markedly. Pretreatment with CoQ10 (6 mg/kg) together with alpha tocopherol (6 mg/kg) decreased DNA damage. The CoQ10 and vitamin E showed some protection against toxic cell death and glutathione depletion caused by T-2 toxin. Oxidative damage caused by T-2 toxin may be one of the underlying mechanisms for T-2 toxin-induced cell injury and DNA damage, which eventually lead to tumourigenesis.

Increase in non-transferrin bound iron and the oxidative stress status in epilepsy patients treated using valproic acid monotherapy.

OBJECTIVE This study aims to investigate the alteration of iron homeostasis and oxidative stress status in epilepsy patients treated with valproic acid (VPA) monotherapy. MATERIALS 24 epilepsy patients receiving VPA monotherapy (12 men, 12 women, age 27.5 ± 7.2 y) and 24 sex- and age-matched healthy volunteers were included in the study. METHODS The level of iron status parameters; serum iron, ferritin, transferrin saturation, non-transferrin bound iron (NTBI), serum level of trace elements (copper, zinc and selenium), concentration of antioxidant parameters, activities of antioxidant enzymes and level of lipid peroxidation product were determined. RESULTS NTBI was found in the patients although their other iron status parameters were normal. Levels of antioxidant parameters were decreased while activities of antioxidant enzymes were increased. Levels of serum MDA were significantly increased in patients with epilepsy. The daily dose of valproic acid associated was statistically significant: serum concentration of NTBI (r = 0.579; p = 0.003) and MDA (r = 0.465; p = 0.022). A positive correlation existed between NTBI and zinc (r = 0.522; p = 0.009). CONCLUSION According to our results, VPA treatment in patients with epilepsy contributes to the metabolism of iron, leading to the formation of NTBI and an increase in oxidative stress.

Characterization of hemolytic activity of Staphylococcus aureus strains isolated from bovine mastitic milk

Beta (beta) and delta (delta)-hemolysin of Staphylococcus aureus strains were cultured in vitro in milk lactoserum (whey) prepared from both healthy and mastitis bovine milk. Production of beta- and delta-hemolysins were detected in 12 out of 50 strains studied. The association between N-acetyl-beta-D-glucosaminidase (NAGase) activity, plasmin activity (PL) and trypsin inhibitory capacity (TIC), known as inflammatory indicators for mastitis, and hemolytic activity were also studied. Mastitic milk decreased directly the lytic effect of both beta-and delta-hemolysins of S. aureus on hemolytical blood agar plates. S. aureus in healthy milk samples produced more beta-hemolysin (3 times) and delta-hemolysin (2 times) when compared to S. aureus supernatants in milk from infected quarters. Furthermore, beta- and delta-hemolysis correlated negatively with TIC and NAGase and PL activities. Addition of reduced glutathione (GSH) or beta-mercaptoethanol into the artificial medium enhanced hemolysins activity.

Prostaglandins, glutathione metabolism, and lipid peroxidation in relation to inflammation in bovine mastitis.

Bovine mastitis is an infectious disease causing inflammatory changes in the udder. Infection, inflammation and tissue injury are usually associated with lipid peroxidation and the formation of free radicals. We have studied the possible roles of some local tissue factors in mastitis. Among these, prostaglandins (PGs) are typical mediators of inflammation. The metabolism of glutathione (GSH) is in many ways involved in tissue protection particularly in limitation of excessive lipid peroxidation. GSH and GSH-enzymes like GSH-peroxidase (GSH-Px) are also closely involved in the metabolism of arachidonic acid to prostaglandins and other biologically active lipids.

Evaluation of the possible role of coenzyme Q10 and vitamin E in juvenile neuronal ceroid-lipofuscinosis (JNCL)

The juvenile type of neuronal ceroid lipofuscinosis (JNCL) is a recessively inherited, progressive neurodegenerative disease. In this study the levels of the antioxidant factors coenzyme Q10 (CoQ10) and vitamin E (alpha-tocopherol) were measured in plasma samples of 29 JNCL patients and compared to 48 healthy controls. A significant reduction of the coenzyme Q10 level (0.59 +/- 0.25 microgram/ml) was observed in JNCL patients when compared to control subjects (0.80 +/- 0.26 microgram/ml). The level of vitamin E was also reduced markedly in JNCL patients when compared to controls (10.4 +/- 4.1 and 12.1 +/- 4.5 micrograms/ml, respectively). The low levels of CoQ10 and vitamin E in JNCL patients may indicate an impaired antioxidant protection in this disease.

Glutathione Level in Mice Brain After Testosterone Administration

Glutathione (GSH), an SH containing tripeptide, is a powerful antioxidant protecting against free radical damage (Meister and Anderson, 1983). Glutathione has a role in the inactivation of a number of drugs and in the metabolic processing of certain endogenous compounds, such as estrogen, prostaglandins and leukotrienes. Such inhibitors and other compounds that increase GSH synthesis, make it possible to effectively manipulate the metabolism of this compound. GSH is also a coenzyme for several enzymes (Meister, 1984). Since GSH serves effectively in the detoxication of many drugs, the GSH status of an animal is of importance in protection against toxicity. Munthe et.al. (1981) reported that the erythrocyte GSH level increased in RA (Rheumatoid Arthritis) patients receiving “2nd line drugs”. This increase is suggested to precede clinical improvement, and is thus potentially a unique biochemical parameter for monitoring therapy. Recently, Igarashi et.al. (1984) reported that hepatic glutathione S-transferase activity is enhanced significantly in rats after testosterone administration. Since little information is available concerning the behaviour of GSH in the mouse brain after testosterone administration, we examined this effect.

Oxidative Stress and Dietary Interventions in Autism: Exploring the Role of Zinc, Antioxidant Enzymes and Other Micronutrients in the Neurobiology of Autism

Autism Spectrum Disorders (ASD) consist of a set of complex neurodevelopmental disorders characterised by impaired communication and social behaviour, and repetitive or stereotyped pattern of behaviour. The prevalence of ASD has increased in recent decades to 0.6-1% [1-3]. Broadening of the diagnostic criteria and increased awareness of autism among parents and health professionals likely contribute to the prevalence increase. However, the reason for the increase is not completely understood. Alterations of developmental processes and gene expression profiles have been identified in ASD but neuronal mechanisms and perturbations of neuronal networks underlying the ASD phenotype are unclear. ASD varies in severity and the clinical phenotype reflects multifactorial background [4]. Co-morbidity with some genetic syndromes and autism exist [5]. Affected males outnumber females roughly 4:1 [6-8]. The family studies imply that the autism has a strong genetic basis but no single high risk genes for ASD are identified [9]. Hundreds of de novo mutations with extreme locus heterogeneity have been identified in genes encoding protein network ranked for autism candidate genes [10]. Recent studies suggest that environmental factors could play a much larger role in susceptibility to ASD than earlier expected [4]. Since the population’s genetic inheritance is relatively constant over longer periods, the increased incidence rate of autism during last decades could indicate that there is an important environmental component in the etiology of autism [11].

The Role of Prooxidant—Antioxidant Imbalances in the Pathogenesis of Rheumatoid Arthritis

Free oxygen radicals seem to be involved in the pathogenesis of a variety of diseases including rheumatoid arthritis (RA)1. RA is primarily an autoimmune disorder where the cell mediated chronic inflammation is localized in the synovium. Free radicals are suggested to contribute to the initiation and progress of this autoimmune disease. During inflammation neutrophils and macrophages generate reduced oxygen intermediates such as Superoxide radical and hydrogen peroxide. If traces of iron catalyst are present, these species can interact to form highly reactive hydroxyl-radical. Several studies using bleomycin-iron assay have shown that suitable iron catalysts for OH formation are present in synovial fluid taken from patients with rheumatoid arthritis. Therefore it is likely that OH is formed in vivo, and this may account for the degeneration of hyaluronic acid and cartilage observed in joints of rheumatoid patients2.