022-0222411-2408 Reproductive Health Effects of Toxic and Essential Metals in Men

MINISTRY OF SCIENCE, EDUCATION AND SPORTS OF THE REPUBLIC OF CROATIA (2007-2014)

Principal Investigator: Spomenka Telišman (until 31 December 2007), Alica Pizent (since 1 January 2008)

SUMMARY
Recent evidence has indicated a deterioration in the reproductive health of men in many countries over the past few decades, particularly a decrease in semen quality and an increase in prevalence of prostate cancer, but also great differences between and within some countries. The cause of these phenomena is unknown, although a complex role of environmental and lifestyle factors has been implicated. Lead (Pb) and cadmium (Cd) are toxic metals, pervasive in the human environment and accumulate in the human body over a lifetime. In addition to direct toxicity, they can interfere with the metabolism of several essential metals by reducing their bioavailability in the body, can contribute to oxidative stress (implicated in the pathogenesis of male infertility), and can inhibit DNA repair. Copper (Cu), zinc (Zn) and selenium (Se) are essential elements required for optimum activity of many enzymes, including the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) that are protective against oxidative stress. Particularly Zn and Se are important for male reproductive function and can reduce the toxicity of Pb and Cd. Varicocele belongs to the most important causes of male infertility, although the mechanism behind its adverse action is poorly known. Recent data indicate the association of varicocele with an increase in Cd and a decrease in Zn, and with altered activity of antioxidant enzymes in men. Prostate cancer is the 4th most common cancer in men worldwide, and the most common cancer in men in the USA as well as in Croatia. Recent data show a protective role of relatively high serum Se levels against the risk of prostate cancer in men, whereas chronic exposure to Pb and Cd has been shown to decrease Zn and Se, and cause impaired secretory function or damage of the prostate. The objective of this study is to determine the inter-relationship of the blood levels of Pb and Cd, serum levels of Cu, Zn and Se, activities of SOD and GPx in blood, and age, smoking, and alcohol consumption with respect to clinically defined presence and intensity of varicocele, and of prostate damage, in men with no occupational exposure to metals. The purpose is to provide relevant data concerning the etiology, possible substitutional therapy, and prevention of a further deterioration in the reproductive health in men, as well as to evaluate the contribution of each specific environmental and lifestyle factors. The study is important in view of a considerably lower serum Se level, and somewhat higher blood Pb and Cd levels, in the general population of Croatia than in many other countries.

Anticholinesterase Poisons – Biological Effects Of New Antidotes

The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006)

Principal Investigator: Božica Radić

SUMMARY
A toxic effects of anticholinesterases (organophosphorous compounds (OPs) with highly toxic nervous warfare agents and carbamates) is irreversible inhibition of hydrolytic enzymes: acethylcholinesterase (AChE), the enzyme of vital importance, and buthyrilcholinesterase (BuChE).

The physiological role of AChE is to hydrolyse the neurotransmitter acethylcholine released in the process of cholynergic transmission of nerve impulses. AChE inhibited by OPs and carbamates does not hydrolyse acethylcholine. The consequence is the blocking of nerve impulses in the central and peripheral nervous system. The therapy of anticholinesterase poisoning includes specific drugs, called antidotes (atropine, oximes etc.). As there is no universal therapy for anticholinesterase poisoning, research of new antidotes aims at finding better therapeutic solutions. We are investigating in vitro and in vivo abilities of new potential antidotes: pyridinium compounds and derivatives of tenocyclidine-adamantane. Terrorist activities in the world have shown that chemical warfare agents are the still a threat, and have given new impulse and importance to this type of research.

A part of this project is focused on investigation of the efficiency of new antidotes on inhibited AChE. The physiologic role of BuChE is unknown. Scarce literature data show that BuChE is involved in the metabolism of lipids.

Additionally this project proposes to investigate the effects of BuChE inhibition on changes in the concentrations of  lipids (cholesterol and triglycerides) and lipoproteins (HDL, LDL, IDL) in rat’s plasma, as well as the activity of some enzymes involved in the metabolism of lipoproteins (lipoprotein lipase, lecitin-cholesterol-acyl transferase). The results may have clinical application in the diagnosis of patients with hiperlipidemia. Research will be performed in vitro and in vivo on experimental animals (mice, rats).

022-0222411-2410 Allergotoxic Effects of General and Occupational Environment

MINISTRY OF SCIENCE, EDUCATION AND SPORTS OF THE REPUBLIC OF CROATIA (2007-2014)

Principal Investigator: Jelena Macan

SUMMARY
Key and initial facts:
Allergotoxicology studies include parallel research of environmental pollutants and the development of allergic reactions in humans. Climatic changes, development of industrial technology and modern life style resulted in the evolution of new common and occupational allergens and other contaminants.
Our former studies have shown that the population of the Mediterranean region in Croatia is exposed to the significantly higher levels of mite allergens than in the continental region, which is not in accordance with the expected proportional difference in the number of sensitized individuals.
Goals and hypothesis:
Aim of the study is to determine regional specificity of environmental and life style risk factors, and to identify new risks for the development of sensitization in adult population in continental and Mediterranean region of Croatia. Hypotesis is that environmental as well as life style factors may cause the differences in the frequency of sensitization markers and allergic respiratory and skin diseases in adult population between these two regions. Within the same region, risk of sensitization to mites should be higher in persons exposed to mites concurrently in environmental and occupational conditions in comparison to persons without occupational exposure.
Expected results:
The effects of environmental factors on the development of allergic disorders will be determined in the adult population of the continental and Mediterranean region of Croatia. Previously detected differences in the frequency of sensitization to mite allergens in adult population between the two regions will be clarified. The significance of sensitization to common allergens for the development of occupationally induced allergic disorders will be estimated.
Verification of results:
Data and biological samples will be collected and analysed by means of standardized or validated procedures and methods that enable verification of results.
Importance of results:
The study contributes to the clarification of ethiopathogenesis of common and occupational allergic disorders. The results may be used for planning and implementation of intervention studies, preventive public health actions and for the improvement of diagnostic and therapeutic procedures. In collaboration with industry, the results will be applied in generating technological processes and products safer in view of health protection.