A Systematic Review of the Antimony Content of the Normal Human Prostate Gland

The prostate gland is subject to various disorders. The etiology and pathogenesis of these diseases remain not well understood. Moreover, despite technological advancements, the differential diagnosis of prostate disorders has become progressively more complex and controversial. It was suggested that the antimony (Sb) level in prostatic tissue plays an important role in prostatic carcinogenesis and its measurement may be useful as a cancer biomarker. These suggestions promoted more detailed studies of the Sb content in the prostatic tissue of healthy subjects. The present study evaluated by systematic analysis the published data for Sb content analyzed in prostatic tissue of “normal” glands. This evaluation reviewed 1998 studies, all of which were published in the years from 1921 to 2020 and were located by searching the databases PubMed, Scopus, ELSEVIER-EMBASE, Cochrane Library, and the Web of Science. The articles were analyzed and “Median of Means” and “Range of Means” were used to examine heterogeneity of the measured Sb content in prostates of apparently healthy men. The objective analysis was performed on data from the 23 studies, which included 1173 subjects. It was found that the range of means of prostatic Sb content reported in the literature for “normal” gland varies widely from 0.0066 mg/kg to 0.071 mg/kg with median of means 0.0085 mg/kg on a wet mass basis. Because of small sample size and high data heterogeneity, we recommend other primary studies be performed. DOI : 10.14302/issn.2470-0436.jos-17-1825 Corresponding Author: Vladimir Zaichick, Radionuclide Diagnostics Department, Medical Radiological Research Centre, Korolyev St. 4, Obninsk 249036, Kaluga region, Russia. E-mail: vzaichick@gmail.com

. In this context, for example, low dose of Sb has some useful effects on health, but significant exposure to this metalloid may result in adverse health effects in different organs or tissues, including malignancy such as Non-Hodgkin's lymphoma and melanoma, cancer of the lung, colon, rectum, bladder, thyroid, pleura, testis and PCa [31][32][33][34].
However, it still remains unclear what precise mechanism is responsible for Sb genotoxicity [30,39].
By now, a few studies have reported the Sb content in tissue of "normal" and affected glands.
However, further investigation has been considered necessary to provide a practical reference data of Sb levels in prostate norm and disorders, because the findings of various studies indicate some discrepancies.
The present study addresses the significance of Sb levels in prostatic tissue as a biomarker of the gland's condition. Therefore, we systematically reviewed all the available relevant literature and performed a statistical analysis of Sb content in tissue of "normal" glands, which may provide valuable insight into the etiology and diagnosis of prostate disorders.

Data Sources and Search Strategy
Aiming at finding the most relevant articles for this review, a thorough comprehensive web search was conducted by consulting the PubMed, Scopus,

Data Extraction
A standard extraction of data was applied, and the following available variables were extracted from each paper: method of Sb determination, number and ages of healthy persons, sample preparation, mean and median of Sb levels, standard deviations of mean, and range of Sb levels. Abstracts and complete articles were reviewed independently, and if the results were different, the texts were checked once again until the differences were resolved.

Statistical Analysis
Studies were combined based on means of Sb levels in prostatic tissue. The articles were analyzed and "Median of Means" and "Range of Means" were used to examine heterogeneity of Sb contents. The objective analysis was performed on data from the 23 studies, with 1173 subjects

Results
Information about Sb levels in prostatic tissue in different prostatic diseases is of obvious interest, not only to understand the etiology and pathogenesis of prostatic diseases more profoundly, but also for their diagnosis, particularly for PCa diagnosis and PCa risk prognosis [27,36]

Analytical Method
The trend line of Sb content data in "normal"

Androgen-Independence of Prostatic Sb Levels
There was not found a significant difference between Sb levels in prostates of teenagers before puberty and of post-pubertal teenagers and young adults [7,13,14]. These findings allowed us to conclude that the Sb content in "normal" prostates does not depend on the level of androgens, and vice versa.
However, studies on the association between the Sb content in "normal" prostates and the level of androgens in blood were not found.

Sb Intake
The general population can be exposed to low levels of Sb primarily through ingestion of drinking water and to a lesser degree through consumption of food and inhalation of ambient air [64]. One may also and about 12-20 mg/kg in cigarette ashes [60]. Other potential sources of Sb exposure are medications, such as tartar emetic (Sb and potassium tartrate), used to induce vomiting and in treatment of helminthic and fungal infestations [70,71].

Sb Content in Body Fluids, Tissues and Organs
It is known that Sb is accumulated primarily in liver, kidney, skeleton, thyroid, and muscle [72]. For example, mass fraction of this metalloid in liver and kidney cortex of the persons from the reference group were 0.007 and 0.005 mg/kg of wet tissue respectively [69]. The median of prostatic Sb content means obtained in the present review (0.0085 mg/kg of wet tissue) is higher the metalloid level in liver. Thus, we can conclude that the prostate is also a target organ for Sb. A small increase of Sb intake for a long period associated with a great increase of metalloid concentration in blood [67,70], and, as a consequence in different organs, including the prostate. tons annually [76]. From the polluted environment Sb is subsequently introduced into the food chain [77].
However, the major source of human exposure to Sb on unpolluted territories is naturally contaminated drinking water [66][67][68]70].