Abstract
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
Author Contributions
Copyright© 2020
Zaichick Vladimir.
License
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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Competing interests The authors have declared that no competing interests exist.
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Introduction
The prostate gland is subject to various disorders and of them chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) are extremely common diseases of ageing men In our previous studies the significant involvement of trace elements (TEs) in the function of the prostate was found. It was indicated low levels of Sb in human prostatic tissue (0.071 mg/kg of wet tissue) in studies published more than 50 years ago The effects of TEs, including Sb, are related to their concentration. Recorded observations range from a deficiency state, through normal function as biologically essential components, to an imbalance, when excess of one element interferes with the function of another, to pharmacologically active concentrations, and finally to toxic and even life-threatening concentrations 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.
Materials And Methods
Aiming at finding the most relevant articles for this review, a thorough comprehensive web search was conducted by consulting the PubMed, Scopus, ELSEVIER-EMBASE, Cochrane Library, and the Only papers with quantitative data of Sb prostatic content were accepted for further evaluation. Studies were included if the control groups were healthy human males with no history or evidence of urological or other andrological disease and Sb levels were measured in samples of prostatic tissue. Studies were excluded if they were case reports. Studies involving subjects that were Sb occupational exposed, as well as persons from Sb contaminated area were also excluded. 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. 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 Possible publications relevant to the keywords were retrieved and screened. A total of 1998 publications were primarily obtained, of which 1975 irrelevant papers were excluded. Thus, 23 studies were ultimately selected according to eligibility criteria that investigated Sb levels in tissue of normal prostates ( A number of values for Sb mass fractions were not expressed on a wet mass basis by the authors of the cited references. However, we calculated these values using the medians of published data for water – 83% ( (
Reference
Method
n
Age, rangeyears
Samplepreparation
Sb
M±SD
M±SD
Zakutinsky et al. 1962
-
-
Adult
-
<2.9
-
Smith 1967
NAA
7
Adult
D
0.071
0.0051-0.275
Liebscher et al. 1968
NAA
7
Adult
D
0.071±0.095
0.0051-0.275
Zaichick et al. 2011
NAA
64
13-60
Intact
0.0085±0.0063
0.00085-0.027
9
13-20
Intact
0.0083±0.0061
-
28
21-40
Intact
0.0094±0.0060
-
27
41-60
Intact
0.0078±0.0068
-
Zaichick et al. 2012
NAA
37
66±8
Intact
0.0077±0.0063
0.00078-0.027
Zaichick et al. 2012
ICPMS
64
13-60
AD
0.0068±0.0063
0.00136-0.027
Zaichick et al. 2013
NAA
29
0-13
Intact
0.0107±0.0092
-
21
14-30
Intact
0.0088±0.0043
-
Zaichick et al. 2013
2 methods
16
20-30
Intact, AD
0.0087±0.0065
-
Zaichick et al. 2014
NAA
28
21-40
Intact
0.0094±0.0058
0.00153-0.027
27
41-60
Intact
0.0078±0.0070
0.00078-0.027
10
61-87
Intact
0.0068±0.0036
0.00187-0.0121
Zaichick et al. 2014
2 methods
28
21-40
Intact, AD
0.0077±0.0053
0.00153-0.027
27
41-60
Intact, AD
0.0075±0.0068
0.0017-0.027
10
61-87
Intact, AD
0.0066±0.0044
0.00136-0.015
Zaichick et al. 2014
2 methods
16
20-30
Intact, AD
0.0068±0.0036
-
Zaichick et al. 2014
NAA
29
0-13
Intact
0.014±0.012
-
21
14-30
Intact
0.010±0.005
-
50
0-30
Intact
0.0121±0.0094
-
Zaichick et al. 2014
2 methods
50
0-30
Intact, AD
0.0108±0.0087
-
29
0-13
Intact, AD
0.013±0.011
-
21
14-30
Intact, AD
0.0086±0.0049
-
Zaichick et al. 2015
NAA
32
44-87
Intact
0.0068±0.0054
0.00078-0.027
Zaichick 2015
2 methods
65
21-87
Intact, AD
0.0073±0.0058
-
Zaichick et al. 2016
NAA
37
41-87
Intact
0.0077±0.0063
0.00078-0.027
Zaichick et al. 2016
2 methods
28
21-40
Intact, AD
0.0092±0.0063
-
553085100012500
27
41-60
Intact, AD
0.0091±0.0088
-
10
61-87
Intact, AD
0.0084±0.0060
-
37
41-87
Intact, AD
0.0089±0.0013
-
65
21-87
Intact, AD
0.0091±0.0070
-
Zaichick et al. 2016
2 methods
32
44-87
Intact, AD
0.0066±0.0058
-
Zaichick et al. 2016
2 methods
37
41-87
Intact, AD
0.0073±0.0061
-
Zaichick et al. 2017
2 methods
37
41-87
Intact, AD
0.0073±0.0061
-
Zaichick et al. 2017
2 methods
37
41-87
Intact, AD
0.0085±0,0071
0,0015-0,0305
Zaichick 2017
2 methods
37
41-87
Intact, AD
0.0073±0.0062
0.00136-0.027
Zaichick et al. 2019
2 methods
37
41-87
Intact, AD
0.0073±0.0062
0.00136-0.027
Median of means
0.0085
Range of means (Mmin - Mmax),
0.0066 – 2.90
Ratio Mmax/Mmin
(<2.90/0.0066) = <439
All references
23
Discussion
The range of means of Sb mass fractions reported in the literature for normal prostatic tissue varies widely from 0.0066 mg/kg This variability of reported mean values can be explained a priori by a dependence of Sb content on many factors, including analytical method imperfections, differences in normal prostate definitions, possible non-homogeneous distribution of Sb levels throughout the prostate gland volume, age, ethnicity, diet, smoking, alcohol intake, consuming supplemental trace elements, and others. Not all these factors were strictly controlled in the cited studies. For example, in some studies the normal prostate means a gland of an apparently healthy man who had died suddenly, but without any morphological confirmation of normality of his prostatic tissue. In other studies the normal prostate means a non-cancerous prostate (but hyperplastic and inflamed glands were included) and even a visually normal prostatic tissue adjacent to a prostatic malignant tumor. Some researchers used as the normal prostate the glands of patients who died from acute and chronic non-prostatic diseases including subjects who had suffered from prolonged wasting illnesses. In some studies whole glands were used for the investigation while in others the Sb content was measured in pieces of the prostate. Therefore published data allowed us to estimate the effect of only some different factors on Sb content in normal prostate tissue.
Conclusion
The present study is a comprehensive study regarding the determination of Sb content in “normal” human prostates. With this knowledge Sb levels may then be considered as a biomarker for the recognition of prostate disorders. The study has demonstrated that level of Sb in “normal” prostates depends on many unknown factors. Because of the uncertainties we have outlined, we recommend other primary studies be performed.