Journal of Hematology and Oncology Research

Journal of Hematology and Oncology Research

Current Issue Volume No: 4 Issue No: 1

Review-article Article Open Access
  • Available online freely Peer Reviewed
  • A Systematic Review Of The Antimony Content Of The Normal Human Prostate Gland

    1 Radionuclide Diagnostics Department, Medical Radiological Research Centre, Obninsk, 249036, Russia. 

    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 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.

    Author Contributions
    Received Dec 21, 2020     Accepted Dec 23, 2020     Published Dec 28, 2020

    Copyright© 2020 Zaichick Vladimir.
    License
    Creative Commons License   This work is licensed under a Creative Commons Attribution 4.0 International License. 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.

    Funding Interests:

    Citation:

    Zaichick Vladimir (2020) A Systematic Review Of The Antimony Content Of The Normal Human Prostate Gland Journal of Hematology and Oncology Research. - 4(1):17-27
    DOI 10.14302/issn.2372-6601.jhor-20-3673

    Introduction

    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 123. The etiology and pathogenesis of these diseases remain not well understood. A better understanding of the etiology and causative risk factors are essential for the primary prevention of these diseases.

    In our previous studies the significant involvement of trace elements (TEs) in the function of the prostate was found. 456789101112131415. It was also shown that levels of TEs in prostatic tissue, including antimony (Sb), can play a significant role in etiology of PCa 1617181920. Moreover, it was demonstrated that the changes of some TE levels and Zn/Sb ratios in prostate tissue can be used as biomarkers 21222324252627.

    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 28. This finding allowed conclude that the prostate gland accumulates Sb, because the levels of metalloid in prostates was almost four orders of magnitude higher the blood serum reference level (0.00001 mg/L) and one order of magnitude higher the liver reference level 29. Furthermore, experimental and epidemiological data identified that Sb compounds should be considered as genotoxic carcinogens 3031323334. Consequently, the International Agency for Research on Cancer (IARC) has evaluated Sb as possibly carcinogenic to humans (Group 2B) 35. These findings promoted more detailed studies of the Sb content of prostatic tissue of healthy subjects, as well as of patients with different prostatic diseases, including BPH and PCa.

    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 363738. 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 31323334. However, it still remains unclear what precise mechanism is responsible for Sb genotoxicity 3039.

    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

    Materials and Methods 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, ELSEVIER-EMBASE, Cochrane Library, and the Web of Science databases, as well as from the personal archive of the author collected between 1966 to 2020, using the key words: prostatic trace elements, prostatic Sb content, prostatic tissue, and their combinations. For example, the search terms for Sb content were: Sb mass fraction , Sb content , Sb level , prostatic tissue Sb and Sb of prostatic tissue . The language of the article was not restricted. The titles from the search results were evaluated closely and determined to be acceptable for potential inclusion criteria. Also, references from the selected articles were examined as further search tools. Relevant studies noted for the each selected article were also evaluated for inclusion.

    Eligibility Criteria Inclusion Criteria

    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.

    Exclusion Criteria

    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.

    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

    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 2736. Thus, it dictates a need for reliable values of the Sb levels in the prostatic tissue of apparently healthy subjects, ranging from young adult males to elderly persons.

    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 (Table 1) and these 23 papers 79111314242628404142434445464748495051525354 comprised the material on which the review was based.

    Reference data of Sb mass fractions (mg/kg wet tissue) in “normal” human prostatic tissue
    Reference Method n Age, rangeyears Samplepreparation Sb
    M±SD M±SD
    Zakutinsky et al. 1962 40 - - Adult - <2.9 -
    Smith 1967 28 NAA 7 Adult D 0.071 0.0051-0.275
    Liebscher et al. 1968 41 NAA 7 Adult D 0.071±0.095 0.0051-0.275
    Zaichick et al. 2011 42 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 24 NAA 37 66±8 Intact 0.0077±0.0063 0.00078-0.027
    Zaichick et al. 2012 43 ICPMS 64 13-60 AD 0.0068±0.0063 0.00136-0.027
    Zaichick et al. 2013 7 NAA 29 0-13 Intact 0.0107±0.0092 -
        21 14-30 Intact 0.0088±0.0043 -
    Zaichick et al. 2013 9 2 methods 16 20-30 Intact, AD 0.0087±0.0065 -
    Zaichick et al. 2014 44 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 45 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 11 2 methods 16 20-30 Intact, AD 0.0068±0.0036 -
    Zaichick et al. 2014 13 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 14 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 46 NAA 32 44-87 Intact 0.0068±0.0054 0.00078-0.027
    Zaichick 2015 47 2 methods 65 21-87 Intact, AD 0.0073±0.0058 -
    Zaichick et al. 2016 48 NAA 37 41-87 Intact 0.0077±0.0063 0.00078-0.027
    Zaichick et al. 2016 49 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 50 2 methods 32 44-87 Intact, AD 0.0066±0.0058 -
    Zaichick et al. 2016 51 2 methods 37 41-87 Intact, AD 0.0073±0.0061 -
    Zaichick et al. 2017 26 2 methods 37 41-87 Intact, AD 0.0073±0.0061 -
    Zaichick et al. 2017 52 2 methods 37 41-87 Intact, AD 0.0085±0,0071 0,0015-0,0305
    Zaichick 2017 53 2 methods 37 41-87 Intact, AD 0.0073±0.0062 0.00136-0.027
    Zaichick et al. 2019 54 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

    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% 55565758 and ash – 1% (on a wet mass basis) contents in normal prostates of adult men 57596061.

    (Table 1) summarizes general data from the 23 studies. The retrieved studies involved 1173 subjects. The ages of subjects were available for 20 studies and ranged from 0–87 years. Information about the analytical method and sample preparation used was available for 22 studies. One study determined Sb levels by inductively coupled plasma mass spectrometry (ICPMS) (Table 1). ICPMS is the destructive analytical method, because it requires sample acid digestion. Nine studies detected Sb level in intact prostatic tissue samples by nondestructive analytical method, such as neutron activation analysis (NAA). In twelve studies a combination of destructive and nondestructive methods (ICPMS and NAA) was used and results were summarized.

    (Figure 1) illustrates the data set of Sb measurements in 23 studies during the period from 1962 to 2020.

    Data on Sb content in “normal” prostate tissue reported from 1962 to 2020.

    Discussion

    Discussion

    The range of means of Sb mass fractions reported in the literature for normal prostatic tissue varies widely from 0.0066 mg/kg 45 to <2.9 mg/kg 40 with median of means 0.0085 mg/kg wet tissue (Table 1). The maximal value of mean Sb mass fraction reported 40 was 341 times higher the median of Sb mass fraction means and at least one order of magnitude higher than all other published means. Thus, value <2.9 mg/kg 40 can be excluded. However, without this result range of means of Sb mass fractions for normal prostatic tissue remains very wide from 0.0066 mg/kg 45 to 0.071 mg/kg 28 with median of means 0.0085 mg/kg wet tissue and Mmax/Mmin ratio approximately 11 (Table 1).

    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

    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.

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