The authors have declared that no competing interests exist.
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
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.
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
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 (
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 |
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%
(
(
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.
The trend line of Sb content data in “normal” prostate (
In one reported paper such destructive analytical method as ICP-MS was used. This method requires acid digestion of the samples at a high temperature. There is evidence that use of this treatment causes some quantities of TEs to be lost
In a few studies which used the comparison of different age groups or the Pearson’s coefficient of correlation between age and Sb content in prostate tissue it was not found a significant changes in Sb content with increasing age
There was not found a significant difference between Sb levels in prostates of teenagers before puberty and of post-pubertal teenagers and young adults
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
It is known that Sb is accumulated primarily in liver, kidney, skeleton, thyroid, and muscle
All natural chemical elements of the Periodic System, including Sb, present in all subjects of biosphere
The situation with using Sb began to change after the industrial revolution, particularly, over the last 100 years. The primary use of Sb is in industry. For example, very pure Sb is used to make certain types of semiconductor devices, such as diodes and infrared detectors. Sb alloys are used in lead-acid batteries, low friction metals, type metal, cable coverings, microelectronics, solders, bullets and bearings, and in pewter (an alloy of tin, copper and Sb). Other uses of Sb compounds include as a pigment in paints, textiles and glass industries, as well as in the production of the thermoplastic polymer polyethylene terephthalate. Sb compounds is also used in the manufacture of flame-retardant or flame-proofing materials (rubber, plastics, pigments, adhesives, textiles, and paper), as well as in production of some medications and antiprotozoal veterinary drugs
Thus, inorganic Sb is ubiquitously distributed in environment and food, water, and air everywhere contain this element. In addition to the abundant natural sources of Sb, there are a large number of industrial sources of Sb to the soil (through atmospheric emissions originating from residues from coal, oil, and gas combustion, urban refuse, Au, Cu, Pb, Sb, and Zn mine tailings, smelter slag, waste, including pharmaceutical waste), water (through irrigation and industrial liquid waste, livestock dips, and wastewater sludge application), and air (Sb may be released from metal smelters and from combustion of fossil fuels) contamination. For example, in 1979 year the anthropogenic emission of Sb was estimated as 38,000 tons annually
Sb is an important product in the world economy. Most of the Sb mined today comes from China, which supplies approximately 90% of the world's total. In the end of past century Sb annual production was about 50.000 tons per year but in 2015, the total global volume of Sb production was already approximately 175,500 metric tons. Some Sb is produced as a by-product of smelting ores of metals, mainly gold, copper and silver, in countries such as the United States, Canada, and Australia. Since the use of Sb is linked to the rapidly developing modern technology, we can assume that over the years, the need of industry in this metalloid has increased significantly and would continue to increase in the future.
As mentioned above, an ingestion of Sb by humans can cause a variety of disorders, such as irritation of the eyes, severe vomiting, diarrhea, skin lesions, lung diseases, heart problems, stomach ulcers
Thus, according our study for unpolluted areas there are no information could explain the variability of published means for “normal” prostatic Sb levels from 0.0066 mg/kg to 0.071 mg/kg of wet tissue. Moreover, prostate tissue Sb contents showed large variations among individuals, but sources of the variation remain unknown. It is, therefore, reasonable to assume from data of our study that inaccuracy of analytical technologies employed caused so great variability of published means for prostatic Sb levels. This conclusion was supported the fact that the Certified Reference Materials for quality control of results were not used in old studies.
There are some limitations in our study, which need to be taken into consideration when interpreting the results of this review. The sample size of each study was sometimes relatively small (from 7 to 65), and a total of 1173 “normal” prostates were investigated from all 23 studies. As such, it is hard to draw definite conclusions about the reference value of the Sb content in “normal” prostate as well as about the clinical value of the Sb levels in “normal” prostates as a biomarker.
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.