Alteration of testicular steroidogenesis and histopathology of reproductive system in male rats treated with triclosan
Introduction
Endocrine-disrupting chemicals (EDC) comprise a category of environmental contaminants that interferes with the function of endocrine system [1]. An increasing body of evidence reveals an association between various environmental compounds that act as EDC and lead to sex hormone-sensitive disease/disorders [2], [3]. Chemicals that mimic the structure of the natural hormones found in the animal/human body may pose species-specific risks that are difficult to investigate because of latent adverse effects [4]. A body of literature exists for various EDC demonstrating potential estrogenic activities which have been identified and classified [2]. Although there are similar health concerns regarding (anti)androgenic EDC that interfere with sperm production, alter genital development and contribute to neurological syndromes in males, the identification and classification of these putative health hazards have progressed comparatively slowly [3]. Recent reports of several non-steroidal compounds that have the ability to alter the androgen dependent functions are of particular concern because many of them are ubiquitously used in our daily life.
A number of antimicrobial agents and preservatives are commonly used in the personal care products such as soaps, shampoos, detergents, disinfectants, cosmetics and pharmaceutical products [5], [6], [7]. The continuous use of these chemicals results in their accumulation at detectable concentrations within different parts of our body like blood, milk, and various organs and tissues [5], [8], [9], [10]. Triclosan (TCS; 2,4,4′-trichloro-2′-hydroxydiphenyl ether; a chlorophenol) is an antimicrobial agent widely used as preservative in toothpastes, soaps, shampoos, and cosmetics [11]. The chemical structure is shown in Fig. 1. In general, TCS has been known to be a highly toxic chemical for aquatic flora and fauna [12] and thus has been included in the probable list of endocrine disruptors on account of its resemblance with known non-steroidal estrogens or its mimetic (e.g. diethylestradiol, bisphenol A). Further, TCS and its chlorinated derivatives are readily converted into various chlorinated dibenzo-p-dioxins by heat and ultraviolet irradiation which may also be harmful for biological systems [13], [14], [15]. The mode of action of TCS as an EDC is controversial and various studies indicate it to be of different nature, viz. estrogenic or weak androgenic or anti-androgenic. Fourteen days TCS exposure in Japanese medaka fry (Oryzias latipes) showed a weak androgenic effect [16]. Another study reported that the metabolite of TCS may be a weak estrogenic compound with the potential to induce vitellogenin in male medaka while decreasing the hatchability, as well as delaying the hatching in females [17]. TCS has also been shown to function as an anti-androgen since it inhibits testosterone-induced transcriptional activity [2]. Exposure of TCS to the human may be a consequence of its presence in the cosmetics and other human use products. This chemical has been reported to be absorbed mainly by two routes: either across the skin or through the gastrointestinal tract [8].
This report describes the various targets of TCS toxicity in an effort to help understand its probable mode of action as an (anti)androgenic endocrine disruptor using male albino rats as model. The rats were treated with three dose levels of TCS for a fixed period of time. On completion of treatment serum and tissue samples were analyzed for their (anti)androgenic effects in response to TCS. Further histopathological analysis of testis and sex accessory tissues (SATs) were performed to assess the action of this chemical at the cellular levels. The data presented here demonstrates that some widely used antimicrobial compounds like that of TCS have anti-androgenic properties and warrant further investigation to understand its impact on human reproductive health.
Section snippets
Animals
The study was carried out on the male Wistar rats, Rattus norvegicus, with the approval as well as guidelines of institutional ethical committee. Animals were purchased from All India Institute of Medical Sciences (New Delhi, India) and were in healthy condition at the time of purchasing. They were housed in a well-ventilated animal house with 12 h light:12 h dark schedule. The animals were fed with a balanced animal diet obtained commercially (Ashirwad Animal Feed Industries, Punjab, India) and
Body weight and weight of testis and SATs
Treatment of rats with test samples did not induce significant changes in the body weight at any of the test doses (Table 2). Whatever minimal increase in the body weight observed could be attributed to normal aging. Administration of TCS did not cause significant change in the weight of testis and SATs at the 5 mg/(kg day) dosage. In contrast, the higher test doses (10 and 20 mg/(kg day)) induced a significant decrease in the weight of testis and SATs. TCS exposure decreased the weights of testis,
Discussion
TCS is a synthetic chemical widely used as an antimicrobial agent in different commercial preparations [11]. Since TCS possess a phenolic moiety like many of the common EDC it could be presumed to display similar activities as demonstrated by other EDC of the same chemical family [31], [32]. The dosage for the test chemicals used in this study were selected based on LD50 values and also some earlier reports where a similar compound, triclocarbon (TCC), was used in rat models [33], [34]. In this
Conflict of interest
None declared.
Acknowledgements
Kind help of Prof. Ilpo Huhtaniemi, Imperial College London, UK with all steroidal test chemicals is greatly acknowledged. We would also like to thank Prof. D.M. Stocco, Texas Tech University, Lubbock, TX, and Dr. R.K. Tyagi, Jawaharlal Nehru University, New Delhi, India for kindly providing the StAR and androgen receptor antibodies, respectively. The study was supported by the Ministry of Human Resource and Development as fellowship to V.K., and by the Department of Biotechnology (DBT, no.
References (56)
- et al.
Assessment of river contamination by estrogenic compounds in Paris area (France)
Sci Tot Environ
(2004) - et al.
Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products
Toxicol Appl Pharmacol
(2007) Environmental oestrogens, cosmetics and breast cancer
Res Clin Endocrinol Metab
(2006)- et al.
Elimination of endocrine disrupting chemicals nonylphenol and bisphenol A and personal care product ingredient triclosan using enzyme preparation from the white rot fungus Coriolopsis polyzona
Chemosphere
(2007) - et al.
Pharmaceutical chemicals and endocrine disrupters in municipal wastewater in Tokyo and their removal during activated sludge treatment
Water Res
(2006) - et al.
Percutaneous absorption and metabolism of Irgasan DP 300
Toxicology
(1975) - et al.
Chlorination of Irgasan DP300 and formation of dioxins from its chlorinated derivatives
J Chromatogr
(1987) - et al.
Developmental evaluation of a potential non-steroidal estrogen: triclosan
Mar Environ Res
(2000) - et al.
Effects of triclosan on the early life stages and reproduction of medaka Oryzias latipes and induction of hepatic vitellogenin
Aquat Toxicol
(2004) - et al.
Triclosan: applications and safety
Am J Infect Control
(1996)
Effect of atenolol on cadmium induced testicular toxicity in male rats
Reprod Toxicol
Steroids
Reproductive effects in male rats exposed to diuron
Reprod Toxicol
Single step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction
Anal Biochem
Effects of vitamins C and E on steroidogenic enzymes mRNA expression in polychlorinated biphenyl (Aroclor 1254) exposed adult rat Leydig cells
Toxicology
Interaction of thyroid hormone and steroidogenic acute regulatory (StAR) protein in the regulation of murine Leydig cell steroidogenesis
J Steroid Biochem Mol Biol
Phosphorylation of steroidogenic acute regulatory protein (StAR) modulates its steroidogenic activity
J Biol Chem
Gene regulation of steroidogenesis
J Steroid Biochem Mol Biol
Effect of PCB-based transformer oil on testicular steroidogenesis and xenobiotic-metabolizing enzymes
Reprod Toxicol
Phytoestrogens and their low dose combinations inhibit mRNA expression and activity of aromatase in human granulosa-luteal cells
J Steroid Biochem Mol Biol
Testicular toxicity of boric acid (BA): relationship of dose to lesion development and recovery in the F334 rat
Reprod Toxicol
A broad-spectrum organophosphate pesticide O,O-dimethyl O-4-nitrophenyl phosphorothioate (methyl parathion) adversely affects the structure and function of male accessory reproductive organs in the rat
Environ Toxicol Pharmacol
Androgenic endocrine disruptors in wastewater treatment plant effluents in India: their influence on reproductive processes and systemic toxicity in male rats
Toxicol Appl Pharmacol
Endocrine-disrupting compounds and mammary gland development: early exposure and later life consequences
Endocrinology
Paraben transport and metabolism in the biomimetic artificial membrane permeability assay (BAMPA) and 3-day and 21-day Caco-2 cell systems
J Biomol Screen
Response to: ethics, data and the pharmaceutical physician
Int J Clin Pract
Partitioning, persistence and accumulation in digested sludge of the topical antiseptic triclocarban during wastewater treatment
Environ Sci Technol
K Effects of triclosan on various aquatic organisms
Environ Sci
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2022, ChemosphereCitation Excerpt :In general, much discrepancy is observed between the results, but this discrepancy can be explained by the doses and the exposure times. For example, at low exposure doses (0.8–20 mg/kg/day), no significant variation is found by TCS exposure in the weight of rats at the end of the studies independent of sex, pregnancy or period of treatment (varying from 3 days to 13 weeks) (Garcia et al., 2018; Kumar et al., 2009; Ena et al., 2018; Rabaglino et al., 2016). In other studies where the dose is similar to that proposed here (37.5 mg/kg/day), a significant effect was found of weight loss after 32 weeks of exposure (Louis et al., 2017), which coincides with what was reported in our work but in a much shorter period (4 weeks).
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- 1
Present address: Department of Biotechnology, The ICFAI University, Dehradun, Rajawala Road, Dehradun 248197, Uttarakhand, India.
- 2
Contributed equally to this work.