-
Chemosphere May 2024The persistent organic pollutants (POPs) defined by the Stockholm Convention include polychlorinated naphthalenes (PCNs); of these, the most toxic, persistent, abundant,...
The persistent organic pollutants (POPs) defined by the Stockholm Convention include polychlorinated naphthalenes (PCNs); of these, the most toxic, persistent, abundant, dioxin-like congeners found in human tissues are the hexachloronaphthalenes (HxCNs). Recent research also indicates that PCNs may disrupt hormonal homeostasis. The aim of this study was to evaluate the (anti)androgenic action of HxCN. Immature, castrated male Wistar rats were exposed per os to HxCN in corn oil at daily doses ranging from 0.3 to 3.0 mg kg for 10 days. According to the OECD 441 protocol (Hershberger Bioassay), the anti-androgenic assay groups were co-exposed with testosterone propionate (TP), while the androgenic groups were not. TP was used as the reference androgen (subcutaneous daily doses of 0.4 mg kg), and flutamide (FLU) as the reference antiandrogen (per os daily doses of 3.0 mg kg). Five assessory sex tissues (ASTs) were weighed: ventral prostate, seminal vesicles, levator ani-bulbocavernosus muscle (LABC), Cowper's glands and glans penis. HxCN + TP significantly decreased the weight of the ventral prostate and seminal vesicle indicating an anti-androgenic action via 5α-reductase inhibition. These weight changes were also accompanied by abnormalities in cell morphology and hormonal disturbances: lowered levels of the testosterone and thyroid hormones thyroxine and triiodothyronine. Disturbances were also noted in the lipid profile, viz. total cholesterol, triglycerides and high-density lipoprotein and non-HDL fraction content. However, the direction of these changes differed depending on the size of the HxCN dose. No dose-effect relationship was noted for most of the obtained results; as such, exposure to even small HxCN doses run the risk of anti-androgenic effects in the general population, especially when encountered in combination with other POPs and endocrine-disrupting chemicals in the environment.
PubMed: 38763395
DOI: 10.1016/j.chemosphere.2024.142373 -
Nutrients Apr 2024Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate, associated with lower urinary tract symptoms (LUTSs). Taraxaci Herba (TH), commonly...
Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate, associated with lower urinary tract symptoms (LUTSs). Taraxaci Herba (TH), commonly known as dandelion, has traditionally been utilized in East Asia to treat symptoms related to LUTSs. Based on this traditional use, our study aimed to explore the inhibitory effects of TH on BPH progression using a testosterone propionate-induced rat model. To induce BPH, male Sprague Dawley rats were castrated and injected subcutaneously with testosterone propionate (3 mg/kg/day) for 28 days. Concurrently, TH extract was administered orally at doses of 100 and 300 mg/kg/day throughout the four-week period of testosterone propionate injections. The TH extract significantly reduced both the absolute and relative weights of the prostate, along with histopathological changes in the gland. Moreover, it lowered serum levels of testosterone and dihydrotestosterone and reduced the expression of the androgen receptor in the prostate. Additionally, the TH extract modulated the protein expressions of Bax and Bcl-2, which are key regulators of apoptosis in prostate cells. Collectively, our findings suggest that TH inhibits BPH development partially by modulating androgen signaling and inducing apoptosis within the prostate.
Topics: Male; Animals; Prostatic Hyperplasia; Testosterone Propionate; Rats, Sprague-Dawley; Prostate; Plant Extracts; Rats; Apoptosis; Disease Models, Animal; Testosterone; Receptors, Androgen; Dihydrotestosterone; bcl-2-Associated X Protein; Proto-Oncogene Proteins c-bcl-2
PubMed: 38674879
DOI: 10.3390/nu16081189 -
Frontiers in Cellular and Infection... 2024Polycystic ovary syndrome (PCOS) is a common systemic disorder related to endocrine disorders, affecting the fertility of women of childbearing age. It is associated...
Polycystic ovary syndrome (PCOS) is a common systemic disorder related to endocrine disorders, affecting the fertility of women of childbearing age. It is associated with glucose and lipid metabolism disorders, altered gut microbiota, and insulin resistance. Modern treatments like pioglitazone, metformin, and spironolactone target specific symptoms of PCOS, while in Chinese medicine, moxibustion is a common treatment. This study explores moxibustion's impact on PCOS by establishing a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Thirty-six specific pathogen-free female Sprague-Dawley rats were divided into four groups: a normal control group (CTRL), a PCOS model group (PCOS), a moxibustion treatment group (MBT), and a metformin treatment group (MET). The MBT rats received moxibustion, and the MET rats underwent metformin gavage for two weeks. We evaluated ovarian tissue changes, serum testosterone, fasting blood glucose (FBG), and fasting insulin levels. Additionally, we calculated the insulin sensitivity index (ISI) and the homeostasis model assessment of insulin resistance index (HOMA-IR). We used 16S rDNA sequencing for assessing the gut microbiota, H NMR spectroscopy for evaluating metabolic changes, and Spearman correlation analysis for investigating the associations between metabolites and gut microbiota composition. The results indicate that moxibustion therapy significantly ameliorated ovarian dysfunction and insulin resistance in DHEA-induced PCOS rats. We observed marked differences in the composition of gut microbiota and the spectrum of fecal metabolic products between CTRL and PCOS rats. Intriguingly, following moxibustion intervention, these differences were largely diminished, demonstrating the regulatory effect of moxibustion on gut microbiota. Specifically, moxibustion altered the gut microbiota by increasing the abundance of and , as well as decreasing the abundance of . Concurrently, we also noted that moxibustion promoted an increase in levels of short-chain fatty acids (including acetate, propionate, and butyrate) associated with the gut microbiota of PCOS rats, further emphasizing its positive impact on gut microbes. Additionally, moxibustion also exhibited effects in lowering FBG, testosterone, and fasting insulin levels, which are key biochemical indicators associated with PCOS and insulin resistance. Therefore, these findings suggest that moxibustion could alleviate DHEA-induced PCOS by regulating metabolic levels, restoring balance in gut microbiota, and modulating interactions between gut microbiota and host metabolites.
Topics: Animals; Polycystic Ovary Syndrome; Female; Moxibustion; Gastrointestinal Microbiome; Rats, Sprague-Dawley; Rats; Disease Models, Animal; Insulin Resistance; Dehydroepiandrosterone; Blood Glucose; Insulin; Metformin; Testosterone; Ovary
PubMed: 38665877
DOI: 10.3389/fcimb.2024.1328741 -
The World Journal of Men's Health Apr 2024The aim of this study was to investigate the efficacy of ethanol extracts of (ECA) against benign prostatic hyperplasia (BPH) and .
Ethanol Extracts of Improve Benign Prostatic Hyperplasia by Inhibiting Prostate Cell Proliferation through Modulating 5 Alpha-Reductase/Androgen Receptor Axis-Mediated Signaling.
PURPOSE
The aim of this study was to investigate the efficacy of ethanol extracts of (ECA) against benign prostatic hyperplasia (BPH) and .
MATERIALS AND METHODS
The prostate stromal cells (WPMY-1) and epithelial cells (RWPE-1) were used to examine the action mechanism of ECA in BPH . ECA efficacy was evaluated using a testosterone propionate (TP)-induced BPH rat model.
RESULTS
Treatment with ECA inhibited the proliferation of prostate cells by inducing G1-phase cell cycle arrest through the regulation of positive and negative proteins. Treatment of prostate cells with ECA resulted in alterations in the mitogen-activated protein kinases and protein kinase B signaling pathways. The transcriptional binding activity of the NF-κB motif was suppressed in both ECA-treated prostate cells. In addition, treatment with ECA altered the level of BPH-associated axis markers (5α-reductase, fibroblast growth factor-2, androgen receptor, epidermal growth factor, Bcl-2, and Bax) in both cell lines. Finally, the administration of ECA attenuated the enlargement of prostatic tissues in the TP-induced BPH rat model, accompanied by histology, immunoblot, and serum dihydrotestosterone levels.
CONCLUSIONS
These results demonstrated that ECA exerted beneficial effects on BPH both and and might provide valuable information in the development of preventive or therapeutic agents for improving BPH.
PubMed: 38606866
DOI: 10.5534/wjmh.230200 -
Food and Chemical Toxicology : An... Jun 2024Testes are very prone to be damaged by environmental pollutants, but there is a lack of information about the impact of "chemical cocktails" (CC) on the testicular...
Testes are very prone to be damaged by environmental pollutants, but there is a lack of information about the impact of "chemical cocktails" (CC) on the testicular metabolome and the possible influence in the gut-gonad crosstalk. For this, BALB/c mice were given flumequine and diclofenac orally in food and potentially toxic trace elements (Cd, Hg, As) in drinking water. A mice group was supplemented with selenium, a well-known antagonist against many pollutants. Our results revealed that the steroid 5-alpha-androstan-17-beta-ol propionate, suggested as a parameter of androgenicity independent of testosterone levels, proline that improves reproductive indicators in male rabbits affected by environmental stress) among others metabolites are only present after CC exposure with rodent and selenium supplemented diet. Selenium also antagonized the up-or down-regulation of anandamide (20:l, n-9) (p < 0.001 and FC 0.54 of CC vs C but p > 0,05 and FC 0.74 of CC-Se vs C), that regulates gonadotropin-releasing hormones in mammals, 2,3-dinor-11b-PGF2a (p < 0.001 and FC 0.12 of CC vs C but p > 0,05 and FC 0.34 of CC-Se vs C), which has been related with reproductive hormones, besides others testicular metabolites altered by the exposure to the CC and reversed the levels to control. Moreover, numerous significant associations between gut microbes and testicular metabolites indicated a possible impact of pollutants in the testes mediated by gut microbiota due to a gut-gonad crosstalk.
Topics: Animals; Male; Mice, Inbred BALB C; Metabolomics; Mice; Testis; Gastrointestinal Microbiome; Diclofenac
PubMed: 38561037
DOI: 10.1016/j.fct.2024.114627 -
Molecular Medicine (Cambridge, Mass.) Mar 2024Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also...
BACKGROUND
Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland.
METHODS
Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay.
RESULTS
In vivo, Itln-1 mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation.
CONCLUSION
The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.
Topics: Humans; Male; Mice; Animals; Aged; Prostatic Hyperplasia; Tumor Necrosis Factor-alpha; Plant Extracts; Prostate; Inflammation
PubMed: 38519941
DOI: 10.1186/s10020-024-00805-y -
Biological & Pharmaceutical Bulletin 2024To clarify the causes of sex differences (male < female) in the serum total cholesterol (TCHO) and triglyceride (TG) levels in Meishan pigs, we examined the sex...
To clarify the causes of sex differences (male < female) in the serum total cholesterol (TCHO) and triglyceride (TG) levels in Meishan pigs, we examined the sex differences in mRNA levels of key hepatic enzymes involved in the biosynthesis/metabolism of cholesterol and TG using real-time RT-PCR. There were no sex differences in mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase and CYP51A1 for cholesterol biosynthesis, or of the rate-limiting enzyme CYP7A1 for bile acid synthesis from cholesterol. By contrast, sex differences (male < female) were observed in mRNA levels of glycerol-3-phosphate acyltransferase 1 (GPAT1), a rate-limiting enzyme for TG biosynthesis. However, the sex differences in mRNA levels of carnitine palmitoyltransferase 1A (CPT1A) and acyl-CoA dehydrogenase long chain (ACADL), key enzymes for the oxidation of the fatty acids that are structural components of TG, were the opposite (male > female). Castration of male pigs led to an increase in the mRNA level of GPAT1 and decreases in those of CPT1A and ACADL. Furthermore, testosterone propionate (TP)-treatment of castrated males and intact females restored and changed, respectively, these mRNA levels to those of intact males. Notably, castration and TP-treatment increased and decreased, respectively, serum and hepatic TG levels. These findings suggest that sex differences in the serum and hepatic TG levels in Meishan pigs are closely correlated with differences in testosterone-associated mRNA expression levels of the key enzymes (GPAT1, CPT1A, and ACADL) involved in the TG biosynthesis process, although no causes of sex differences in serum and hepatic TCHO levels could be found.
Topics: Swine; Female; Male; Animals; Sex Characteristics; Liver; Cholesterol; Testosterone Propionate; Triglycerides; RNA, Messenger; Lipid Metabolism
PubMed: 38462492
DOI: 10.1248/bpb.b23-00895 -
Journal of Ethnopharmacology Apr 2024Jiawei Buzhong Yiqi Decoction (JWBZYQ), from records of FuqingzhuNvke, is a classical formula for treating obese women related infertility. JWBZYQ has been shown to be...
ETHNOPHARMACOLOGICAL RELEVANCE
Jiawei Buzhong Yiqi Decoction (JWBZYQ), from records of FuqingzhuNvke, is a classical formula for treating obese women related infertility. JWBZYQ has been shown to be effective in treating polycystic ovary syndrome (PCOS) in both clinical studies and practical practice, with the pharmacological mechanism remaining unknown.
AIM OF THE STUDY
To explore the potential therapeutic effects and mechanistic insights of JWBZYQ in PCOS.
MATERIALS AND METHODS
An overweight PCOS rat model was established via testosterone propionate (TP) injection and 45% high-fat diet (HFD). Then they were categorized into five distinct groups: Control group, Model group, low-dose of JWBZYQ (JWBZYQ1) group, high-dose of JWBZYQ (JWBZYQ2) group, and metformin (Met) group. Body weight, estrous cycle, and sex hormone levels were observed. Hematoxylin-Eosin staining was employed to investigate the histological characteristics of the ovaries. To identify the pathways that changed significantly, transcriptome analysis was performed. The protein and mRNA levels of key molecules in ovarian zona pellucida (ZP) organization, transzonal projections (TZPs) assembly, steroid hormone receptors, and steroidogenesis were assessed using phalloidin staining, immunohistochemistry, Western blot, and polymerase chain reaction.
RESULTS
RNA-seq analysis demonstrated that regulation of hormone secretion, cilium assembly, cell projection assembly, and ZP production may all have crucial impact on the etiology of PCOS and therapeutic effect of JWBZYQ. In particular, PCOS rats exhibited elevated expressions of ZP1-3, which can be reversed by JWBZYQ2 particularly. Simultaneously, TZPs assembly was totally disrupted in PCOS rats, evidenced by the phalloidin staining, upregulated calcium-/calmodulin-dependent protein kinase II beta (CaMKIIβ), and deficient p-CaMKIIβ, myosin X (MYO10), proline-rich tyrosine kinase 2 (PTK2), and Fascin. Nonetheless, JWBZYQ or metformin treatment revived the disturbance, repairing the oocyte-granulosa cell communication, regulating steroidogenesis in PCOS rats. In this way, JWBZYQ and metformin exerted remarkable effects in alleviating altered ovarian morphology and function in PCOS rats, with JWBZYQ2 revealing the best effect.
CONCLUSIONS
JWBZYQ restored the altered ovarian morphology and function by regulating the oocyte-granulosa cell communication, which was related with ZP organization and TZPs assembly in the ovary.
Topics: Humans; Rats; Female; Animals; Polycystic Ovary Syndrome; Phalloidine; Oocytes; Metformin; Cell Communication; Hormones
PubMed: 38158097
DOI: 10.1016/j.jep.2023.117654 -
BMC Urology Dec 2023Benign prostatic hyperplasia (BPH) is a major health concern associated with lower urinary tract symptoms and sexual dysfunction in men. Recurrent inflammation,...
BACKGROUND
Benign prostatic hyperplasia (BPH) is a major health concern associated with lower urinary tract symptoms and sexual dysfunction in men. Recurrent inflammation, decreased apoptotic rate and oxidative stress are some of the theories that explain the pathophysiology of BPH. Common salt, a food additive, is known to cause systemic inflammation and redox imbalance, and may serve as a potential risk factor for BPH development or progression. This study examined the effect of common salt intake on the pathology of testosterone-induced BPH.
METHODS
Forty male Wistar rats were randomly divided into four equal groups of 10: a control and three salt diet groups-low-salt diet (LSD), standard-salt diet (SSD) and high-salt diet (HSD). The rats were castrated, allowed to recuperate and placed on salt-free diet (control), 0.25% salt diet (LSD), 0.5% salt diet (SSD) and 1.25% salt diet (HSD) for 60 days ad libitum. On day 33, BPH was induced in all the rats with daily injections of testosterone propionate-Testost® (3 mg/kg body weight) for 28 days. The rats had overnight fast (12 h) on day 60 and were euthanized the following day in order to collect blood and prostate samples for biochemical, molecular and immunohistochemistry (IHC) analyses. Mean ± SD values were calculated for each group and compared for significant difference with ANOVA followed by post hoc test (Tukey HSD) at p < 0.05.
RESULTS
This study recorded a substantially higher level of IL-6, IL-8 and COX-2 in salt diet groups and moderate IHC staining of COX-2 in HSD group. The prostatic level of IL-17, IL-1β, PGE2, relative prostate weight and serum PSA levels were not statistically different. The concentrations of IGF-1, TGF-β were similar in all the groups but there were multiple fold increase in Bcl-2 expression in salt diet groups-LSD (13.2), SSD (9.5) and HSD (7.9) and multiple fold decrease in VEGF expression in LSD (-6.3), SSD (-5.1) and HSD (-14.1) compared to control. Activity of superoxide dismutase (SOD) and concentration of nitric oxide rose in LSD and SSD groups, and SSD and HSD groups respectively. Activities of glutathione peroxidase and catalase, and concentration of NADPH and hydrogen peroxide were not significantly different. IHC showed positive immunostaining for iNOS expression in all the groups while histopathology revealed moderate to severe prostatic hyperplasia in salt diet groups.
CONCLUSIONS
These findings suggest that low, standard and high salt diets aggravated the pathology of testosterone-induced BPH in Wistar rats by promoting inflammation, oxidative stress, while suppressing apoptosis and angiogenesis.
Topics: Humans; Male; Rats; Animals; Testosterone; Prostatic Hyperplasia; Rats, Wistar; Cyclooxygenase 2; Inflammation
PubMed: 38082261
DOI: 10.1186/s12894-023-01371-x -
Journal of Microbiology and... May 2024Oxidative stress is a key factor in the pathogenesis of benign prostatic hyperplasia (BPH) that leads to inflammation. This study aimed to evaluate the ameliorative...
Oxidative stress is a key factor in the pathogenesis of benign prostatic hyperplasia (BPH) that leads to inflammation. This study aimed to evaluate the ameliorative effects of Bunge extract (HLT-101) on BPH through the regulation of oxidative stress and inflammation. A testosterone propionate (TP)-induced BPH rat model was orally administered HLT-101 (20, 40, or 80 mg/kg), and its effects on oxidative stress- and inflammation-related gene expression were examined. Further, HLT-101 was assessed for its effect on reactive oxygen species (ROS) levels and Nrf-2/HO-1 signaling pathways in BPH-1 cells. HLT-101 decreased testosterone-induced excessive free radical production and inflammatory factor activation. Moreover, HLT-101 treatment significantly decreased the intracellular ROS level in the TNF-α and IFN-γ treated BPH-1 cells through the activation of Nrf-2. In addition, HLT-101 treatment inhibited the NF-κB pathway and androgen receptor (AR) signaling, which is highly linked to the pathogenesis of BPH. Therefore, HLT-101 has the potential to be an effective treatment reagent for BPH because of its ability to reduce inflammation and oxidative stress via Nrf-2/HO-1 signaling.
Topics: Male; Salvia miltiorrhiza; Prostatic Hyperplasia; Oxidative Stress; Animals; NF-E2-Related Factor 2; Rats; Reactive Oxygen Species; Signal Transduction; Plant Extracts; Heme Oxygenase-1; Humans; Rats, Sprague-Dawley; Disease Models, Animal; Cell Line; NF-kappa B; Testosterone Propionate
PubMed: 37994101
DOI: 10.4014/jmb.2308.08053