Research Article
Relationship Between Serum Vitamin D and Adrenal-derived Androgens Upon Castrate-Resistant Prostate Cancer Diagnosis
Issue:
Volume 9, Issue 1, June 2025
Pages:
1-11
Received:
10 January 2025
Accepted:
27 January 2025
Published:
17 February 2025
Abstract: Introduction: Following primary androgen deprivation therapy (PADT) for prostate cancer (PCa) treatment, most patients develop castration-resistant PCa (CRPC). Intra-prostatic biosynthesis of androgens from adrenal-derived precursor androgens promotes CRPC evolution after PADT and vitamin D (VitD) have been shown to inhibit this intra-prostatic biosynthesis. However, the relationship between VitD and these adrenally-derived androgens in PCa patients who later develop CRPC following PADT is unknown, hence, this study. Methods: This prospective longitudinal study was conducted among locally advanced PCa patients in the Department of Chemical Pathology at the Rivers State University Teaching Hospital, Southern Nigeria. Patients were followed up for 36 months (January 2021 to December 2023) from when they had surgical PADT until they developed CRPC. Relevant data were obtained at 4-time points during the studied period: at PCa diagnosis before PADT, at PADT commencement, at the attainment of castrate status following PADT, and at CRPC evolution/diagnosis to evaluate the influence of VitD on adrenal-derived androgens [dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), androstenedione (A-dione), 5-androstenediol (5-adiol), and 11-keto-testosterone (11-KT)] in CRPC. Descriptive/inferential parameters were used to evaluate data at an alpha value of <0.05. Results: At baseline before PADT, the majority of the study cohorts (n=220) had VitD deficiency (n=121; 55.0%) compared to those with VitD insufficiency (n=72; 32.7%) and VitD sufficiency (n=27; 12.3%). At the attainment of castrate status following PADT, the VitD deficient cohorts had a longer duration to attain castrate status, a shorter time to attain TPSA nadir, and higher serum TT levels (p<0.05, respectively). At the attainment of CRPC status, 47 subjects developed CRPC with the majority (n=24; 51.0%) having VitD deficiency compared to the VitD insufficient (n=13; 27.7%) and VitD sufficient cohorts (n=10; 21.3%). The VitD-deficient cohorts also had a shorter time to CRPC onset following PADT and higher serum total prostate-specific antigen (TPSA), total testosterone (TT), and adrenal-derived androgens (DHEA, DHEAS, A-dione, 5-adiol, and 11-KT) levels compared to the VitD insufficient/sufficient cohorts (p<0.05, respectively). Moreover, the CRPC cohorts had higher serum levels of adrenocorticotropic hormone (ACTH), TT, TPSA, free testosterone, bio-available testosterone, and adrenal-derived androgens but lower VitD than the non-CRPC cohorts (p<0.05, respectively). An inverse relationship was observed between VitD and the adrenal-derived androgens among all CRPC cohorts which were more amplified among the VitD-deficient CRPC cohorts (p<0.05). Conclusion: Current findings indicate the role of VitD in CRPC through its influence on the adrenal-derived androgens. However, further studies are recommended to verify these findings and their clinical implications.
Abstract: Introduction: Following primary androgen deprivation therapy (PADT) for prostate cancer (PCa) treatment, most patients develop castration-resistant PCa (CRPC). Intra-prostatic biosynthesis of androgens from adrenal-derived precursor androgens promotes CRPC evolution after PADT and vitamin D (VitD) have been shown to inhibit this intra-prostatic bio...
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Research Article
Omega-3 Fatty Acids as a Novel Antioxidant Strategy Against Cadmium-induced Testicular Dysfunction: A Proteomic Approach
Fidelis Ohiremen Oyakhire*
,
Mathias Abiodun Emokpae,
Kelly Iria Esezobor,
Babatunde Ishola Gabriel Adejumo,
Samson Efenarhua,
Juliana Edusola Olaniyan,
Emmanuel Onosetale Afeikhena,
Adolphus Osakpolor Ogbebor,
Aigbokan Akhere Caleb,
Eboselume Osamudiamen Joshua,
Vani Onotinamhe Usman-Onoruvie,
Patricia Ejenawome Dele-Ochie,
Grace Eleojo Obasuyi,
Basheer Madompoyil,
Sadeeq Abdulsalam
Issue:
Volume 9, Issue 1, June 2025
Pages:
12-31
Received:
27 June 2025
Accepted:
14 July 2025
Published:
7 August 2025
DOI:
10.11648/j.plm.20250901.12
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Abstract: Background: Cadmium-induced reproductive toxicity significantly threatens male fertility, primarily through oxidative stress and alterations in testicular proteins. Objective: This study investigates omega-3 fatty acids as a potential therapeutic strategy to counteract cadmium-induced testicular damage. Methods Adult male Wistar rats were exposed to cadmium chloride, followed by oral omega-3 fatty acid supplementation. Testicular tissues were analyzed for oxidative stress markers (malondialdehyde, MDA), antioxidant enzyme activities (Superoxide dismutase (SOD), catalase (CAT), gluthanione peroxidase (GPx), and key reproductive proteins (acrosin, clusterin, osteopontin, annexin-A2, kallikrein-1) using) enzyme linked immunoassay (ELISA and spectrophotometry. Data were analyzed using appropriate statistical tools. Results: Omega-3 supplementation significantly (p < 0.05) reduced MDA levels, restored antioxidant enzyme activities, and preserved testicular protein integrity. Proteomic analysis revealed modulation of proteins involved in oxidative stress response, apoptosis, and spermatogenesis. Conclusion: These findings suggest that omega-3 fatty acids may serve as a promising therapeutic agent for mitigating cadmium-induced reproductive toxicity and preserving male fertility. Incorporating omega-3 into dietary interventions may offer an effective strategy against heavy metal-induced testicular damage.
Abstract: Background: Cadmium-induced reproductive toxicity significantly threatens male fertility, primarily through oxidative stress and alterations in testicular proteins. Objective: This study investigates omega-3 fatty acids as a potential therapeutic strategy to counteract cadmium-induced testicular damage. Methods Adult male Wistar rats were exposed t...
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