The contribution of testosterone to the nephrotoxic effects of 1,2-dichloropropane (DCP) was assessed by a series of castration and sex hormone replacement experiments on Wistar rats. The nephrotoxic action of DCP was evaluated by measuring the accumulation of organic anion and release of aspartate aminotransferase into the incubation medium using a renal cortical slice model. Our data show that sex, castration, and testosterone pretreatment are factors that influence the effect of DCP on renal cortical slices of rats Males appear to be more sensitive to nephrotoxic effects of DCP than females, male castration prevents the nephrotoxic effects of DCP, and pretreatment of females and castrated males with testosterone increases the susceptibility to DCP. In this study an attempt was made to evaluate the role of sex differences in the expression of enzymes participating in Phase I and Phase II detoxication reactions in order to explain the differences in sensitivity of the two genders to the nephrotoxic action of DCP. Our results implicate gender-specific expression of cytochrome P-450 in the kidneys as a predominant factor that determines the different susceptibilities of male and female rats to the nephrotoxic effect of DCP. We propose that the oxidation of DCP by CYP IIE1 is the first saturable and limiting step in the metabolic activation of DCP to nephrotoxic metabolites. It appears that, despite the fact that the nephrotoxic effect of DCP is determined mainly by its cysteine-conjugated metabolites, gluthathione (GSH) content and glutathione S-transferase (GST) activity in kidney are not directly related to increased androgen-related susceptibility to DCP.(ABSTRACT TRUNCATED AT 250 WORDS)
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.3109/08860229509037616 | DOI Listing |
Heliyon
January 2025
Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi City, Taiwan.
Bladder cancer ranks as the 9th most common type of cancer worldwide. Approximately 70 % of bladder cancers are diagnosed as non-muscle invasive, and they are treated with transurethral resection followed by intravesical therapy. Doxorubicin is one of the effective cytotoxic drugs used in intravesical and systemic therapy, but its cardiotoxicity and nephrotoxicity limit therapeutic dosages.
View Article and Find Full Text PDFProstate
January 2025
Department of Urology, Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey.
Background: Metastatic castration resistance prostate cancer (mCRPC) is a challenging disease with a significant burden of mortality and morbidity. Most of the patients attain resistance to the available treatments, necessitating further novel therapies in this clinical setting. Actinium 225 (Ac) prostate-specific membrane antigen (PSMA) radioligand therapy has emerged as a promising option and has been utilized for the last decade.
View Article and Find Full Text PDFAust J Rural Health
February 2025
Murtupuni Centre for Rural and Remote Health, James Cook University, Townsville, Queensland, Australia.
Objective: This study aimed to explore the perspectives of healthcare professionals on the utility of sick day management plans for people with chronic kidney disease (CKD) in remote communities and collaboratively design a sick day management plan resource.
Design: This qualitative study utilised two phases of data collection: preliminary observational data and semi-structured interviews. The research design and analysis were guided by the normalisation process theory (NPT) framework, tailored for complex interventions in healthcare.
Microb Pathog
January 2025
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan. Electronic address:
Multi-drug resistant (MDR) Acinetobacter baumannii accounts for high mortality rates in hospital-acquired infections. Colistin is the last resort treatment despite nephrotoxic effects and the emergence of colistin resistant A. baumannii.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!