Exploring the Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Genitourinary Toxicities in Prostate Cancer Patients Undergoing Radiation Therapy: A Case Study and Discussion.

Radiation therapy is a common treatment modality offered to patients with localized prostate cancer. It can be associated with early radiation-induced toxicities including dysuria, nocturia, frequency, urgency, spasm, and, rarely, hematuria. Early toxicities usually resolve once the treatment period has ended. Chronic toxicities are less common, and rarely, patients may experience radiation-induced hemorrhagic cystitis and hematuria months or years after radiation. We herein describe the case of a 65-year-old man with a past medical history of type-2 diabetes mellitus who experienced hemorrhagic cystitis for months following his radiation therapy. The patient was on sodium-glucose cotransporter-2 inhibitor therapy (empagliflozin), which we highlight as a potential risk factor for hemorrhagic cystitis. After cessation of Jardiance and initiation of semaglutide (GLP-1 agonist), his urinary symptoms significantly improved. To the best of our knowledge, this is the first such case reported.

A novel reactive aldehyde species inhibitor prevents the deleterious effects of ethanol in an animal model of alcoholic liver disease.

BACKGROUND AND AIMS: Current treatment strategies for alcoholic liver disease (ALD) are limited by the lack of agents specifically targeting the metabolic breakdown products of ethanol. Reactive aldehyde species (RASP) inhibitors have been developed that have the capability to sequester these aldehyde byproducts, potentially limiting toxicity. The purpose of this study was to determine if the RASP inhibitor ADX-629 could target these metabolic breakdown products in a mouse model of ALD. METHODS AND RESULTS: A chronic/binge mouse model of ALD was used to determine the efficacy of ADX-629 treatment. Mice were fed an alcohol-containing (5 %) liquid or control diet for 10 days and treated by oral gavage with ADX-629 30 min prior to administering a bolus gavage of 31.5 % ethanol. Test groups included: Control - no ADX, Control + ADX, Ethanol - no ADX and Ethanol + ADX. Compared to ethanol-fed mice receiving sham treatment, ethanol mice treated with ADX-629 demonstrated significant decreases (p < 0.05) in liver acetaldehyde (AA), liver malondialdehyde-acetaldehyde (MAA), circulating anti-MAA antibody, liver/serum triglycerides (p < 0.01) levels, and overall fat accumulation in the liver as determined by Oil Red O and bodipy staining (p < 0.0001). Serum levels of pro-inflammatory cytokines IFN-γ and MCP-1 levels were decreased following ADX-629 treatment (p < 0.01). CONCLUSIONS: These findings demonstrate that the use of this unique RASP inhibitor (ADX-629) is effective in the treatment of ALD. Given the ubiquitous nature of aldehydes in the context of tissue inflammation and damage, ADX-629 and other RASP inhibitors may have additional applications in disease states.

Differential Effects of Whole Red Raspberry Polyphenols and Their Gut Metabolite Urolithin A on Neuroinflammation in BV-2 Microglia.

Whole red raspberry polyphenols (RRW), including ellagic acid, and their gut-derived metabolite, urolithin A (UroA), attenuate inflammation and confer health benefits. Although results from recent studies indicate that polyphenols and UroA also provide neuroprotective effects, these compounds differ in their bioavailability and may, therefore, have unique effects on limiting neuroinflammation. Accordingly, we aimed to compare the neuroprotective effects of RRW and UroA on BV-2 microglia under both 3 h and 12 and 24 h inflammatory conditions. In inflammation induced by lipopolysaccharide (LPS) and ATP stimulation after 3 h, RRW and UroA suppressed pro-inflammatory cytokine gene expression and regulated the JNK/c-Jun signaling pathway. UroA also reduced inducible nitric oxide synthase gene expression and promoted M2 microglial polarization. During inflammatory conditions induced by either 12 or 24 h stimulation with LPS, UroA-but not RRW-dampened pro-inflammatory cytokine gene expression and suppressed JNK/c-Jun signaling. Taken together, these results demonstrate that RRW and its gut-derived metabolite UroA differentially regulate neuroprotective responses in microglia during 3 h versus 12 and 24 h inflammatory conditions.