metabolite from kidney

12-Ketodeoxycholic acid, a bile acid and kidney metabolite, serves as a detectable marker for kidney injury [1].

DCVC inhibits pathogen-stimulated TNF-α in human extra placental membranes in vitro.Target: TNF-αin vitro: DCVC inhibits pathogen stimulated cytokine release from tissue punch cultures. DCVC (5-50 μM) significantly inhibits LTA-, LPS-, and GBS-stimulated cytokine release from tissue cultures as early as 4 h (P ≤ 0.05). In contrast, TCA (up to 500 μM) does not inhibit LTA-stimulated cytokine release from tissue punches. DCVC effects on LTA-stimulated and LPS-stimulated TNF-α release from tissue punch cultures of extraplacental membranes. DCVC effects on GBS-stimulated release of pro-inflammatory cytokines from extraplacental membranes in transwell cultures. [1]. Boldenow E, et al. The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine but not trichloroacetate inhibits pathogen-stimulated TNF-α in human extraplacental membranes in vitro. Reprod Toxicol. 2015 Apr;52:1-6. [2]. Lash LH, et al. Multigenerational study of chemically induced cytotoxicity and proliferation in cultures of human proximal tubular cells. Int J Mol Sci. 2014 Nov 18;15(11):21348-65. [3]. Yoo HS, et al. Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: kidney effects. J Toxicol Environ Health A. 2015;78(1):32-49.

Dehydro warfarin, a metabolite of (±)-warfarin, is formed by rat liver microsomes from (±)-warfarin.

Dolutegravir O-β-D-glucuronide is a metabolite of the HIV integrase inhibitor dolutegravir .1It is formed from dolutegravir primarily by the UDP-glucuronosyltransferase (UGT) isoform UGT1A1in vivobut is also metabolized by UGT1A9 in human liver and kidney microsomes and UGT1A3 in human intestinal microsomes.2,1 1.Liu, S.N., Lu, J.B., Watson, C.J.W., et al.Mechanistic assessment of extrahepatic contributions to glucuronidation of integrase strand transfer inhibitorsDrug Metab. Dispos.47(5)535-544(2019) 2.Reese, M.J., Savina, P.M., Generaux, G.T., et al.In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitorDrug Metab. Dispos.41(2)353-361(2013)

Potassium 1H-indol-3-yl sulfate (Potassium 3-indoxyl sulfate) is an agonist for the human Aryl Hydrocarbon Receptor (AhR), a key regulator of immune-inflammatory conditions. A metabolite of tryptophan derived from dietary protein, it is produced by intestinal bacteria and metabolized in the liver. In chronic kidney disease patients with impaired renal function, it accumulates in serum as a uremic toxin, inducing oxidative stress and accelerating disease progression. At 250 μM, it activates NF-Κb, promoting TGF-β1 and Smad3 expression in rat proximal tubular cells, which is associated with profibrotic activity.

Phenyl sulfate is a gut microbiota-derived metabolite of tyrosine and a recognized uremic toxin. At a concentration of 30 µM, phenyl sulfate reduces the survival of differentiated human urinary podocyte-like epithelial cells (HUPECs), decreases intracellular glutathione (GSH) levels, and induces mitochondrial dysfunction. In a db/db mouse model of diabetes, phenyl sulfate administered at a dose of 50 mg/kg induces podocyte damage and albuminuria. Elevated plasma levels of phenyl sulfate are correlated with the progression of albuminuria in patients suffering from diabetic kidney disease, highlighting its role as a biomarker and potential therapeutic target.

Lentztrehalose A, a disaccharide microbial metabolite identified in Lentzea, exhibits a range of biological activities. This compound specifically inhibits M. smegmatis trehalase—an enzyme involved in trehalose metabolism—more effectively than trehalase from porcine kidney, with IC50 values of 0.67 mM and >20 mM, respectively. Additionally, Lentztrehalose A at a concentration of 100 mM promotes autophagy in MeWo melanoma and OVK18 ovarian cancer cells. When administered at 50 mg/kg daily, it enhances survival rates and impedes tumor growth in a Sarcoma 180 murine sarcoma model.

Lentztrehalose B, a microbial disaccharide metabolite isolated from Lentzea, exhibits a range of biological activities. At a concentration of 100 µM, it demonstrates antioxidant properties in an oxygen radical absorbance capacity (ORAC) assay. Furthermore, Lentztrehalose B at 10 mM inhibits porcine kidney trehalase, an enzyme involved in trehalose metabolism. Additionally, it induces autophagy in MeWo melanoma and OVK18 ovarian cancer cells when applied at 100 mM.