renal toxicity

Citric Acid Monohydrate is a tricarboxylic acid found in citrus fruits. Citric acid is used as an excipient in pharmaceutical preparations due to its antioxidant properties. It maintains stability of active ingredients and is used as a preservative.

Citric acid (Citro) is a weak organic tricarboxylic acid found in citrus fruits. Citric acid is a food additive and a natural preservative.

Bucetin (3-Hydroxy-p-butyrophenetidide) is a pharmaceutical drug that functions as an analgesic and antipyretic. It was withdrawn from use in 1986 due to renal toxicity.

Phenazopyridine hydrochloride (Pyridium) is used orally as a urinary tract analgesic. Side effects of phenazopyridine hydrochloride administration can include nausea, interference with the oxygen-carrying capacity of red blood cells (methemoglobinemia), hemolytic anemia as well as renal and hepatic toxicity. It is reasonably anticipated to be a human carcinogen.

Chlorazanil is a triazine-derived compound that functions as a novel, orally active, and non-toxic diuretic. Chlorazanil exerts its pharmacological effect by selectively blocking sodium and chloride ion reabsorption in the distal renal tubule, promoting diuresis and modulating electrolyte balance without inducing significant systemic toxicity, in addition, chlorazanil increases renal prostaglandin activity by increased prostaglandin synthesis,marking it as a valuable agent in renal physiology research and diuretic drug development.

Fluorofenidone (AKF-PD) attenuates the progression of renal interstitial fibrosis partly by suppressing NADPH oxidase and extracellular matrix (ECM) deposition via the PI3K/Akt signalling pathway. Fluorofenidone is an analogue of AMR69. Which displays equivalent lower toxicity, antifibrotic activity, and longer half-life.

NMDAR antagonist 5 (Compound A17) is a multi-target antagonist that acts on NMDAR and monoamine transporters (SERT, DAT, and NET). It demonstrates strong NMDAR antagonistic efficacy (IC50= 0.3 μM) and effective activity on monoamine transporters (SERT IC50= 1.1 μM, DAT IC50= 0.7 μM, NET IC50= 2.7 μM). NMDAR antagonist 5 exhibits high safety with low toxicity (hepatic and renal toxicity IC50> 100 μM; cardiac toxicity IC50= 24.5 μM). It has antidepressant properties and is useful for depression research.

TRPC4/5-IN-2 (Compound 12) is an orally active transient receptor potential (TRPC5) inhibitor with an IC50 value of 81 nM. This compound exhibits good biosafety and low hepatic and renal toxicity, making it a promising candidate for the treatment of chronic kidney disease (CKD).

rac-1,2-bis-Palmitoyl-3-chloropropanediol is a 3-monochloropropane-1,2-diol (3-MCPD) ester.1It has been found as a contaminant in edible olive oils, with the lowest and highest concentrations in extra virgin and olive pomace oils, respectively.rac-1,2-bis-Palmitoyl-3-chloropropanediol has also been found in cottonseed and palm oils, as well as in shortening.2It induces renal tubular necrosis and a decrease in spermatids, but no gross pathological changes, in mice.3 1.Hung, W.-C., Peng, G.-J., Tsai, W.-J., et al.Identification of 3-MCPD esters to verify the adulteration of extra virgin olive oilFood Addit. Contam. Part B Surveill.10(3)233-239(2017) 2.MacMahon, S., Begley, T.H., and Diachenko, G.W.Occurrence of 3-MCPD and glycidyl esters in edible oils in the United StatesFood Addit. Contam. Part A. Chem. Anal. Control Expo. Risk Assess.30(12)2081-2092(2013) 3.Liu, M., Gao, B.-Y., Qin, F., et al.Acute oral toxicity of 3-MCPD mono- and di-palmitic esters in Swiss mice and their cytotoxicity in NRK-52E rat kidney cellsFood Chem. Toxicol.50(10)3785-3791(2012)

3-Deazaneplanocin A (DZNep) is a dual inhibitor of histone methyltransferase (EZH2) and S-adenosylhomocysteine hydrolase (AHCY) with antipoxidative activity that inhibits hepatic, renal, peritoneal, and airway fibrosis by inducing proteasomal degradation of its targets and reducing toxicity in animal models.

OAT1/3-IN-2 (compound 8) is a dual inhibitor of OAT1 and OAT3, demonstrating potential protective effects against Cys-Hg toxicity in HEK-OAT1 cells (10 μM) and may safeguard renal function. This compound is useful for investigating mercury-induced nephrotoxicity [1].

OAT1/3-IN-1 (compound 7), a dual inhibitor of OAT1 and OAT3, mitigates Cys-Hg toxicity in HEK-OAT1 cells at 10 μM and offers potential kidney protection. This compound is used in the investigation of mercury-induced renal damage [1].

(±)9(10)-DiHOME, the diol derivative of (±)9(10)-EpOME—a cytochrome P450-derived epoxide of linoleic acid also known as leukotoxin—is formed through the action of soluble epoxide hydrolase (sEH) in neutrophils. It exhibits toxicity towards Sf21 cells expressing sEH as well as tolacZ-expressing control cells, differing from leukotoxin which only harms sEH-containing cells. Furthermore, combined exposure to 9(10)- and 12(13)-DiHOME leads to cell death in rabbit renal proximal tubule cells by disrupting mitochondrial respiration, and causes lung injury, respiratory distress, and mortality in mice, highlighting its role as a toxic lipid mediator. Specifically, 9(10)-DiHOME has been associated with acute respiratory distress syndrome (ARDS), a severe and often deadly complication in patients with major burns. Elevated levels of this compound have been detected in the bronchoalveolar lavage fluid (BALF) of women, but not men, with chronic obstructive pulmonary disease (COPD), and its levels are also increased in patients with allergic asthma, indicating its significance in respiratory conditions.

2,3-Dimercaptopropanesulfonate (DMPS) acts as a mercury chelator. It lowers renal mercury concentrations while elevating urinary mercury levels in both uninephrectomized and normal rats treated with mercuric chloride. In a mouse model of developmental toxicity induced by heavy metals, DMPS (administered at 180 or 360 mg/kg per day for four days) mitigates methylmercury chloride-induced increases in embryotoxicity and fetal and maternal mortality, while also preventing the reduction in fetal bone ossification when given to pregnant mice.