Biomaterial Database

N-acetylcysteine reduces amphotericin B deoxycholate nephrotoxicity and improves the outcome of murine cryptococcosis. 2020

Thais Furtado Ferreira Magalhães, and Marliete Carvalho Costa, and Rodrigo Assunção Holanda, and Gabriela Freitas Ferreira, and Vanessa Silva Dutra Carvalho, and Gustavo Jose Cota Freitas, and Noelly Queiroz Ribeiro, and Elúzia Castro Peres Emídio, and Paulo Henrique Fonseca Carmo, and Camila Bernardo de Brito, and Daniele Glória de Souza, and Cláudia Emanuela Viana Rocha, and Tatiane Alves Paixão, and Maria Aparecida de Resende-Stoianoff, and Daniel Assis Santos

Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Cryptococcosis is a life-threatening fungal infection, and its current treatment is toxic and subject to resistance. Drug repurposing represents an interesting approach to find drugs to reduce the toxicity of antifungals. In this study, we evaluated the combination of N-acetylcysteine (NAC) with amphotericin B (AMB) for the treatment of cryptococcosis. We examined the effects of NAC on fungal morphophysiology and on the macrophage fungicidal activity 3 and 24 hours post inoculation. The therapeutic effects of NAC combination with AMB were investigated in a murine model with daily treatments regimens. NAC alone reduced the oxidative burst generated by AMB in yeast cells, but did not inhibit fungal growth. The combination NAC + AMB decreased capsule size, zeta potential, superoxide dismutase activity and lipid peroxidation. In macrophage assays, NAC + AMB did not influence the phagocytosis, but induced fungal killing with different levels of oxidative bursts when compared to AMB alone: there was an increased reactive oxygen species (ROS) after 3 hours and reduced levels after 24 hours. By contrast, ROS remained elevated when AMB was tested alone, demonstrating that NAC reduced AMB oxidative effects without influencing its antifungal activity. Uninfected mice treated with NAC + AMB had lower concentrations of serum creatinine and glutamate-pyruvate transaminase in comparison to AMB. The combination of NAC + AMB was far better than AMB alone in increasing survival and reducing morbidity in murine-induced cryptococcosis, leading to reduced fungal burden in lungs and brain and also lower concentrations of pro-inflammatory cytokines in the lungs. In conclusion, NAC + AMB may represent an alternative adjuvant for the treatment of cryptococcosis.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008826	Microbial Sensitivity Tests	Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).	Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D003404	Creatinine		Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D003453	Cryptococcosis	Fungal infection caused by genus CRYPTOCOCCUS.	C gattii Infection,C neoformans Infection,C. gattii Infection,C. neoformans Infection,Cryptococcus Infection,Cryptococcus Infections,Cryptococcus gattii Infection,Torulosis,Cryptococcus neoformans Infection,C gattii Infections,C neoformans Infections,C. gattii Infections,C. neoformans Infections,Cryptococcoses,Cryptococcus gattii Infections,Cryptococcus neoformans Infections,Infection, C gattii,Infection, C neoformans,Infection, C. gattii,Infection, C. neoformans,Infection, Cryptococcus,Infection, Cryptococcus gattii,Infection, Cryptococcus neoformans,Infections, C gattii,Infections, C. neoformans,Toruloses
D003454	Cryptococcus	A mitosporic Tremellales fungal genus whose species usually have a capsule and do not form pseudomycellium. Teleomorphs include Filobasidiella and Fidobasidium.	Torula
D003840	Deoxycholic Acid	A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent.	Deoxycholate,Desoxycholic Acid,Kybella,Choleic Acid,Deoxycholic Acid, 12beta-Isomer,Deoxycholic Acid, 3beta-Isomer,Deoxycholic Acid, 5alpha-Isomer,Deoxycholic Acid, Disodium Salt,Deoxycholic Acid, Magnesium (2:1) Salt,Deoxycholic Acid, Monoammonium Salt,Deoxycholic Acid, Monopotassium Salt,Deoxycholic Acid, Monosodium Salt,Deoxycholic Acid, Sodium Salt, 12beta-Isomer,Dihydroxycholanoic Acid,Lagodeoxycholic Acid,Sodium Deoxycholate,12beta-Isomer Deoxycholic Acid,3beta-Isomer Deoxycholic Acid,5alpha-Isomer Deoxycholic Acid,Deoxycholate, Sodium,Deoxycholic Acid, 12beta Isomer,Deoxycholic Acid, 3beta Isomer,Deoxycholic Acid, 5alpha Isomer