β-Lapachone protects against doxorubicin-induced nephrotoxicity via NAD+/AMPK/NF-kB in mice

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 392; no. 5; pp. 633 - 640
• Main Authors: Sanajou, Davoud, Nazari Soltan Ahmad, Saeed, Hosseini, Vahid, Kalantary-Charvadeh, Ashkan, Marandi, Yasser, Roshangar, Leila, Bahrambeigi, Saman, Mesgari-Abbasi, Mehran
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2019; Springer Nature B.V
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Antibiotics, Antineoplastic - adverse effects; Biomedical and Life Sciences; Biomedicine; Cancer; Creatinine; Cystatin C; Cytokines - genetics; Doxorubicin; Doxorubicin - adverse effects; Histopathology; IL-1β; Interleukin 6; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney Diseases - chemically induced; Kidney Diseases - drug therapy; Kidney Diseases - metabolism; Kidney Diseases - pathology; Kidneys; Lapachone; Mice; Mice, Inbred C57BL; NAD; NAD - metabolism; NADH; Naphthoquinones - pharmacology; Naphthoquinones - therapeutic use; Neurosciences; NF-kappa B - metabolism; NF-κB protein; Nicotinamide adenine dinucleotide; Nitric oxide; Nitric-oxide synthase; Original Article; Oxidative stress; Pharmacology/Toxicology; Protective Agents - pharmacology; Protective Agents - therapeutic use; Rodents; Serum levels; Signal Transduction - drug effects; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Urea; NAD; NADH ratio; β-Lapachone; Doxorubicin; Nephrotoxicity; NAD+/NADH ratio
• ISSN: 0028-1298; 1432-1912; 1432-1912
• DOI: 10.1007/s00210-019-01619-0

β-Lapachone (B-LAP) is a natural naphtaquinone with established anti-oxidative stress and anti-cancer activities. We aimed to investigate B-LAP protective potential against doxorubicin (DOX)-induced nephrotoxicity in mice. The mice received an oral dose of B-LAP followed by a single intraperitoneal injection of 20 mg/kg DOX a day later. They were then treated for 4 days with 1.25 mg/kg, 2.5 mg/kg, and 5 mg/kg doses of B-LAP. Renal levels of NAD + /NADH ratios, p-AMPKα, p-NF-κB p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) along with renal expressions of TNF-α, IL-1β, and IL-6 were examined. Serum levels of kidney function markers as well as renal histopathology were also investigated. In addition to increasing the activities of p-AMPKα, B-LAP elevated NAD + /NADH ratios in the kidneys and decreased the renal levels of nuclear p-NF-κB and its correspondent downstream effectors TNF-α, IL-1β, IL-6, and iNOS in the kidneys. Also, B-LAP effectively ameliorated renal architectural changes and attenuated serum levels of urea, creatinine, and cystatin C. Collectively, these findings suggest the protective actions of B-LAP against DOX-induced nephrotoxicity in mice.