Journal article
Furosemide-induced genotoxicity and cytotoxicity in the hepatocytes, but weak genotoxicity in the bone marrow cells of mice
Fundamental & clinical pharmacology, Vol.26(3), pp.383-392
06/01/2012
DOI: 10.1111/j.1472-8206.2011.00927.x
PMID: 21352352
Abstract
Furosemide (FS) is a potent loop diuretic widely used in the management of fluid retention associated with cardiac, renal, and hepatic failure as well as for the treatment of hypertension. FS is a well-characterized and known hepatotoxin in both human and animal test systems. In this study, an attempt has been made to investigate the in vivo genotoxicity of FS at the hepatotoxic equivalent doses using the chromosomal aberration and the comet assay in the bone marrow cells of mice as the endpoints of evaluation. The animals were treated with FS at the doses of 2.5, 5, 10, 20, 40, and 80 mg/kg/body weight (bw) intraperitoneal (ip) for both single (24 h) and repeated dose (seven consecutive days) toxicity studies. FS toxicity in the hepatocytes was evaluated using the parameters, such as, alanine-/aspartate-aminotransferase (ALT/AST), single cell gel electrophoresis (comet), tissue histology, DNA fragmentation, and TUNEL assay as the endpoints. The results clearly demonstrate that FS produced toxic responses in the hepatocytes as evident from increased ALT/AST level, DNA damage, TUNEL positive cells and increased DNA fragmentation in mice in vivo. However, it is interesting that in bone marrow cells, FS did not induced structural chromosomal abberations, but produced mild DNA strand breaks as observed by the comet assay. So it is considered as weak genotoxic toward the bone marrow cells when compared to the hepatocytes of mice.
Details
- Title: Subtitle
- Furosemide-induced genotoxicity and cytotoxicity in the hepatocytes, but weak genotoxicity in the bone marrow cells of mice
- Creators
- Sambhu Charan Mondal - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160 062, India.Durga Nand Tripathi - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160 062, India.Ajit Vikram - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160 062, India.Poduri Ramarao - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160 062, India.Gopabandhu B. Jena - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160 062, India
- Resource Type
- Journal article
- Publication Details
- Fundamental & clinical pharmacology, Vol.26(3), pp.383-392
- Publisher
- Wiley
- DOI
- 10.1111/j.1472-8206.2011.00927.x
- PMID
- 21352352
- ISSN
- 0767-3981
- eISSN
- 1472-8206
- Number of pages
- 10
- Grant note
- National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar
- Language
- English
- Date published
- 06/01/2012
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984359849702771
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