title: Dithiothreitol (DTT) rescues mitochondria from nitrofurantoin-induced mitotoxicity in rat.
abstract: Nitrofurantoin (N-(5-nitro-2-furfurylidine) 1-amino-hydantoine; NIT) is mainly used for the treatment of acute urinary tract infections. However, its administration can be associated with liver failure or cirrhosis. The aim of this study was to determine whether NIT is a mitochondrial toxicant, if so, what mechanism(s) is involved. The rat liver mitochondria were isolated and treated with different doses of NIT alone or in combination with a reagent of choice for protecting thiol groups, dithiothreitol (DTT). Several mitochondrial parameters, including succinate dehydrogenase activity (also called 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide assay), lipid peroxidation, superoxide dismutase activity, Reduced glutathione (GSH), and oxidized glutathione (GSSG), and GSSG (oxidized glutathione) levels were determined. The results from this study showed that simultaneous treatment of mitochondria with NIT and DTT significantly reduces the toxicity. Here, we provide evidence that mitochondrial dysfunction followed by depletion of reduced glutathione can be reversed by DTT administration.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, 71345-1583, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Omidi
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, 71345-1583, Iran.|Pharmaceutical Science Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Niknahad
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, 71345-1583, Iran.
authors.forename: Afshin
authors.initials: A
authors.lastname: Mohammadi-Bardbori
mesh_terms: D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002458:Cell Fractionation; D004229:Dithiothreitol / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009582:Nitrofurantoin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000892:Anti-Infective Agents, Urinary; D000975:Antioxidants; D009582:Nitrofurantoin; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D005978:Glutathione; D004229:Dithiothreitol
keywords: dithiothreitol; mitochondrial dysfunction; nitrofurantoin; oxidative stress