The combined effect of furosemide and propranolol on GSH homeostasis in ACHN renal cells.
OBJECTIVE
Propranolol, a beta-adrenergic blocker, is used in the treatment of a large number of cardiovascular diseases such as hypertension and arrhythmias. Propranolol, in combination with furosemide, is used to treat hypertensive disorders although their side effect profile is not very obvious. In present study, the effects of the drugs furosemide and propranolol were in corporately investigated both on glutathione homeostasis and their antioxidant effect on ACHN cells.


METHODS
The cytoxicities and antioxidant effects of these two clinically important drugs on human kidney cell lines were evaluated using MTT following by the determination of glutathione reductase (GR) and glutathione peroxidase (GPx) activities and measuring the level of reduced glutathione (GSH).


RESULTS
Propranolol induced a significant cytotoxic effect at 100 µM, while furosemide was cytotoxic at doses of 250 and 1000 µg/ml. A slight increase in GPx and GR activities and GSH level was observed with propranolol and furosemide treatment alone, while the two drugs together caused a significant increase in GPx and GR activities (35% and 42%, respectively) and GSH content (35%) in ACHN cell lysates (p < 0.05).


CONCLUSIONS
Our results demonstrate that although high doses of furosemide and propranolol are cytotoxic, co-administration of low doses may improve the antioxidant defense in patients undergoing treatment with these two important drugs.
Reproductive Biology Department, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences , Shiraz , Iran .
Fatemeh
F
Zal
Raheleh
R
Taheri
Fatemeh
F
Khademi
Ehsan
E
Keshavarz
Sadegh
S
Rajabi
Zohreh
Z
Mostafavi-Pour
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000633:toxicity; D002460:Cell Line; D004232:Diuretics / Q000008:administration & dosage / Q000633:toxicity; D004359:Drug Therapy, Combination; D005347:Fibroblasts / Q000187:drug effects; D005665:Furosemide / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000187:drug effects*; D015394:Molecular Structure; D011433:Propranolol / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
D000319:Adrenergic beta-Antagonists; D004232:Diuretics; D005665:Furosemide; D011433:Propranolol; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione
ACHN cell line; furosemide; glutathione homeostasis; propranolol