title: Perivascular cell protection in vivo and increased cell survival in vitro by the antihypertensive agent carvedilol following radiation.
abstract: Carvedilol, an antihypertensive drug with activity on adrenoceptors as well as on calcium channel activity, has recently been introduced. In the present study we investigated whether carvedilol interacts with the cytotoxicity induced by irradiation in vitro as well as in vivo. A daily injection of carvedilol in clinically relevant concentrations (3 mg/kg subcutaneously), 4 days before and 3 days after a single radiation dose of 20 Gy significantly decreased the inflammatory reaction in the rat lung, evaluated as number of inflammatory cells in the perivascular area. The density of mast cells was also slightly reduced. In vitro studies revealed that carvedilol caused different radio-protective effects, dependent on dose (1-7 Gy) used and cell line studied. The effects were especially pronounced in a malignant mesothelioma cell line (P-31), and somewhat less evident in a prostatic carcinoma cell line (PC-3). No significant effect was seen in a highly radiosensitive small cell lung cancer cell line (U-1690). Thus, carvedilol may under some circumstances interact with radiation-induced tissue reactions, most probably by a direct interaction at the cellular level. The specific explanation to the differences in sensitivity to carvedilol remains to be evaluated, but the known antioxidative properties and/or scavenging of free radicals of carvedilol may be a plausible mechanism of action. Secondary induced alterations in inflammatory response may also be considered. It is suggested that a potential interaction between drugs such as carvedilol and irradiation should be considered for clinical practice.
authors.affiliation: Department of Oncology, Umeå University Hospital, Sweden.
authors.forename: O E
authors.initials: OE
authors.lastname: Jonsson
authors.forename: L
authors.initials: L
authors.lastname: Bjermer
authors.forename: J
authors.initials: J
authors.lastname: Denekamp
authors.forename: K
authors.initials: K
authors.lastname: Grankvist
authors.forename: R
authors.initials: R
authors.lastname: Henriksson
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002470:Cell Survival; D004353:Drug Evaluation, Preclinical; D008297:Male; D011412:Propanolamines / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D017564:Radiation Pneumonitis / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D011837:Radiation-Protective Agents; D000077261:Carvedilol