Evaluation of cytotoxic action of antihistamines – desloratadine and loratadine – using bulls spermatozoa as a test object
Abstract
Antihistamines with active ingredients of loratadine and desloratadine are produced by Ukrainian pharmaceutical industry. According to the law, ther are assessed for their potential danger to human health and the environment, including alternative test objects. Evaluation has been carried out with regard to cytotoxic effect of pharmacological substances (loratadine and desloratadine) using the bull sperm suspension as test objects, standardized and highly sensitive to toxic substances. Sperm was divided into the control sample (dissolved by phosphate-buffered saline) and the investigated sample. Loratadine was added to phosphate-buffered saline in doses of 1/500 LD50 (12.3 mg), 1/100 LD50 (61.5 mg) and LD50 (6150 mg). Desloratadine doses were 1/500 LD50 (1.25 mg), 1/100 LD50 (6.25 mg) and LD50 (625 mg). Survival of spermatozoa was defined until termination of rectilinear forward movement in sperm intacted at +2…+5 °C. Respiratory activity (ex tempore) was defined in 1.0 ml thermostated cell (temperature of 38.5 °C) by polarography with the automatic registration of process flow by potentiometer; restorative activity was defined potentiometrically, using the open microelectrodes that were inserted in thermostated polarographic cell. Survival of spermatozoa in the sperm under the impact of loratadine in doses of 1/500 LD50 and 1/100 LD50 is respectively 136.0 ± 26.2 hours and 144.0 ± 19.6 hours. Adding LD50 dose of loratadine reduced survival to 112.0 ± 26.2 hours, which is lower than the control (160.0 ± 26.1 hours), respectively, by 10.0–15.0 and 30.0%. Loratadine reduces the respiratory activity of sperm: in the dose of 1/500 LD50 by 20.5%, in the dose of 1/100 LD50 – by 43.6%, and that of 100 LD50 – by 61.5% compared to the control. Restorative sperm activity under the impact of the loratadine reduced by 84.0% (dose of 1/500 LD50), 98.0% (dose of 1/100 LD50), 80.0% (dose LD50) compared to controls. The survival of spermatozoa in the sperm under desloratadine action in the dose of 1/500 LD50 is 144.0 ± 19.6 hours (10.0% reduction compared with the control – 152.0 ± 23.6 hours), in the dose of 1/100 LD50 – 136.0 ± 26.1 hours (15.0% reduction), in the dose of LD50 – 72.0 ± 19.6 hours (30.0% reduction). The intensity of oxygen consumption by sperm reduced by 16.2% when adding desloratadine in the dose of 1/500 LD50, by 38.8% in the dose of 1/100 LD50 and by 80.7% – in the dose of LD50, compared with the control. Inhibition of respiratory activity is accompanied by decreasing in the transport of protons and electrons from spermatozoa into the extracellular medium, that manifests decreasing of reconstructive activity when the dose of desloratadine is 1/500 LD50 (by 12.0%), 1/100 LD50 (by 40.0%) and LD50 (by 60,0%) compared with the control.References
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