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1.
Pak J Pharm Sci ; 32(6): 2667-2671, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31969300

ABSTRACT

Hydrochlorothiazide (HCTZ) belongs to the thiazide diuretics family that is used for the treatment of hypertension. Enalapril is another drug that is used for the treatment of hypertension. Recently, both drugs were combined in a single medication called vaseretic that showed a strong synergistic effect against hypertension. The aim of this investigation is to examine genotoxicity of HCTZ/enalapril on chromosomal damage by measuring the frequency of sister-chromatid exchanges (SCEs) in cultured human lymphocytes. Findings showed that HCTZ (5µg/mL) significantly increased SCEs frequency (P<0.01) in cultured cells relative to the untreated cells. The levels of SCEs induced by Enalapril (10µg/mL) was similar to the level detected in the untreated cultures (P>0.05). Interestingly, SCEs induced by combined treatment were significantly lower than HCTZ alone (P<0.05). Thus, enalapril seems to protect lymphocytes from genotoxicity induced by HCTZ. Neither HCTZ nor enalapril treatment (alone or in combination) induced changes in the mitotic index and the proliferative index (P>0.05). In conclusion, HCTZ increased SCEs in cultured lymphocytes, and this increase is reduced by enalapril.


Subject(s)
Antihypertensive Agents/therapeutic use , Enalapril/pharmacology , Hydrochlorothiazide/toxicity , Lymphocytes/drug effects , Adult , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/toxicity , Chromosomes, Human/drug effects , Drug Synergism , Drug Therapy, Combination , Enalapril/administration & dosage , Enalapril/therapeutic use , Humans , Hydrochlorothiazide/administration & dosage , Hydrochlorothiazide/antagonists & inhibitors , Hydrochlorothiazide/therapeutic use , Hypertension/drug therapy , Male , Sister Chromatid Exchange/drug effects , Young Adult
2.
Drug Chem Toxicol ; 27(2): 169-78, 2004 May.
Article in English | MEDLINE | ID: mdl-15198076

ABSTRACT

The effects of trifluoperazine on the mutagenicity of cyclophosphamide were examined in the progenies of Drosophila melanogaster males injected with 2 microliters of 5.0 mM cyclophosphamide and/or 0.1 mM trifluoperazine. The Muller-5 method was used to study the induction of sex-linked recessive lethals in five successive broods representing the different stages of spermatogenesis. Results should that both cyclophosphamide and trifluoperazine were proportionally toxic to the injected males. While cyclophosphamide was less toxic than trifluoperazine, it increased the frequencies of induced complete and mosaic lethals significantly (5% level) in all stages of spermatogenesis contrary to trifluoperazine which was non mutagenic and had only an additive effect over the toxicity of cyclophosphamide. The sizes of the mutated gonad tissue in the F1 mosaic female progenies of the males treated with cyclophosphamide alone ranged from 14% to 17% and of those treated with cyclophosphamide in association with trifluoperazine varied between 18% and 19%. Both complete and mosaic sex-linked lethals induced by cyclophosphamide treatments alone and in association with trifluoperazine were detected in singles and clusters.


Subject(s)
Antipsychotic Agents/toxicity , Mosaicism/chemically induced , Mutagens/toxicity , Trifluoperazine/toxicity , Animals , Drosophila melanogaster , Female , Male , Spermatogenesis/drug effects
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