EVALUATION OF GENOTOXIC AND HISTOPATHOLOG1C EFFECTS OF THE TRICYCLIC ANTIDEPRESSANT DRUG: AMITRIPTYLINE IN MALE ALBINO MICE
Walaa Mohamed Radwan Ahmed;
Abstract
ABSTRACT
The Amitriptyline HCI (AT) antidepressant, utilized widely in Egypt, was studied to evaluate its toxicity in male mice. Animals were divided into a control (untreated) group and 3 orally treated groups according to the AT treatment schedule. The treatment schedule was as follow: {i ) low: lmg/kg for 30 days; (ii) medium: lmg/kg for 15 days followed by 2mg/kg for 15 days; and (iii) High: 1mg/kg for 10 days followed by 2mg/kg for the next 10 days and then
4mg/kg for the last 10 days. Toxicity evaluation was carried out using four main endpoints: Cytogenetic studies (chromosomal aberrations) using mice bone marrow and spermatocytes; sperm morphology and count abnormalities, biochemical changes in liver (enzymes) and histopathological changes in liver and testis sections. The results obtained were statistically analyzed using Chi-square, Mann-Whitney, ANOVA one-way analysis of variance and Duncan tests using software package SPSS version 18. The statistical analysis revealed that Amitriptyline treatment with the three treatment schedules have induced a significant increase in chromosome abnormalities in both somatic and germ cells. Moreover, mitotic index and meiotic activity decreased significantly as well. In addition, a significant increase in sperm head and tail abnormalities as well as a significant decrease in the total sperm cells count was observed in all AT treated groups. Biochemical studies on liver enzymes indicated a significant increase in their activity based on the analysis of sera obtained from high treated mice group. Results of the histopathological changes in liver and testis showed minimal changes in liver with low and medium treatment groups. On the other hand, sections of liver and testis showed significant histopathological changes in the high treatment group. The results of the current study showed that amitriptyline is a toxic agent for both somatic and germ cells and that this toxicity is dose dependent. Accordingly, AT should be administrated under special precautions and medical supervision.
Key Words:
Amitriptyline HCl 2) Genotoxicity 3) Somatic and germ cells 4) Histopathological changes in liver and in testis 5) Liver enzymes.
The Amitriptyline HCI (AT) antidepressant, utilized widely in Egypt, was studied to evaluate its toxicity in male mice. Animals were divided into a control (untreated) group and 3 orally treated groups according to the AT treatment schedule. The treatment schedule was as follow: {i ) low: lmg/kg for 30 days; (ii) medium: lmg/kg for 15 days followed by 2mg/kg for 15 days; and (iii) High: 1mg/kg for 10 days followed by 2mg/kg for the next 10 days and then
4mg/kg for the last 10 days. Toxicity evaluation was carried out using four main endpoints: Cytogenetic studies (chromosomal aberrations) using mice bone marrow and spermatocytes; sperm morphology and count abnormalities, biochemical changes in liver (enzymes) and histopathological changes in liver and testis sections. The results obtained were statistically analyzed using Chi-square, Mann-Whitney, ANOVA one-way analysis of variance and Duncan tests using software package SPSS version 18. The statistical analysis revealed that Amitriptyline treatment with the three treatment schedules have induced a significant increase in chromosome abnormalities in both somatic and germ cells. Moreover, mitotic index and meiotic activity decreased significantly as well. In addition, a significant increase in sperm head and tail abnormalities as well as a significant decrease in the total sperm cells count was observed in all AT treated groups. Biochemical studies on liver enzymes indicated a significant increase in their activity based on the analysis of sera obtained from high treated mice group. Results of the histopathological changes in liver and testis showed minimal changes in liver with low and medium treatment groups. On the other hand, sections of liver and testis showed significant histopathological changes in the high treatment group. The results of the current study showed that amitriptyline is a toxic agent for both somatic and germ cells and that this toxicity is dose dependent. Accordingly, AT should be administrated under special precautions and medical supervision.
Key Words:
Amitriptyline HCl 2) Genotoxicity 3) Somatic and germ cells 4) Histopathological changes in liver and in testis 5) Liver enzymes.
Other data
| Title | EVALUATION OF GENOTOXIC AND HISTOPATHOLOG1C EFFECTS OF THE TRICYCLIC ANTIDEPRESSANT DRUG: AMITRIPTYLINE IN MALE ALBINO MICE | Other Titles | تقييم التأثيرات السمية والنسيجية المرضية لمضاد الاكتئاب من نوع ثلاثي الحلقات ( الاميتربتيلين ) علي ذكور قئران التجارب البيضاء | Authors | Walaa Mohamed Radwan Ahmed | Issue Date | 2011 |
Attached Files
| File | Size | Format | |
|---|---|---|---|
| Walaa Mohamed Radwan Ahmed.pdf | 3.29 MB | Adobe PDF | View/Open |
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