الفهرس 
Aim of the workOnly 14 pages are availabe for public view
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Abstract
The introduction of anti-retroviral drugs (ARVDs) changed the prognostic of HIV infection from a terminal to a chronic disease. There are various classes of ARVDs including nucleoside reverse transcriptase inhibitors (NRTIs), non nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors, chemokine receptor type 5 (CCR5) inhibitors and integrase inhibitors (INI).
Nevirapine (NVP) is a first-generation of NNRTIs, cheap and widely available around the world. NVP is commonly used as part of the highly active antiretroviral therapy (HAART) in resource-limited settings. Currently, it remains one of the most prescribed antiretroviral drugs in developing countries, to prevent vertical transmission (mother-to-child) when used in combination therapy.
This antiviral therapy is able to decrease the levels of HIV and improve the functioning of the immune system, but unfortunately, the prolonged use can cause several adverse effects as skin rash, hypersensitivity syndrome, and hepatotoxicity. Therefore, the aim of this work was to assess the toxic effects of NVP on the tissues (liver, kidney and testis) and to study its genotoxic and mutagenic effects on male adult albino rats.
They were divided into 4 equal groups (10/ each):
(A) Male negative control group: lifted without intervention to measure the basic parameters, with free access to food and water for 4 weeks.
(B) Male positive control group: each rat received 1ml/ day of corn oil by oral gavage for 4 weeks.
(C) NVP1 male treated group: each rat received the loading dose of NVP (3.6mg/ 200g) once daily for 14 day.
(D) NVP2 male treated group: each rat received the loading dose of NVP (3.6mg/ 200g) once daily for 14 day then received the maintenance dose of NVP (7.2mg/ 200g) once daily for another 14 day.
At the end of the period of the study, the rats were sacrificed and blood samples were obtained from the rats’ heart of each group to estimate the levels of serum urea, creatinine, alanine aminotransferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), total bilirubin, testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and to assess the genotoxic effect by comet assay.
Also, the livers, kidneys and testes were dissected and subjected to histopathological examination by light microscope.
The results of the present study can be summarized in the following data:
1- Biochemical finding:
In this study, NVP treated rats showed a highly significant increase in mean values of the serum AST, ALT, ALP and total bilirubin levels. At the same time, NVP treated rats showed a highly significant decrease in mean values of testosterone, FSH and LH levels. But, all studied groups showed no statistical significant regarding mean values of serum urea and creatinine levels.
2- Histopathological changes:
The biochemical findings are associated with histopathological changes in the hepatic tissues of NVP treated rats stained by hematoxylin and eosin stains. These changes were in the form of central vein congestion, fatty degenerations with singent ring appearance, hydropic degeneration in NVP1 treated rats which aggravated to severe portal and central venous congestion and major distortion of architecture with marked necrosis in NVP2 treated rats.
In the renal tissues stained by hematoxylin and eosin stains, there were no visible lesions when were comparable to the control groups.
In the testicular tissues stained by hematoxylin and eosin stains, the changes were degeneration of seminiferous tubules (ST), necrosis of spermatocytes and defoliation of many spermatocytes into lumen of the ST in NVP1 treated rats. These changes became more severe in NVP2 treated rats in the form of marked lose of testicular tissue architecture, extensive degeneration of ST, necrosis of spermatocytes and defoliation of many spermatocytes into lumen of the ST.
3- Comet findings:
Nevirapine treated rats showed significant increase in mean values of comet %, tail moment, DNA % in tail and tail length when compared to the controls. These changes indicated DNA damage of the whole blood cells of treated rats.
Conclusion
In conclusion, this study demonstrated that oral administration of nevirapine at human loading and maintenance doses in rats (3.6 mg/ 200g, 7.2 mg/ 200g) respectively produced biochemical changes on liver functions of male adult albino rats. These biochemical changes were associated with histopathological effects on their livers. Also, the same doses of NVP produced hormonal disruption effects in male rats. These disrupted effects were associated with histopathological damaging effects on testes. But, NVP did not disrupt renal histo-architecture or biochemical functioning of kidney. On the other hand, this current study demonstrated that human therapeutic dose of NVP induced genotoxic effects on whole blood cells of albino rats.