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199589

Caspase-3 activities and androgen receptor expression in rats’ testis during the early biochemical and histopathological changes induced by a carcinogen, Diethylnitrosamine: role of probiotics and pyridazine derivatives

Article

Last updated: 22 Jan 2023

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-

Tags

Animal models in cancer therapy

Abstract

Background: Diethylnitrosamine (DENA) is a common environmental toxicant with  a well-known hepatocarcinogenic potential. Aim: The current study aimed to: 1) investigate the carcinogenic toxicity of DENA on the rats' testis, 2) to elucidate the role of caspase-3 activities and androgen receptors (AR) in this toxicity, and 3) to assess the effect of treatment with Lactobacillus casei (LAB) and 3-methylsulfanyl-4,6-diphenyl-pyridazine (MDP) on testicular tumorigenesis. Material and Methods: Sixty Sprague–Dawley albino rats were divided into 6 groups; control, DENA-alone, DENA+MDP, DENA+LAB, DENA+DOX (Doxorubicin) and DENA+DOX+MDP. In all experimental animals, DENA was injected intraperitoneal (i.p) (55 mg/kg) twice weekly for 6 weeks. MDP (10 mg/kg, ip), LAB (1.5 x 109 CFU/kg, oral) and DOX (10 mg/kg, ip) were administered twice weekly for the following 4 weeks. Serum testosterone, anti-mullerian hormone, alpha-fetoprotein, tumor necrosis factor, nitric oxide, glutathione peroxidase, and sperm analysis were determined. Histopathological evaluation of the testis was done. AR and caspase-3 activities were detected by immunohistochemistry. Result: The DENA-alone-treated animals showed disturbed biochemical assays and marked tubular degenerative changes, in addition to notable Leydig cell hyperplasia (LCH) in the histological findings. MDP, LAB, DOX reversed the biochemical changes with less extent in DOX treatment. No further improvement was noted in the tubular histoarchitecture in DOX-treated groups meanwhile, LAB treatment restored LCH with a partial effect in MDP treatment. Conclusion: DENA induced AR-immunopositive Leydig cell hyperplastic changes, in addition to spermatogenic cytotoxicity with increased tubular caspase-3 activities. LAB and MDP reversed biochemical changes and had a curative potential on the testis with a partial anti-proliferative effect for MDP.

DOI

10.21608/jcbr.2021.74096.1207

Keywords

androgen receptors, Caspase-3, Diethylnitrosamine, Lactobacillus casei, 3-Methylsulfanyl-4, 6-diphenyl-pyridazine, pyridazine derivatives, testis

Authors

First Name

Ahmed

Last Name

Morsi

MiddleName

A.

Affiliation

Department of Histology and Cell Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt

Email

ahmed_saqr4@yahoo.com

City

-

Orcid

-

First Name

Sahar

Last Name

Ahmed

MiddleName

Bastawy

Affiliation

Division of Biochemistry, National Organization for Drug Control and Research (NODCAR), Giza, Egypt

Email

saharelhalaby@yahoo.com

City

-

Orcid

-

First Name

Neveen

Last Name

Saleh

MiddleName

M

Affiliation

Microbiology Department, National Organization for Drug Control and Research (NODCAR), 14281, Giza, Egypt

Email

neveensaleh0@gmail.com

City

-

Orcid

-

First Name

Rania

Last Name

Abd El-Aal

MiddleName

Awad

Affiliation

Developmental Pharmacology Department, National Organization for Drug Control and Research (NODCAR), Giza, Egypt

Email

raniaawad350@yahoo.com

City

Cairo

Orcid

-

First Name

Tamer

Last Name

El Malah

MiddleName

-

Affiliation

Photochemistry Department, Chemical Industries Research Division, National Research Centre

Email

tmara_nrc3000@yahoo.com

City

Cairo

Orcid

-

First Name

Asmaa

Last Name

Elsayed

MiddleName

M.

Affiliation

Department of Histology and Cell Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt

Email

ams04@fayoum.edu.eg

City

-

Orcid

-

Volume

5

Article Issue

4

Related Issue

29244

Issue Date

2021-12-01

Receive Date

2021-04-27

Publish Date

2021-12-01

Page Start

39

Page End

57

Print ISSN

2682-261X

Online ISSN

2682-2628

Link

https://jcbr.journals.ekb.eg/article_199589.html

Detail API

https://jcbr.journals.ekb.eg/service?article_code=199589

Order

4

Type

Original Article

Type Code

885

Publication Type

Journal

Publication Title

International Journal of Cancer and Biomedical Research

Publication Link

https://jcbr.journals.ekb.eg/

MainTitle

-

Details

Type

Article

Created At

22 Jan 2023