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

Morsi, Ahmed A.; Ahmed, Sahar Bastawy; Saleh, Neveen M; Abd El-Aal, Rania Awad; El Malah, Tamer; Elsayed, Asmaa M.

doi:10.21608/jcbr.2021.74096.1207

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

Document Type : Original Article

Authors

¹ Department of Histology and Cell Biology, Faculty of Medicine, Fayoum University, Fayoum, Egypt

² Division of Biochemistry, National Organization for Drug Control and Research (NODCAR), Giza, Egypt

³ Microbiology Department, National Organization for Drug Control and Research (NODCAR), 14281, Giza, Egypt

⁴ Developmental Pharmacology Department, National Organization for Drug Control and Research (NODCAR), Giza, Egypt

⁵ Photochemistry Department, Chemical Industries Research Division, National Research Centre

10.21608/jcbr.2021.74096.1207

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.

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