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Is losartan a promising agent for the treatment of type 1 diabetes-induced testicular germ cell apoptosis in rats?

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Abstract

Background

Diabetes mellitus (DM) is common metabolic disease that poses a major risk to public health and fertility. Previous studies indicate that DM may cause male infertility by triggering oxidative stress and germ cell apoptosis in the testis. Due to the undesirable effects of known antidiabetic drugs, scientists have begun to investigate the use of alternative drugs to control infertility complications observed in men. In this context, present study aimed to investigate the possible antiapoptotic effect of losartan against DM-induced testicular germ cell apoptosis.

Methods and results

Expreimental DM model was induced by intraperitoneal injection of streptozocin (STZ, 55 mg/kg) to 28 rats, which were then randomly assigned to 4 groups; 1 mL saline solution was given to DM + saline group by oral gavage, 5 mg/kg/day oral losartan was given to DM + low-dose losartan, 20 mg/kg/day oral losartan was given to DM + mid-dose losartan and, 80 mg/kg/day oral losartan was given to DM + high-dose losartan group for 4 weeks. Bax, Bcl-2 and cleaved-Caspase 3 immunoexpression, terminal-deoxynucleotidyl transferase dutp nick end labeling (TUNEL), Annexin-V and Real Time PCR analyses performed to evaluate antiapoptotic effects of losartan on diabetic rats’ testis. In addition, biochemical analyzes carried out to evaluate change in oxidative stress.

Conclusion

The results showed that losartan may have dose-related antiapoptotic effects on rats’ testis via decreasing oxidative stress.

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Data availability

Data available on request from the authors.

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Acknowledgements

The experimental procedures on the animals in this study were performed in Ege University, Drug Research and Development and Pharmacokinetic Applications (ARGEFAR).

Funding

This study was supported by the Ege University Research Fund [grant number 16-TIP-092 (to Altuğ Yavaşoğlu)].

Author information

Authors and Affiliations

  1. Faculty of Medicine, Department of Histology and Embryology, Ege University, 35100, Izmir, Izmir, Turkey

    Aylin Buhur, Çevik Gürel, Gökçe Ceren Kuşçu, Fatih Oltulu, Ayşegül Uysal & Altuğ Yavaşoğlu

  2. Faculty of Medicine, Department of Histology and Embryology, Harran University, Sanliurfa, Turkey

    Çevik Gürel

  3. Faculty of Medicine, Department of Histology and Embryology, Muğla Sıtkı Kocman University, Muğla, Turkey

    Gürkan Yiğittürk

  4. Faculty of Science, Department of Biology, Ege University, Izmir, Turkey

    Nefise Ülkü Karabay Yavaşoğlu

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  1. Aylin Buhur
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Contributions

AY; AB and FO desinged to study. AB; ÇG and GCK performed the animal models and in vivo experiments. AB, AU and GCK performed histochemical and immunohistochemical staining. NUKY and ÇG performed real time-PCR analyses. GY; FO and AB performed Annexin V analyses. NUKY and GY performed biochemical analyses. AY; AB and ÇG performed sperm parameters evaluation. AY; NUKY; AU and FO performed statistical analyses. ÇG and GCK wrote manuscript and all authors reviewed manuscript.

Corresponding author

Correspondence to Çevik Gürel.

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Ethical approval

The protocol was approved by Ege University, Local Ethics Committee for Animal Experiments (Approval no: 2016-085).

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Buhur, A., Gürel, Ç., Kuşçu, G.C. et al. Is losartan a promising agent for the treatment of type 1 diabetes-induced testicular germ cell apoptosis in rats?. Mol Biol Rep 50, 2195–2205 (2023). https://doi.org/10.1007/s11033-022-08172-9

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