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Protective effect of dipeptidyl peptidase-4 inhibitors in testicular torsion/detorsion in rats: a possible role of HIF-1α and nitric oxide.
Naunyn Schmiedebergs Arch Pharmacol. 2020 04; 393(4):603-614.NS

Abstract

Spermatic cord torsion is a serious and common urologic emergency. It requires early diagnosis for prevention of subfertility and testicular necrosis. Vildagliptin and sitagliptin are anti-diabetic drugs of the dipeptidyl peptidase-4 (DPP-4) inhibitors that have a protective role against cerebral ischemic stroke and cardiac ischemia reperfusion. This study aimed to investigate the role and mechanism of action of vildagliptin and sitagliptin in a model of testicular ischemia/reperfusion injury by testicular torsion/detorsion (T/D). Testicular T/D was done and vildagliptin and sitagliptin were administered either alone or in combination with nitric oxide synthase (NOS) inhibitor. Serum total cholesterol and testosterone were measured, while in testicular tissue testosterone, malondialdehyde (MDA) level, total antioxidant capacity (TAC), nitric oxide level, caspase-3, superoxide dismutase (SOD), hypoxia-inducible factor-1α (HIF-1α), tumor necrosis factor-α (TNF-α) and endothelial NOS (eNOS), and inducible NOS (iNOS) and neuronal NOS (nNOS) were measured. Histopathology of testicular tissue was done. Vildagliptin and sitagliptin increased serum testosterone, expression, and activity of SOD and testicular TAC. It also reduced total serum cholesterol, testicular MDA, caspase-3, HIF-1α, TNF-α, and expression of eNOS, iNOS, and nNOS. Vildagliptin and sitagliptin also improved histopathological picture of testicular tissue. NOS inhibitor produced similar result to DDP-4 inhibitors; however, its co-administration augmented the effect of vildagliptin and sitagliptin on these parameters. DPP-4 inhibitors, vildagliptin, and sitagliptin were protective against testicular T/D-induced injury mostly by anti-oxidative stress, and anti-apoptotic and anti-inflammatory actions that was augmented by NOS inhibition with a possible role for HIF-1α expression.

Authors+Show Affiliations

Department of Pharmacology, Minia University, Minia, 61111, Egypt.Department of Pharmacology, Minia University, Minia, 61111, Egypt. roshdyremon@yahoo.com. Department of Pharmacology, Deraya University, New Minia City, Egypt. roshdyremon@yahoo.com.Department of Biochemistry, Deraya University, New Minia City, Egypt.Department of Pathology, Minia University, Minia, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31773182

Citation

Abdelzaher, Walaa Yehia, et al. "Protective Effect of Dipeptidyl Peptidase-4 Inhibitors in Testicular Torsion/detorsion in Rats: a Possible Role of HIF-1α and Nitric Oxide." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 393, no. 4, 2020, pp. 603-614.
Abdelzaher WY, Rofaeil RR, Ali DME, et al. Protective effect of dipeptidyl peptidase-4 inhibitors in testicular torsion/detorsion in rats: a possible role of HIF-1α and nitric oxide. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(4):603-614.
Abdelzaher, W. Y., Rofaeil, R. R., Ali, D. M. E., & Attya, M. E. (2020). Protective effect of dipeptidyl peptidase-4 inhibitors in testicular torsion/detorsion in rats: a possible role of HIF-1α and nitric oxide. Naunyn-Schmiedeberg's Archives of Pharmacology, 393(4), 603-614. https://doi.org/10.1007/s00210-019-01765-5
Abdelzaher WY, et al. Protective Effect of Dipeptidyl Peptidase-4 Inhibitors in Testicular Torsion/detorsion in Rats: a Possible Role of HIF-1α and Nitric Oxide. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(4):603-614. PubMed PMID: 31773182.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effect of dipeptidyl peptidase-4 inhibitors in testicular torsion/detorsion in rats: a possible role of HIF-1α and nitric oxide. AU - Abdelzaher,Walaa Yehia, AU - Rofaeil,Remon Roshdy, AU - Ali,Doaa Mohamed Elroby, AU - Attya,Mina Ezzat, Y1 - 2019/11/26/ PY - 2019/07/21/received PY - 2019/11/08/accepted PY - 2019/11/28/pubmed PY - 2021/2/4/medline PY - 2019/11/28/entrez KW - Hypoxia-inducible factor-1α KW - Nitric oxide synthase KW - Sitagliptin KW - Testicular torsion/detorsion KW - Vildagliptin SP - 603 EP - 614 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 393 IS - 4 N2 - Spermatic cord torsion is a serious and common urologic emergency. It requires early diagnosis for prevention of subfertility and testicular necrosis. Vildagliptin and sitagliptin are anti-diabetic drugs of the dipeptidyl peptidase-4 (DPP-4) inhibitors that have a protective role against cerebral ischemic stroke and cardiac ischemia reperfusion. This study aimed to investigate the role and mechanism of action of vildagliptin and sitagliptin in a model of testicular ischemia/reperfusion injury by testicular torsion/detorsion (T/D). Testicular T/D was done and vildagliptin and sitagliptin were administered either alone or in combination with nitric oxide synthase (NOS) inhibitor. Serum total cholesterol and testosterone were measured, while in testicular tissue testosterone, malondialdehyde (MDA) level, total antioxidant capacity (TAC), nitric oxide level, caspase-3, superoxide dismutase (SOD), hypoxia-inducible factor-1α (HIF-1α), tumor necrosis factor-α (TNF-α) and endothelial NOS (eNOS), and inducible NOS (iNOS) and neuronal NOS (nNOS) were measured. Histopathology of testicular tissue was done. Vildagliptin and sitagliptin increased serum testosterone, expression, and activity of SOD and testicular TAC. It also reduced total serum cholesterol, testicular MDA, caspase-3, HIF-1α, TNF-α, and expression of eNOS, iNOS, and nNOS. Vildagliptin and sitagliptin also improved histopathological picture of testicular tissue. NOS inhibitor produced similar result to DDP-4 inhibitors; however, its co-administration augmented the effect of vildagliptin and sitagliptin on these parameters. DPP-4 inhibitors, vildagliptin, and sitagliptin were protective against testicular T/D-induced injury mostly by anti-oxidative stress, and anti-apoptotic and anti-inflammatory actions that was augmented by NOS inhibition with a possible role for HIF-1α expression. SN - 1432-1912 UR - https://www.unboundmedicine.com/medline/citation/31773182/Protective_effect_of_dipeptidyl_peptidase_4_inhibitors_in_testicular_torsion/detorsion_in_rats:_a_possible_role_of_HIF_1α_and_nitric_oxide_ L2 - https://dx.doi.org/10.1007/s00210-019-01765-5 DB - PRIME DP - Unbound Medicine ER -