الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 148 |  |  |
| | | from | 148 | | |
Abstract
Diabetes mellitus has become one of the most serious and prevalent chronic diseases in recent years leading to life-threatening, costly, and disabling complications. Diabetes is related to male reproductive dysfunctions such as testicular and erectile dysfunctions. Male infertility is 5–10 times more common in diabetic patients than in healthy people and approximately half of diabetic patients suffer from some form of reproductive dysfunction.
Alogliptin, a DPP-4 inhibitor, and liraglutide, a GLP-1 receptor agonist, are used for T2DM management. Both showed beneficial effects in several experimental and clinical work such as antioxidant, anti-inflammatory, and antiapoptotic effects.
In the present study, we aimed to demonstrate the role of incretin-based therapies on diabetic testicular dysfunction and to investigate whether DPP-4i or GLP-1 RA can produce superior protective effects against diabetic-testicular dysfunction as a comparative study. Moreover, this study aimed to find out possible signaling pathways underlying their possible protective effects.
Adult male Wistar rats were initially divided into two groups, control and NA/STZ-induced
diabetic rats. one week later after induction of T2DM, either the control or diabetic groups were further subdivided into groups each consisting of 8 rats and were given the respective drug regimen for 8 weeks. Control group received vehicle alone, ALO group received alogliptin alone (20 mg/kg/day, P.O), LIRA group received liraglutide alone (0.2 mg/kg/day, S.C), DM group: diabetic rats received vehicle alone, DM+ALO: diabetic rats received alogliptin (20 mg/kg/day, P.O) and DM+LIRA: diabetic rats received liraglutide (0.2 mg/kg/day, S.C).
After 8 weeks of administration of either alogliptin or liraglutide blood, epididymides and testes were collected for:
• Assessment of sperm counts and motility
• Assessment of serum levels of testosterone and LH
• Measurement of testicular oxidative stress parameters (lipid peroxidation (MDA), reduced GSH levels and SOD activity)
• Evaluation of the testicular protein expression of the inflammatory markers (TLR-4, NF-κB and TNF-α) and the apoptotic marker, cleaved caspase-3.
• Assessment of the histopathological changes of the testes.
Our results suggested that both ALO and LIRA have protective effects against testicular dysfunction induced by diabetes over 8 weeks. They improved sperm counts, sperm motility and the hypothalamic-pituitary-testicular axis. They also attenuated the elevated lipid peroxidation and improved antioxidant capacity by increasing testicular GSH level and SOD activity. Furthermore, they attenuated the inflammation process by downregulation of protein expression of the inflammatory markers (TLR4, NF-κB, TNF-α). Moreover, they attenuated diabetes-induced testicular apoptosis by reduction of testicular protein expression of apoptotic marker, cleaved caspase-3. All these findings were consistent with the histopathological results which showed that both drugs improved testicular damage induced by diabetes. Regarding the comparison between ALO and LIRA, LIRA showed superiority in improving sperm quality, higher serum levels of testosterone and LH, and better antioxidant and anti-inflammatory properties which are all reflected in the histopathological changes.