Sitagliptin protects male albino rats with testicular ischaemia/reperfusion damage: Modulation of VCAM‐1 and VEGF‐A

Abstract

Twisting of the spermatic cord is considered a popular problem in the urological field, which may lead to testicular necrosis and male infertility. Sitagliptin, a glucose‐lowering agent, proved to have a vindicatory function in myocardial and renal ischaemia/reperfusion (I/R), but its role in testicular I/R has not yet been studied. The current work investigates its capability to recover the testicular I/R injury with shedding more light on the mechanism of its action. Four groups were used: sham, sham pretreated with sitagliptin, I/R and sitagliptin/I/R‐pretreated groups. The outcomes proved that I/R significantly decreased the serum testosterone, with a major increase in oxidative, inflammatory and nitrosative stress, along with a reduction in testicular vascular endothelial growth factor‐A level with marked germinal cell apoptosis. However, pretreatment with sitagliptin significantly reversed the profound testicular I/R damaging effects, on the basis of its antioxidant, anti‐inflammatory and anti‐apoptotic activities with the ability of recuperation of the testicular vascularity.

Design, Synthesis, Molecular Docking, Antiapoptotic and Caspase-3 Inhibition of New 1,2,3-Triazole/Bis-2(1H)-Quinolinone Hybrids

“…Additionally, the spermatogenesis process was significantly decreased if compared to the sham control group using Johnson's score, which confirmed the pathological damage in response to testicular I/R. These results match with the previously published reported results [59].…”

“…Multiple testicular specimens were stained by hematoxylin-eosin (ab245880, Abcam, Cambridge, MA, USA) using Cosentino's score [59] for semi-quantitation of pathological changes in different seminiferous tubules. By using Johnson's scoring system [59], the effect of ischemia on the spermatogenesis can be studied (See Supporting Materials).…”

Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion

“…Dipeptidyl peptidase-4 inhibitors are among the drugs studied for their potential use for new therapeutic purposes, a strategy referred to as drug repurposing or repositioning [ 9 ]. Recently, a large body of evidence has accumulated showing sitagliptin effectiveness in lessening tissue damage during intestinal [ 24 , 32 ], cardiac [ 23 , 33 ], cerebral [ 30 ], testicular [ 31 ] and renal [ 28 , 29 ] ischemia-reperfusion insult. Likewise, sitagliptin has reduced the histopathological signs of injury and decreased the serum activities of ALT and AST in animal models of hepatic IR [ 21 , 22 , 25 , 26 ], acting via mechanisms employing its anti-inflammatory and antioxidative properties.…”

“…Several experimental studies have demonstrated pleiotropic properties, including the antioxidative, anti-inflammatory and antiapoptotic action of sitagliptin [ 18 , 19 ], a well-tolerated DPP-4 inhibitor with moderate side effects [ 20 ]. Accordingly, we [ 21 , 22 ], as well as others [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], have shown that sitagliptin alleviates injury caused by IR procedure. However, the molecular background has not been fully elucidated.…”

The “Hitchhiker’s Guide to the Galaxy” of Endothelial Dysfunction Markers in Human Fertility

“…In vitro experiments suggested that the action of VEGF-A may be beneficial for some sperm motility parameters, in a concentration-dependent manner. Moreover, mouse models revealed that VEGF-A induces germ cells proliferation, promotes testicular regeneration by enhancement of the vascularization [196] and supports Leydig cell steroidogenesis [197]. Since both steroidogenesis and gametogenesis require an intact testicular microvascular compartment [193,197], it is not surprising that VEGF-A paracrine effects are required to maintain physiological testicular functions [197].…”