Milrinone ameliorates ischaemia‐reperfusion injury in experimental testicular torsion/detorsion rat model

Abstract

This experimental study aims to evaluate the efficacy of milrinone against ischaemia‐reperfusion injury due to testicular torsion/detorsion. Group 1 was defined as the control group. Testicular torsion/detorsion model was performed in Group 2. Group 3 had similar procedures to the rats in Group 2. In addition, 0.5 mg/kg of milrinone was administered intraperitoneally immediately after testicular torsion in Group 3. Histopathological examinations indicated a dramatic improvement in terms of inflammation, haemorrhage, oedema, congestion, Cosentino and Johnson scores in Group 3 compared to Group 2 (p = .037, p = .045, p = .018, p = .040, p = .033 and p = .03 respectively). Blood biochemical analyses, superoxide dismutase (SOD), glutathione peroxidase (GSH‐px) activity and total antioxidant status (TAS) levels increased significantly in Group 3 compared to Group 2 (p = .001, p = .024 and p < .001). Malondialdehyde (MDA), protein carbonyl (PC), interleukin 1beta (IL‐1beta), tumour necrosis factor‐alpha (TNF‐alpha) and total oxidant status (TOS) levels decreased in Group 3 compared to Group 2 (p = .001, p = .018, p < .001, p = .036 and p = .002 respectively). Tissue biochemical analyses determined an increase in SOD and GSH‐px activity in Group 3 compared to Group 2, while PC and MDA levels were reduced (p = .001, p < .001, p = .038 and p < .001 respectively). Milrinone attenuates ischaemia‐reperfusion injury that causes highly harmful effects due to testicular torsion/detorsion.

Conditioned medium of bone marrow mesenchymal stem cells improves sperm parameters and reduces histological alteration in rat testicular ischaemia/reperfusion model

“…Milrinone treatment reduced oedema and congestion. In addition to histopathology instances suggestive of inflammation in the above studies, inflammatory cytokines such as TNF‐α and IL‐1β were also elevated and reduced using milrinone (Kölükçü et al, 2021). Similarly, the present study showed that treatment with BMSC‐CM reduced oedema and congestion.…”

“…Considering that ROS and free radical synthesis induce apoptosis in Leydig and Sertoli cells, it was concluded that using different antioxidants and radical scavengers could mitigate the destructive effects of oxidative stress. For example, Kölükçü et al showed that milrinone led to increased activity of SOD and GSH‐Px, and decreased the levels of MDA, one of the products of cell membrane peroxidation (Kölükçü et al, 2021). The induced ischaemia/reperfusion also resulted in oedema and congestion in the interstitial testicular parts.…”

Testicular torsion in vivo models: Mechanisms and treatments

“…Milrinone (0.5 mg/kg, immediately after TT) administration, reduced inflammation ( p = 0.001), haemorrhage ( p < 0.001), edema ( p = 0.001), congestion ( p < 0.001), and increased Johnsen score ( p < 0.001) in treated animals’ testis, compared to non‐treated rats. Moreover, milrinone administration increased SOD, GPx, total antioxidant status ( p < 0.001) and decreased protein carbonyl, MDA, TNF‐α, IL‐1β, and TOS, compared to the non‐treated group 85 …”

“…Moreover, milrinone administration increased SOD, GPx, total antioxidant status (p < 0.001) and decreased protein carbonyl, MDA, TNF-α, IL-1β, and TOS, compared to the non-treated group. 85 Trapidil (5-methyl-7-diethylamino-triazolopyrimidine), an antianginal drug, is a growth factor inhibitor derived from PDE and platelet. 86 Using Trapidil in TT/TR-induced rats reduced ROS formation 86 and histopathological damages.…”

Involvement of Hypoxia-Inducible Factor 1-α in Experimental Testicular Ischemia and Reperfusion: Effects of Polydeoxyribonucleotide and Selenium

“…In order to counteract I/R effects, numerous therapeutic approaches acting on the different pathways have been tried, either with natural substances [ 25 , 26 , 27 ] or with nutraceuticals [ 28 , 29 , 30 ]. Among them, selenium (Se), a trace element able to lower oxidative stress [ 31 , 32 ], reduced MDA levels and increased superoxide dismutase (SOD) activity and ameliorated structural damages after testicular experimental I/R [ 33 ].…”