Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of contralateral injury after ipsilateral TT are not fully understood. In the presented study, we investigated the molecular and microscopic basis of ipsilateral and contralateral testicular injury following ipsilateral testicular torsion detorsion (T/D) and explored the possible protective role of vitamin D3. The biochemical analysis indicated that IR injury following T/D significantly decreased the activity of testicular glutathione peroxidase (GPx) enzyme, level of serum testosterone, serum inhibin B, and expression of testicular miRNA145, while increased the activity of testicular myeloperoxidase (MPO) enzyme, level of testicular malondialdehyde (MDA), level of serum antisperm-antibody (AsAb), and expression of ADAM-17. The histological and semen analysis revealed that torsion of the testis caused damages on different tissues in testis. Interestingly, administration of vitamin D3 prior to the IR injury reversed the deterioration effect of IR injury on the testicular tissues as indicated by biochemical and histological analysis which revealed normal appearance of the seminiferous tubules with an apparent decrease in collagen fiber deposition in both ipsilateral and contralateral testes. Our results revealed that the protective effect of vitamin D3 treatment could be attributed to target miRNA145 and ADAM17 protein. To further investigate these findings, we performed a detailed molecular modelling study in order to explore the binding affinity of vitamin D3 toward ADAM17 protein. Our results revealed that vitamin D3 has the ability to bind to the active site of ADAM17 protein via a set of hydrophobic and hydrophilic interactions with high docking score. In conclusion, this study highlights the protective pharmacological application of vitamin D3 to ameliorate the damages of testicular T/D on the testicular tissues via targeting miRNA145 and ADAM17 protein.

Background: Thioacetamide (TAA), a known industrial toxic agent, is extensively used in animal studies for induction of hepatic necrosis, fibrosis and cirrhosis, also reported to be nephrotoxic through induction of oxidative stress. Propolis, bee glue, is known by its antioxidant and anti-inflammatory properties. Aim of Study: This work aimed to evaluate the potential protective effect of propolis on TAA-induced hepatorenal damage and to evaluate the efficacy of Kidney Injury Molecuole-1 (KIM-1) in early detection of renal injury. Material and Methods: This study was performed on 24 adult male albino rats, divided into 3 groups; (I) Control group, (II) TAA-group (TAA was given in a dose of 50mg/kg /day intraperitoneally, 5 days/week for 2 weeks), (III) TAApropolis treated group (TAA was given in the same way as in TAA-group, propolis was given in a dose of 500mg/kg/day by gavage, 5 days/week for 2 weeks). All studied rats were subjected to determination of initial and final body weight, body weight percent change, absolute and relative liver and kidney weight, as well as assessment of hepatic function by serum Alanine Transaminase (ALT) and Aspartate Transaminase (AST), renal function by serum urea, creatinine and potassium (K+) level, with determination of renal tissue oxidative stress markers; Malondialdehyde (MDA) and Glutathione-S-Transferase (GST), inflammatory marker; Myeloperoxidase (MPO), renal tissue damage marker; Kidney Injury Molecule-1 (KIM-1). In addition, specimens of liver and kidney were taken and processed for light microscopic studies. Results: TAA induced hepatotoxic and nephrotoxic effect that was evident by the significantly increased serum ALT, AST, urea and creatinine, with significant decrease in serum K + level as well as significantly increased renal tissue MDA, GST, MPO and KIM-1 when compared with control group. Treatment with propolis caused significant reduction in serum ALT, AST, urea and creatinine, with significant elevation in serum K + as well as significant reduction in renal tissue MDA, GST, MPO and KIM-1 when compared to the TAA group, but still significantly higher compared to controls except for

Background: Testicular torsion is one of the emergencies affecting mostly adolescent males, resulting in sub-fertility if not rapidly and efficiently managed. Oxidative stress, inflammatory response as well as immunological reactions were implicated in its pathogenesis. Recently interest in studying the non-skeletal effects of vitamin D is growing, many researches indicates its antioxidant, antiinflammatory and immuno-modulatory effects. Aim of the Work: Investigating the possible conservative effect of vitamin D 3 treatment on testicular endocrinal function in testicular torsion/detorsion rat model, and elucidating its possible underlying mechanism. Materials and Methods: 24 young adult male albino rats, weighing 120-160 g., were randomly allocated into 3 groups, 8 in each group, Sham operated (SHAM), Testicular torsion/detorsion (T/D) and Testicular torsion/detorsion; vitamin D 3 treated (T/D; D 3) groups. All rats were subjected to measurement of absolute and relative testicular weight (ATW and RTW, respectively), assessment of testicular endocrinal function by serum total testosterone and inhibin B levels. In addition to determination of serum antisperm antibody (AsAb). Testicular tissue was examined for oxidative stress markers; malondialdeyde (T. MDA) and glutathione peroxidase (T, GPx), as well as inflammatory marker; myeloperoxidase (T. MPO). Results: Testicular T/D resulted in significant reduction in ATW, RTW, serum testosterone and inhibin B levels with significant elevation in serum AsAb, T. MDA and T. MPO when compared with SHAM group. On treatment with vitamin D 3 , RTW was significantly increased as compared with T/D group but still significantly less than SHAM group. Serum testosterone level was significantly increased when compared with both SHAM and T/D groups. Inhibin B was significantly increased as compared with T/D group but still not normalized as being significantly less than SHAM group. Serum AsAb, T. MDA and T. MPO were significantly decreased when compared with T/D group, being normalized for T. MDA but still significantly higher for serum AsAb and T. MPO when compared with SHAM group, however, T. GPx was significantly increased as compared with both SHAM and T/D groups. Conclusion: Vitamin D 3 could retrieve the testicular endocrinal dysfunction induced by Torsion/Detorsion by its antioxidant, antiinflammatory and immuno-modulatory effects.

Background Aging is associated with cardiovascular and metabolic changes, increasing the susceptibility to acute myocardial infarction (AMI). Intermittent fasting (IF) has a beneficial effect on the age-associated cardiovascular diseases. The present study was planned to investigate the possible protective effect of IF against acute AMI induced by isoproterenol (ISO) in old rats and its possible underlying mechanisms mediated by heart and pancreatic autophagy. Thirty Male Wistar rats were divided into four groups: adult; old; Old-ISO (rats subjected to AMI by ISO) and Old-F-ISO groups (rats were subjected to IF for 4 weeks and AMI by ISO). Results IF significantly increased the mRNA expression of cardiac Atg-5 and pancreatic Atg-7 in Old-F-ISO versus old and adult groups. This was associated with a significant decrease in serum troponin-I, serum creatine kinase (CK-MB), cardiac malondialdehyde and cardiac TNF-α, fasting plasma glucose, and HOMA-IR in Old-F-ISO compared to Old-ISO group. Also, IF significantly decreased the age-related overall and visceral obesity in Old-F-ISO versus old and Old-ISO groups. Histological studies revealed attenuation of the local inflammatory response in Old-F-ISO versus Old-ISO group. Pancreatic Atg-7 and heart Atg-5 were significantly increased in Old-ISO versus old rats. Conclusions IF protects against acute AMI in old rats, possibly, via chronic activation of heart Atg-5 and pancreatic Atg-7, and alleviation of age-related overall and visceral obesity. Thus, IF could be a dietary lifestyle modification for attenuation of the susceptibility to acute AMI in aged population. On the other hand, acute activation of heart and pancreatic autophagy by ISO might augment cardiac injury.

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