Liver ischemia-reperfusion (IR) injury is inevitable in surgical procedures such as hepatic resection and liver transplantation. It represents a leading cause of liver graft dysfunction and primary nonfunction after transplantation. Phosphodiesterase (PDE) inhibitors are emerging as effective drugs able to reduce IR damage. The aim of this study was to investigate the effect of selective PDE-3 inhibitor olprinone (Olp) against liver IR injury. Male Wistar rats were subjected to 1 h of partial warm ischemia (70%) followed by 6 h of reperfusion. Before ischemia, rats were treated with saline (IR group), Olp (Olp group), or Olp with Akt inhibitor LY294002 (Olp plus LY group). After reperfusion, hepatic injury (transaminase activities), mitochondrial damage (glutamate dehydrogenase activity), oxidative stress (malondialdehyde and glutathione concentrations and catalase and superoxide dismutase activities), and protein kinase Akt activation were evaluated. Rat treatment with Olp reduced liver injury, prevented mitochondrial damage, decreased lipid peroxidation, and enhanced antioxidant enzymes. Also, Olp induced a significant activation in protein kinase Akt. Inhibition of Akt with LY294002 abolished all of the protective effects of Olp. In conclusion, Olp treatment may be an effective strategy in reducing liver IR injury through oxidative stress prevention and Akt activation.
Background As a clinical and non-invasive tool, the AGE Reader measures skin autofluorescence (SAF) to estimate the accumulation of advanced glycation end products (AGEs) in the skin. Accumulation of AGEs has been implicated in several inflammation-associated diseases, including diabetes and cardio-metabolic diseases. This study aimed to assess SAF in subjects with and without cardiovascular risk (CVR) factors and examine the association between SAF and various bio-clinical parameters. Methods In a cross-sectional study, we included 250 participants between 19 and 86 years of age divided into two groups: a healthy group (n = 88) and subjects with CVR factors (n = 162 in total, diabetes n = 48, hypertension n = 62, and both n = 52). We assessed skin AGE measures and biological and clinical data.Results SAF was significantly higher in subjects with CVR factors than in healthy participants (2.42 ± 0.38 vs 1.90 ± 0.29 respectively; p < 0.001). SAF was associated with age, gender, BMI, duration of diabetes, HbA1c, triglyceride, and obesity. Multivariate analysis showed that age and duration of diabetes were the independent determinants of SAF. The ROC analysis indicated that a SAF > 2.25 AU was the optimal cut-off point to predict the presence of diabetes and/or hypertension and dyslipidemia (p < 0.001). Conclusion This Tunisian population-based study shows an increased SAF level in subjects with diabetes and/or hypertension and dyslipidemia compared to healthy subjects. The AGE Reader device is a rapid and non-invasive tool in clinical practice to evaluate and screen CVR factors in Tunisia with a North African phototype.
Background: Cardiovascular disease (CVD) is the main reason for morbidity and mortality of patients in hemodialyis. Skin autofluorescence (SAF), a noninvasive measurement method, reflects tissue accumulation of advanced glycation end products (AGEs) that has been implicated in CVD as a strong marker. The aim of this study was to evaluate SAF profile in hemodialysis patients and to assess the association between SAF and heart failure. Methods: In a cross-sectional study, we included 60 hemodialysis (HD) patients who were subdivided in two groups: a HD group without heart failure (n=39) and a HD group with heart failure (n=21). Skin AGEs accumulation was measured by AGE Reader device and clinical data was obtained. Results: HD patients showed a SAF value at 2.90 (2.40-3.60). HD patients with diabetes mellitus have an increased SAF levels compared to HD patients without diabetes [3.20 (2.90-3.95) vs. 2.70 (2.30-3.30) AU, P = 0.021; respectively]. Furthermore, HD patients with heart failure showed a significant increased SAF levels compared to HD patients without heart failure [3.65 (2.90-4.12) vs. 2.60 (2.30-3.20) AU, P <0.001; respectively]. SAF was associated with age, gender, and duration of dialysis. The ROC analysis indicated that SAF at 3.05 AU was optimal cut-off point for presence of heart failure (P <0.001). Conclusion: SAF might be a rapid and helpful tool in clinical practice as a potential marker for evaluating and screening heart failure in HD patients non-invasively and might be used as predictor for clinicians. Keywords: skin autofluorescence; advanced glycation end products; hemodialysis; heart failure.
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