This broad, narrative review highlights the roles of sialic acids as acidic sugars found on cellular membranes. The role of sialic acids in cellular communication and development has been well established. Recently, attention has turned to the fundamental role of sialic acids in many diseases, including viral infections, cardiovascular diseases, neurological disorders, diabetic nephropathy, and malignancies. Sialic acid may be a target for developing new drugs to treat various cancers and inflammatory processes. We recommend the routine measurement of serum sialic acid as a sensitive inflammatory marker in various diseases.

Gentamicin (GM) is an antibiotic belonging to an aminoglycoside family that might induce nephrotoxicity in human and animal models via oxidative stress. Toll-like receptors (TLRs) are part of innate immune systems that participate in inflammatory responses. In this regard, we investigated the effect of GM on kidney functional and structural parameters, enzymatic antioxidant levels, and mRNA expression of TLR4 and IL6 in the rat kidney. Adult male Sprague Dawley rats were randomly divided into two groups (n = 10): Control and Gentamicin (100 mg/kg, i.p.). After ten days of GM administration, a blood sample was taken, and the kidneys were removed. The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) were measured. Furthermore, the right kidney was preserved in formalin 10% for hematoxylin and eosin (H&E) staining, and the left kidney was kept at −80 °C for molecular and oxidative indexes analysis. Administration of GM caused tubular damages and functional disturbance. So that, Cr and BUN values in the GM group were higher than Control group. Furthermore, molecular findings showed upregulation of TLR4 and IL-6 mRNA expression in renal tissue of the GM-received group. In this study, superoxide dismutase (SOD) activity was slightly increased as a compensatory mechanism in response to elevated malondialdehyde (MDA) levels in the GM-treated group. On the other hand, the activity of catalase (CAT) and glutathione peroxidase (GPx) were significantly declined. Our results demonstrated that oxidative stress and subsequent TLR4 upregulation signaling pathways are involved in GM-induced nephrotoxicity.

Introduction: Remote ischemic conditioning upregulates endogenous protective pathways in response to ischemia-reperfusion injury. This study tested the hypothesis that limb remote ischemic per-conditioning (RIPerC) exerts cardioprotective effects via the renin-angiotensin system (RAS)/inducible nitric oxide synthase (iNOS)/apelin pathway. Methods: Renal ischemia-reperfusion injury (I/R) was induced by bilateral occlusion of the renal pellicles for 60 minutes, followed by 24 hours of reperfusion; sham-operated rats served as controls. RIPerC was induced by four cycles (5 minutes) of limb ischemia-reperfusion along with bilateral renal ischemia. The functional disturbance was evaluated by renal (BUN and creatinine) and cardiac (troponin I and lactate dehydrogenase) injury biomarkers. Results: Renal I/R injury increased renal and cardiac injury biomarkers that were reduced in the RIPerC group. Histopathological findings of the kidney and heart were also suggestive of amelioration injury-induced changes in the RIPerC group. Assessment of cardiac electrophysiology revealed that RIPerC ameliorated the decline in P wave duration without significantly affecting other cardiac electrophysiological changes. Further, renal I/R injury increased the plasma (322.40±34.01 IU/L), renal (8.27±1.10 mIU/mg of Protein), and cardiac (68.28±10.28 mIU/mg of Protein) angiotensin-converting enzyme (ACE) activities in association with elevations in the plasma and urine nitrite (25.47±2.01 & 16.62±3.05 μmol/L) and nitrate (15.47±1.33 & 5.01±0.96 μmol/L) levels; these changes were reversed by RIPerC. Further, renal ischemia-reperfusion injury significantly (P=0.047) decreased the renal (but not cardiac) apelin mRNA expression, while renal and cardiac ACE2 (P<0.05) and iNOS (P=0.043) mRNA expressions were significantly increased compared to the sham group; these effects were largely reversed by RIPerC. Conclusion: Our results indicated that RIPerC protects the heart against renal ischemia-reperfusion injury, likely via interaction of the apelin with the RAS/iNOS pathway.

Renal ischemic/reperfusion (I/R) injury leads to acute kidney injury with multiple organ damage. Klotho has anti-inflammatory and antioxidant capacities and protects the heart and kidneys against I/R injury. This study aimed to determine whether Klotho is involved in the cardioprotective effect of limb ischemic per-conditioning (LIPerC) during renal I/R injury. Sprague-Dawley rats were randomly divided into three groups: Sham, I/R underwent bilateral occlusions of the renal pedicles for 60 min followed by reperfusion for 24 h, and LIPerc + I/R, which underwent cyclic I/R of the left femoral artery performed during renal ischemia. After 24 h, plasma, urine, and kidney and heart tissue were collected. Renal and cardiac functional biomarkers, soluble Klotho, oxidative stress, and inflammatory mediators were assessed. Renal I/R injury caused a decrease in soluble Klotho and increased blood urea nitrogen, creatinine, troponin I, and LDH (p < 0.01). Moreover, it established oxidative stress and histopathological changes in the kidney and myocardium. The levels of TNF-α and NF-κB were upregulated, and Klotho (p < 0.01) was downregulated in the post-I/R cardiac tissue. LIPerC improved the histopathological changes and suppressed the oxidative status and inflammation. LIPerC could not compensate for the Klotho expression in the heart tissue. However, correlations between plasma levels and heart expression of Klotho with oxidative and inflammatory signals could confirm the role of Klotho in the healing effect of LIPerC on remote cardiac injury. LIPerC may potentially ameliorate the remote cardiac dysfunction induced by renal I/R injury by modulating oxidative and inflammatory signals associated with the Klotho protein.