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Background: The effect of ischemia/reperfusion (I/R) injury on kidney has been under investigation for many years. But the changes in liver function and oxidative stress status in renal I/R injury is not well known. Recent studies suggest a crosstalk between liver and kidneys. The aim of the present study was to assess liver changes after induction of various degrees of renal I/R injury. Methods: This is an experimental study conducted on 20 male rats that were obtained from animal house of Physiology Department. Twenty male rats were subjected to either sham operation or ischemia (30, 45 and 60 min) followed by 60 min reperfusion periods. Blood samples were drawn post-operatively and plasma creatinine, BUN, ALT and AST were measured. Hepatic glutathione (GSH) and FRAP (ferric reducing antioxidant power) levels and the concentration of IL-10 and tumor necrosis factor (TNF) -alpha were evaluated. Results: Both 45 and 60 min ischemia followed by 1h reperfusion periods resulted in significant increases in plasma creatinine (11.1±1.7mg/dl and 1.24±0.07mg/dl vs 0.55±0.15mg/dl, p<0.05) and BUN (34±3.85mg/dl and 35.0±2.81mg/dl vs 23.75±1.1mg/dl, p<0.05). These rats showed a significant decrease in liver GSH as well as significant increase in TNF-α & IL-10 concentrations. Conclusion: Renal ischemia causes changes in liver function and oxidative stress status. A minimum of 45 min ischemia is needed to study the effects of renal injury on liver as a remote affected organ. [ABSTRACT FROM AUTHOR]

Recent studies have documented that remote organs are affected by ischemic injury to the kidney. Here we studied whether the liver also suffers damage during induction of renal ischemia-reperfusion in rats and compared this to bilateral nephrectomy. Hepatic levels of tumor necrosis factor-alpha increased significantly after 6 and 24 h of renal ischemia or nephrectomy. Malondialdehyde, an index of lipid peroxidation, increased while total glutathione was decreased in the liver in both the renal ischemia and nephrectomy groups, suggesting activation of oxidative stress. Expression of liver spermine-spermidine acetyl transferase, an enzyme upregulated in early phases of hepatic injury was significantly increased 6 h after either kidney ischemia or nephrectomy. Apoptosis was increased in hepatocytes 24 h after nephrectomy. We also found histological evidence of hepatocyte injury following both ischemia and bilateral nephrectomy. Infusion of reduced glutathione, before the induction of renal ischemia, significantly improved liver architecture and was associated with a reduction in hepatic malondialdehyde and serum alanine transaminase levels. Our study shows that acute kidney ischemia or renal failure activates oxidative stress and promotes inflammation, apoptosis, and tissue damage in hepatocytes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recent studies have suggested that ischemic damage to the kidneys causes liver tissue alterations. Thus, the morbidity and mortality in patients with acute renal failure (ARF) may be related to liver complications as well as to renal injury. The aim of the present study was to assess the hepatic changes during various periods of reperfusion after induction of renal ischemia. Methods: Forty male rats were subjected to either a sham operation or to a 45-minute ischemia followed by 1, 3, 6, or 24 hours of reperfusion. Arterial pressure was continuously monitored. Blood samples were drawn to measure serum creatinine and blood urea nitrogen (BUN). Results: We evaluated hepatic concentrations of interleukin (IL)-10 and tumor necrosis factor (TNF)-α. Ischemia reperfusion (IR) caused significant reductions in renal function as demonstrated by increased values of serum creatinine and BUN. These rats also showed significant increases in hepatic TNF-α and IL-10 concentrations. The most significant changes among inflammatory factors in the liver were observed at 3 hours of reperfusion: TNF-α, 616 ± 41 vs 215 ± 16, and IL-10, 926 ± 73 vs 125 ± 34, pg/100 mg tissue (P ≤ .05). Twenty-four–hour reperfusion reduced the extent of liver injury. Discussion: Renal IR affects liver inflammatory status, possibly due to increased renal production or impaired clearance of mediators of tissue injury, namely proinflammatory cytokines. The reduction in liver injury at 24 hours of reperfusion compared with the other groups, suggested activation of late-protective mechanisms. These observations may be important for clinical interventions to reduce the morbidity and mortality of ARF. [Copyright &y& Elsevier]

GM2 gangliosidosis is a hereditary lysosomal storage disorder resulting from mutations in the Hexosaminidase A (HEXA) gene, which leads to a deficiency in the activity of the β HEXA isoenzyme. This condition is characterized by the accumulation of GM2 ganglioside within the lysosomes, which subsequently induces neurological consequences. This study sought to find causal variations in a consanguineous family with two affected children strongly suspected of GM2 gangliosidosis and a 17-week fetus. We conducted whole-exome sequencing (WES) on the genomic DNA of the proband to identify the causative variants. Subsequently, we performed confirmation and co-segregation analysis of the identified variant with the phenotype in the proband, fetus, and family members using Sanger sequencing. Also, cytogenetic evaluation was performed using amniocentesis to identify fetal chromosomal abnormalities. After conducting bioinformatic analysis and applying data filtering techniques, we found a novel homozygous variation [NM_000520.6:c.1378T>C:p.W460R] within the HEXA gene. The identified variant was further confirmed through Sanger sequencing in the proband and segregated with GM2 gangliosidosis and infantile Tay-Sachs disease (TSD) in the family. The single alteration was pathogenic and considered a missense variant that altered the protein features by substituting the highly conserved amino acid tryptophan with arginine at position 460 in the HEXA protein sequence. The findings of this study offer additional support for the genetic heterogeneity of GM2 gangliosidosis and broaden the mutational gene spectrum of this inherited metabolic disorder by finding a novel HEXA pathogenic variant that had not previously been reported in these patients. [ABSTRACT FROM AUTHOR]

Ischemic brain injury is a leading cause of sever neurological and neurobehavioral deficits and death. The hippocampus plays vital roles in learning and memory processes and it is impaired by ischemic insults. Cerebral ischemia/reperfusion leads to Oxidative stress damage impairing the hippocampus. Here we tested whether ascorbic acid and adenosine receptor played a neuroprotective role in a mouse brain ischemia model induced by common carotid arteries occlusion. Adult male mice were randomly assigned into nine experimental groups. The animals were subjected to ischemia by the ligation of common carotid arteries for 15 min. Drugs were injected intrapritoneally once daily for 7 days. Behavioral tests performed at day 14 and then mice were killed at day 21 and their brains were fixed for microscopic studies and some samples were prepared for western blot analysis. Western blot analysis utilized to evaluate the expression of apoptosis-related proteinsin the hippocampus. Short-term memory was assessed by shuttle-box test. Our findings revealed that administration of vitamin C and N6-cyclopentyladenosine (CPA) significantly attenuated ischemia-induced brain injury. Vitamin C and CPA administration increased the expression of anti-apoptotic protein Bcl-2 and decreased the expression of pro-apoptotic protein Bax in the ischemic mice. Ischemia caused short-term memory loss that was improved by vitamin c and CPA treatment. Our results demonstrate that treatment with vitamin C and adenosine receptor agonist attenuated cerebral ischemia/reperfusion-induced brain injury as a potential neuroprotective agent. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hypertension is an important risk factor for the progression of chronic renal disease, which may result in the development of end-stage renal disease. Since reactive oxygen species are implicated in the induction of hypertension, antioxidants have been used to reduce blood pressure and renal impairment in animal models and in human hypertension. However, the available data are not conclusive. Methods: To investigate oxidative stress in hypertension, we evaluated renal and serum vitamin E levels as the most effective antioxidant to reduce lipid peroxidation by high-performance liquid chromatography among rats subjected to deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks. Renal levels of malondialdehyde (MDA) as a marker of cell lipid peroxidation were also assayed in treated rats. Systolic blood pressure (SBP) was measured in conscious rats by the tail-cuff method using a PowerLab/4sp data acquisition system. Results: SBP increased significantly in DOCA-salt-treated rats compared to the sham group after 4 weeks of treatment. Serum vitamin E levels were significantly lower and renal MDA concentrations significantly higher in treated compared to sham rats. However, renal vitamin E levels were also significantly higher among treated compared to sham rats. Discussion: Decreased plasma vitamin E levels and increased renal MDA levels show systemic and local oxidative stress in DOCA-salt-treated rats. However, the higher renal vitamin E level suggested a local compensatory mechanism. Vitamin E administration might be appropriate, as significant decreases in vitamin E levels were observed in the serum of DOCA-salt-treated rats. [Copyright &y& Elsevier]