Ellagic acid ameliorates cuprizone-induced acute CNS inflammation via restriction of microgliosis and down-regulation of CCL2 and CCL3 pro-inflammatory chemokines.

Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuro-inflammatory conditions. Microglia making the innate immune system of the central nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory processes. In this study, neuro-protective effects of EA on cuprizone (Cup)-induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow containing 0.2 % Cup for 3 weeks to induce acute neuro-inflammation predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p) from the first day of the Cup diet. Microglia activation (microgliosis) and expression of microglia related chemokines during Cup challenge were examined. Results shows that EA significantly decreased the number of activated microglia cells (Iba-1+ cells) and also restricted proliferation of these cell population (Iba-1+/Ki67+ cells) in dose dependent manner. Consequently, concentration of microglial pro-inflammatory chemokines including monocyte chemoattractant protein-1/Chemokine (C-C motif) ligand 2 (MCP-1/CCL2), and macrophage inflammatory protein 1-alpha/Chemokine (C-C motif) ligand 3 (MIP-1-α/CCL3) dramatically reduced in CC after EA treatment. According to this results, we conclude that EA is a suitable therapeutic agent for moderation brain damages in neuro-inflammatory diseases.

Postconditioning is protective in renal reperfusion injury only in male rats. A gender difference study.

PURPOSE: We investigated the impact of sex on the protective effect of postconditioning (POC), a series of brief ischemia-reperfusion (IR) cycles at the reperfusion onset, as a recently described novel approach to attenuate renal IR injury. In this study, the left renal pedicles of uni-nephrectomized male and female rats were clamped for 45 minutes followed by 24 hours of reperfusion as IR groups. Uni-nephrectomized, sham-operated male and female rats served as control groups. Ischemic postconditioning was performed using 4 cycles of 10 seconds of IR of renal pedicle at the end of the ischemia. Twenty-four hours later, BUN (blood urea nitrogen), plasma creatinine (Cr), and renal histological changes, as well as kidney levels of MDA (malondialdehyde) and SOD (superoxide dismutase) as oxidative stress markers were evaluated to detect the protective effect of POC against IR injury in rats. RESULTS: Induction of IR resulted in significant reduction in renal function, demonstrated by increase in plasma Cr and BUN, histological changes and oxidative stress in both genders. Application of POC afforded significant protection against these injuries in male rats, namely decreased levels of BUN and Cr, histological improvements and less oxidative damages. However, there were no significant differences in the above-mentioned parameters in female rats. CONCLUSION: While POC is shown to be beneficial against renal IR injury in male rats, it did not show any protective effect in female rats.

NeuroProtective effects of adenosine receptor agonist coadministration with ascorbic acid on CA1 hippocampus in a mouse model of ischemia reperfusion injury.

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.

Hepatic changes during various periods of reperfusion after induction of renal ischemia in rats.

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)-alpha. 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-alpha and IL-10 concentrations. The most significant changes among inflammatory factors in the liver were observed at 3 hours of reperfusion: TNF-alpha, 616 +/- 41 vs 215 +/- 16, and IL-10, 926 +/- 73 vs 125 +/- 34, pg/100 mg tissue (P

Changes in serum and renal vitamin E levels in deoxycorticosterone acetate-salt hypertensive rats.

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.