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.

Artemisinin has received much attention in the treatment of malaria in recent years, and it is now considered as a potential candidate to reduce coccidial infection in chickens. It is a sesquiterpene compound which has been isolated from Aretemisia annua for the first time. The present study aimed to investigate the occurrence of artemisinin in A. sieberi (AS) and to test the anticoccidial effects of plant extract in broiler chickens. The aerial parts of the plant were collected during different seasons from Yazd Province, in the centre of Iran. The artemisinin content of the AS was extracted with petrol ether and analysed by high-performance liquid chromatography using UV detection. Anticoccidial effects of the plant extract were tested on chicks challenged with various species of Eimeria. The infected chickens were treated with doses of 1 or 2.5 mg/kg per day artemisinin via oral administration of plant extract. The analytical results showed that the level of artemisinin in AS was 0.2% and 0.14% of dried weight (DW) of plant materials in summer and autumn, respectively. Treatment of experimentally infected chickens with AS extracts showed that artemisinin was able to reduce the severity of coccidial infection induced by Eimeria tenella and E. acervulina, but not E. maxima. The anticoccidial effects of artemisinin were shown by significant decrease in output of number of oocysts per gram of faeces in chickens challenged with different species of Eimeria. This study showed that the levels of artemisinin in AS were comparable with those in other species including A. annua, and that the extract of this plant can reduce coccidial infection in broiler chickens.

AIM:To assess the hepatic changes after induction of different periods of renal ischemia. METHODS:Rats were subjected to either sham operation or ischemia (30, 45 and 60 min) followed by 60 min reperfusion. Liver and renal functional indices were measured. Hepatic glutathione (GSH) and ferric reducing antioxidant power levels and the concentration of interleukin (IL)-10 and tumor necrosis factor (TNF-α) were evaluated. Portions of liver and kidney tissues were fixed for histological evaluation. RESULTS:Forty-five minutes renal ischemia followed by 60 min reperfusion caused significant changes in liver structure and a significant reduction in renal function. These rats showed a significant decrease in liver GSH, as well as a significant increase in TNF-α and IL-10 concentrations. These results demonstrated that renal ischemia caused changes in liver histology, function, oxidative stress and inflammatory status, which led to a reduction in hepatic antioxidant capacity. With 30 min ischemia, the magnitude of these changes was less than those with 45 or 60 min ischemia. CONCLUSION:A minimum of 45 min ischemia is needed to study the effects of renal injury on the liver as a remote organ.

The proteinase-activated receptors (PARs) are a novel family of G protein-coupled receptors, and their effects in neurodegenerative diseases remain uncertain. Alzheimer’s disease (AD) is a neurodegenerative disorder defined by misfolded protein accumulation with concurrent neuroinflammation and neuronal death. We report suppression of proteinase-activated receptor-2 (PAR2) expression in neurons of brains from AD patients, whereas PAR2 expression was increased in proximate glial cells, together with up-regulation of proinflammatory cytokines and chemokines and reduced IL-4 expression (p < 0.05). Glial PAR2 activation increased expression of formyl peptide receptor-2 (p < 0.01), a cognate receptor for a fibrillar 42-aa form of β-amyloid (Aβ1–42), enhanced microglia-mediated proinflammatory responses, and suppressed astrocytic IL-4 expression, resulting in neuronal death (p < 0.05). Conversely, neuronal PAR2 activation protected human neurons against the toxic effects of Aβ1–42 (p < 0.05), a key component of AD neuropathogenesis. Amyloid precursor protein-transgenic mice, displayed glial fibrillary acidic protein and IL-4 induction (p < 0.05) in the absence of proinflammatory gene up-regulation and neuronal injury, whereas PAR2 was up-regulated at this early stage of disease progression. PAR2-deficient mice, after hippocampal Aβ1–42 implantation, exhibited enhanced IL-4 induction and less neuroinflammation (p < 0.05), together with improved neurobehavioral outcomes (p < 0.05). Thus, PAR2 exerted protective properties in neurons, but its activation in glia was pathogenic with secretion of neurotoxic factors and suppression of astrocytic anti-inflammatory mechanisms contributing to Aβ1–42-mediated neurodegeneration.

Liver ischemia/reperfusion (IR) injury is a complex phenomenon that may cause local as well as remote organ injuries. Reactive oxygen species (ROS) along with many pro- and anti- inflammatory cytokines are implicated in the development of organ injury. The renal functional, histological, oxidative stress and inflammatory indices were studied during a short and a longer period of liver IR. Rats were subjected to either sham operation or 90 min partial liver ischemia followed by 4 or 24 h of reperfusion. Serum ALT, AST, ALK and LDH levels, BUN and creatinine, renal MDA level, SOD and catalase activities were evaluated as well as serum IL-6 and IL-10 concentrations along with renal histological evaluation. Ninety minutes liver ischemia /4 h reperfusion caused an increase in BUN and renal MDA levels and a decrease in SOD and catalase activities. It also caused an increase in serum IL-6 and IL-10 levels. 24 h liver reperfusion resulted in a reduction in BUN levels and lower oxidative damages demonstrated by a decrease in renal MDA levels and an increase in renal SOD and catalase activities comparing to 4 h reperfusion group. Evaluations indicated improvement in histology such as less cytoplasmic vacuolation and lower tubular debris. Serum inflammatory indices (IL-6 and IL-10 levels) were also reduced. This study showed that liver IR damage causes renal injury including functional, inflammatory and oxidative status changes. The remote kidney damage was then improved by continuing reperfusion from 4 to 24 h.