Acute ischemia-reperfusion (IR) of the limbs initiates both local and systemic injuries by triggering a systemic inflammatory response. Cyclooxygenase-2 (COX-2), an endogenous inducible enzyme, rises in response to inflammation. The aim of this work is to investigate the role of celecoxib, a selective COX-2 inhibitor, in abrogating remote organ dysfunction after hindlimb IR in rats by comparing it with a standard hemorrheologic drug (pentoxifylline). Rats were divided into 4 groups (n = 6 each), group I (sham control, received saline and was kept under anaesthetic for 7 h). Group II (IR, subjected to 1 h of hindlimb tourniquet ischemia and 6 h reperfusion). Group III and IV (pretreated with 200 mg/kg pentoxifylline or 10 mg/kg celecoxib, respectively, intragastrically for 7 days before IR induction). Administration of pentoxifylline or celecoxib produced significant reduction in SGPT, serum creatinine, malondialdehyde, and tumor necrosis factor-alpha and significant increase in blood pH, blood adenosine triphosphate, and reduced glutathione compared with the IR group (p < 0.05). There was no significant difference among the pretreated groups. Histopathologic findings of the IR lung showed alveolar destruction, inflammatory cells infiltration, mast cell degranulation, and necrosis of the gastrocnemius muscle fibres. These changes were attenuated in the pretreated groups. In conclusion, celecoxib can ameliorate IR induced remote organ injury to a similar extent as pentoxifylline through its antiinflammatory and antioxidant action.

BackgroundOval cells, specific liver progenitors, are activated in response to injury. The human umbilical cord blood (hUCB) is a possible source of transplantable hepatic progenitors and can be used in cases of severe liver injury. We detected the effect of hUCB stem cell transplantation on natural response of oval cells to injury.MethodsTwenty-four female albino rats were randomly divided into three groups: (A) control, (B) liver injury with hepatocyte block, and (C) hUCB transplanted group. Hepatocyte block was performed by administration of 2-acetylaminofluorene (2-AAF) for 12 days. CCL4 was administrated at day 5 from experiment start. Animals were sacrificed at 9 days post CCL4 administration, and samples were collected for biochemical and histopathological analysis. Oval cell response to injury was evaluated by the percentage of oval cells in the liver tissue and frequency of cells incorporated into new ducts.ResultsImmunohistochemical analysis of oval cell response to injury was performed. There was significant deviation in the hUCB-transplanted (4.9 ± 1.4) and liver injury groups (2.4 ± 0.9) as compared to control (0.89 ± 0.4) 9 days post injury. Detection of oval cell response was dependant on OV-6 immunoreactivity. For mere localization of cells with human origin, CD34 antihuman immunoreactivity was performed. There was no significant difference in endogenous OV-6 immunoreactivity following stem cell transplantation as compared to the liver injury group.ConclusionsIn vivo transplantation of cord blood stem cells (hUCB) does not interfere with natural oval cell response to liver injury.

Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome, and has been etiologically associated with insulin resistance (IR). The histopathology of NAFLD ranges between simple steatosis and nonalcoholic steatohepatitis (NASH), with or without fibrosis. The aim of the present study was to examine the effect of heparin on steatohepatitis and hepatic-induced nitric oxide synthase (iNOS) expression in mice. Male mice were divided into four groups, which included the normal basal diet (control), high fat (HF) diet, HF diet + heparin (treatment group) and heparin control groups. After eight weeks from the initiation of the experiment, blood was collected and livers were harvested for biochemical analysis and histological studies. Serum levels of aspartate aminotransferase, alanine aminotransferase, hepatic triglyceride (TG) and hydroxyproline, as well as the IR, superoxide anion generation and mRNA expression of the hepatic iNOS enzyme were evaluated. Liver specimens were processed for histopathological and immunohistopathological evaluation. Heparin administration decreased the levels of the liver enzymes, IR, superoxide generation, hepatic TG, hydroxyproline and iNOS expression when compared with the HF diet group. These changes were associated with an improvement in inflammation and fibrosis observed via histopathological examination. Therefore, heparin treatment attenuates hepatic injury in steatohepatitis.

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