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Polydeoxyribonucleotide (PDRN) is an agonist of the A2A adenosine receptors. We evaluated the effects of PDRN on liver regeneration induced by partial hepatectomy (PH) in rats, focusing on cell proliferation. Proliferating cell nuclear antigen (PCNA) as an indicator of cell proliferation was targeted to determine whether PDRN treatment could promote proliferation of hepatic cells in regenerating liver. Male Sprague-Dawley rats were divided into three groups: normal group (n= 3) without PH (sham operated), control groups (n= 12) with saline injection after PH, and experimental groups (n= 12) with i.p. injection of 8 mg/kg of PDRN immediately after PH. Light microscopically, liver regeneration induced by PH involved proliferation of various hepatic cells including parenchymal cells and Kupffer cells. The disintegration (1 or 2 days after PH) and remodeling (4 days after PH) of hepatic plate and increase of sinusoids (6 days after PH) were sequentially observed. These regenerative processes occurred relatively earlier in the experimental groups. By western blotting, the expression of PCNA increased in the early stage, reached its peak at 1 and 2 days after PH, and decreased thereafter. By immunohistochemistry, the intensities of PCNA staining in the experimental groups were more obvious at various days after PH. By electron microscopy using immunogold labeling for PCNA, the gold particles were largely observed in heterochromatin and nucleolus in hepatic cells. The results of immunochemistry and western blotting for PCNA showed the similar pattern in most groups. These findings suggest that PDRN treatment to hepatectomized rat could accelerate liver regeneration through rapid cell proliferation. [ABSTRACT FROM PUBLISHER]

We prepared recombinant human interleukin-2 (rhIL-2) and studied its pretreated influence on liver regeneration and the blood profile in partially (67%) hepatectomized (PH) male Sprague-Dawley rats. Rats were injected in the tail vein with rhIL-2 three times per day for 3 consecutive days and 67% underwent a partial hepatectomy (PH). Five days after the PH, liver tissue and blood samples were analyzed for liver regeneration and hematological changes. The weight of the liver in the rhIL-2 pretreated groups increased in a dose-dependent manner; with the highest treatment (24 × 10 IU/kg), the maximum liver weight of 88.6% was exhibited. The control group showed a gradual increase to 76.3% of the original liver weight. A histological analysis of the liver showed an increase in proliferating cell nuclear antigen (PCNA)-positive cells in rhIL-2 pretreated rat livers. The rate of hepatocyte proliferation also increased significantly in primary cultured rat liver cells following rhIL-2 treatment. These results suggest that pretreatment with rhIL-2 may play adjuvant roles in liver regeneration after PH. [ABSTRACT FROM AUTHOR]

Liver regeneration is a process involving highly organized and ordered tissue growth triggered by the loss of liver tissue. This process has remained a fascinating topic in medicine. In this study, we examined the effects of recombinant human interleukin-2 (rhIL-2) in rats under cirrhotic conditions. Thirty rats were divided into three groups, and liver cirrhosis was induced by injecting diethylnitrosamine for 2 weeks and CCl4for 8 weeks. After induction of cirrhosis, rhIL-2 was injected daily into their tail vein for three days and then hepatocyte growth factor (HGF), immunocytes in the blood, and TNF-αproduction were analyzed. The analysis showed that TNF-αwas significantly downregulated in the liver without significant changes in nitric oxide and caspase-3/7 activities in primary cultured liver cells. In terms of the number of immunocytes, there were no significant differences between the control and the treated groups. However, HGF levels were significantly higher in the treated groups than the control (saline administration) group. Treatment of rhIL-2 significantly increased the proliferation of primary cultured liver cells. The proliferation rates of primary cultured liver cells were correlated with the upregulation of HGF by treatment with rhIL-2in vivoandin vitro.These results suggest that rhIL-2 affects liver regeneration, which is at least related to the upregulation of HGF under cirrhotic conditions in rats. [ABSTRACT FROM AUTHOR]

Objectives Modified Bo-Yang-Hwan-O-Tang (mBHT) is an improved herbal formula of BHT, which has been widely used to treat ischaemic stroke in East Asia, by the addition of five herbs having anti-ischaemic properties. In this study, we investigated whether mBHT would reduce cerebral ischaemic injury in rats. Methods Sprague-Dawley rats were subjected to a 90-min middle cerebral artery occlusion (MCAO) and subsequent 22-h reperfusion. mBHT was administered either intraperitoneally twice 15 min before and 15 min after, or orally once 30 min or 120 min after the onset of MCAO (50 or 200 mg/kg each). Key findings Intraperitoneal administration of mBHT markedly reduced the cerebral infarct size and neurological deficit caused by MCAO/reperfusion. mBHT treatment also significantly improved long-term survival rate after cerebral ischaemic injury. Oral administration of mBHT 30 min after ischaemia also markedly reduced the infarct size after cerebral ischaemia. The anti-ischaemic effect of mBHT was significantly, but not fully, reduced when mBHT-induced hypothermia was abolished. In cultured cortical neurons, we further found that mBHT decreased oxygen-glucose deprivation/re-oxygenation-evoked neuronal injury by inhibiting production of reactive oxygen species, decrease in mitochondrial transmembrane potential, and activation of caspase-3. However, mBHT did not inhibit N-Methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. Conclusions Taken together, our data suggest that mBHT has multiple anti-ischaemic properties and would be a good therapeutic herbal prescription for the treatment of cerebral ischaemic stroke. [ABSTRACT FROM AUTHOR]