The present study aimed to investigate the renoprotective effect of therapeutic hypothermia (TH) on renal ischemia-reperfusion injury (RI/RI) induced by asphyxial cardiac arrest (CA) in rats. A total of 48 male rats were randomly divided into five groups: i) Sham (n=6); ii) Normothermia + CA (Normo.) (n=14); iii) Normo. and 2 h of TH after return of spontaneous circulation (ROSC) (n=12); iv) Normo. and 4 h of TH after ROSC (n=9); and v) Normo. and 6 h of TH after ROSC (n=7). All rats except the Sham group underwent asphyxia CA and were sacrificed 1 day after ROSC. The survival rate increased from 42.8% in the Normo. group to 50, 66.6 and 85.7% in the groups with 2, 4 and 6 h of TH after CA, respectively. TH attenuated the histopathological changes of the renal tissues following ROSC and the levels of blood urea nitrogen, serum creatinine and malondialdehyde in renal tissues. On immunohistochemistry, the relative optical density of nuclear erythroid-related factor-2 (Nrf2) and heme oxygenase (HO-1) expression in renal tissues increased in the Normo. group compared with that in the Sham group and exhibited further significant increases at 6 h of TH after ROSC. In conclusion, TH attenuated renal injury and increased the expression of Nrf2 and HO-1 in a TH treatment time-dependent manner.
Although multi-organ dysfunction is associated with the survival rate following cardiac arrest (CA), the majority of studies to date have focused on hearts and brains, and few studies have considered renal failure. The objective of the present study, therefore, was to examine the effects of therapeutic hypothermia on the survival rate, pathophysiology and antioxidant enzymes in rat kidneys following asphyxial CA. Rats were sacrificed one day following CA. The survival rate, which was estimated using Kaplan-Meier analysis, was 42.9% one day following CA. However, hypothermia, which was induced following CA, significantly increased the survival rate (71.4%). In normothermia rats with CA, the serum blood urea nitrogen level was significantly increased one day post-CA. In addition, the serum creatinine level was significantly increased one day post-CA. However, in CA rats exposed to hypothermia, the levels of urea nitrogen and creatinine significantly decreased following CA. Histochemical staining revealed a significant temporal increase in renal injury after the normothermia group was subjected to CA. However, renal injury was significantly decreased in the hypothermia group. Immunohistochemical analysis of the kidney revealed a significant decrease in antioxidant enzymes (copper-zinc superoxide dismutase, manganese superoxide dismutase, glutathione peroxidase and catalase) with time in the normothermia group. However, in the hypothermia group, these enzymes were significantly elevated following CA. Collectively, the results revealed that renal dysfunction following asphyxial CA was strongly associated with the early survival rate and therapeutic hypothermia reduced renal injury via effective antioxidant mechanisms.
To investigate the role of Nrf2/HO-1 in renal histopathological ailments time-dependently in asphyxial cardiac arrest (CA) rat model. Methods: Eighty-eight Sprague Dawley male rats were divided into five groups of eight rats each. Asphyxial CA was induced in all the experimental rats except for the sham group. The rats were sacrificed at 6 hours, 12 hours, one day and two days post-CA. Serum blood urea nitrogen (BUN), creatinine (Crtn) and malondialdehyde from the renal tissues were evaluated. Hematoxylin and eosin and periodic acid-Schiff staining were done to evaluate the renal histopathological changes in the renal cortex. Furthermore, Nrf2/HO-1 immunohistochemistry (ihc) and western blot analysis were performed after CA. Results: The survival rate of rats decreased in a time-dependent manner: 66.6% at 6 hours, 50% at 12 hours, 38.1% in one day, and 25.8% in two days. BUN and serum Crtn markedly increased in CA-operated groups. Histopathological ailments of the renal cortical tissues increased significantly from 6 hours until two days post-CA. Furthermore, Nrf2/HO-1 expression level significantly increased at 6 hours, 12 hours, and one day. Conclusion: The survival rate decreased time-dependently, and Nrf/HO-1 expression increased from 6 hours with the peak times at 12 hours, and one day post-CA.
Background Globally, ischemic stroke is a major health threat to humans that causes lifelong disability and death. Mentha arvensis (MA) has been used in traditional medicine to alleviate oxidative stress and inflammation-related disorders. In the present study, the neuroprotective properties of fermented MA (FMA) extract were investigated in the gerbil and SH-SY5Y cells. model of transient global cerebral ischemia. Methods Bilateral common carotid artery occlusion-induced transient global cerebral ischemia in gerbil and hydrogen peroxide (H2O2)-mediated neurotoxic effects in human neuroblastoma cells (SH-SY5Y) were investigated. FMA (400 mg/kg) was orally administered for 7 days before induction of ischemic stroke. To evaluate the neuroprotective activity of FMA, we implemented various assays such as cell viability assay (MTT), lactate dehydrogenase (LDH) assay, histopathology, immunohistochemistry (IHC), histofluorescence, and western blot. Results FMA pretreatment effectively decreased transient ischemia (TI) induced neuronal cell death as well as activation of microglia and astrocytes in the hippocampal region. The protective effects of FMA extract against H2O2-induced cytotoxicity of SH-SY5Y cells were observed by MTT and LDH assay. However, FMA pretreatment significantly increased the expression of the antioxidant marker proteins such as superoxide dismutase-1 (SOD-1) and superoxide dismutase-2 (SOD-2) in the hippocampus and SH-SY5Y cells. Furthermore, the activation of mitogen-activated protein kinase (MAPK) further activated a cascade of outcomes such as neuroinflammation and apoptosis. FMA pretreatment notably decreased TI and H2O2 induced activation of MAPK (c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38) proteins in hippocampus and SH-SY5Y cells respectively. Besides, pretreatment with FMA markedly reduced H2O2 mediated Bax/Bcl2 expression in SH-SY5Y cells. Conclusion Thus, these results demonstrated that neuroprotective activities of FMA might contribute to regulating the MAPK signaling pathway.
Olanzapine (OLNZ) is used to treat psychotic disorders. To look into the neurological basis of this phenomenon, we investigated the neuroprotective effects of OLNZ in gerbils and SH-SY5Y cells. Gerbils were subjected to transient global cerebral ischemia (TGCI) by blocking both common carotid arteries, and OLNZ (10 mg/kg) was injected intraperitoneally. Hydrogen peroxide (H2O2) was used to induce oxidative-stress-mediated damage in the SH-SY5Y cells. The results indicated that OLNZ administration markedly reduced neuron damage and glial cell triggering within CA1 zone of the hippocampus. We used RNA sequencing to assess the numbers of up-and downregulated genes involved in TGCI. We found that OLNZ treatment downregulated the expression of complement-component-related genes and the expression of mitogen-activated protein kinases (MAPKs) in the hippocampus. In cells, OLNZ co-treatment significantly improved cell viability and reduced lactate dehydrogenase (LDH), and reactive oxygen species (ROS) generation. Expression of antioxidant superoxide dismutase-1,2 enzymes (SOD-1, SOD-2) was also intensely upregulated by OLNZ, while the expression of MAPKs and NF-κB were reduced. Co-incubation with OLNZ also regulated apoptosis-related proteins Bax/Bcl-2 expression. Finally, the results demonstrated that treatment with OLNZ showed neuroprotective effects and that the MAPK pathway could involve in the protective effects.
Aralia elata (AE) is an anti-inflammatory, polyphenolic containing medicinal plant. However, little is known about AE and its application to ulcerative colitis (UC). This study aimed to confirm AE extract's antioxidant and anti-inflammatory effects in vivo and in vitro. The in vitro antioxidant activity was evaluated by measuring total polyphenol and flavonoid content in AE extract. AE extract (10 000 mg/L) contained 186.8 mg GAE/g polyphenol and 81.9 mg QE/g flavonoid. Mice were divided into 6 groups, including control, which received normal saline, and treatment groups, which received dextran sodium sulfate (DSS) with or without AE extract (250, 500, and 1000 mg/kg). RAW 264.7 macrophage cells were divided into 2 groups: control and treatment. RAW 264.7 macrophage cells treated with sterile double distilled water, 1 mg/L lipopolysaccharide (LPS), and AE extracts (25, 50, 75, 100 µg/mL) were used to assess the cytotoxicity and anti-inflammatory activity. High-performance liquid chromatography, enzyme-linked immunosorbent assay (ELISA) kits, and histology were employed to analyze the AE extract contents, nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, as oxidative stress markers. In addition, the disease activity index (DAI) and cytotoxicity were determined in mice and cells, respectively. High-performance liquid chromatography analysis revealed that AE extract is rich in chlorogenic acid (96 ± 0.01 mg/g). DSS increased the DAI and levels of TNF-α, IL-1β, and immune cell infiltration compared with those of the control animals. Furthermore, LPS eventually reduced cell viability and increased the levels of NO, TNF-α, IL-1β, and IL-6 in contrast to control cells. After treatment, a noticeable reduction was observed in the levels of DAI, NO, TNF-α, IL-1β, and IL-6 compared to those without AE treatments. Overall, AE extract is safe and had anti-inflammatory properties. Therefore, AE extract can be considered a potential pre-treatment supplement for UC.
Introduction: Cardiac arrest (CA) often leads to severe brain damage, resulting in neurological disorders and high mortality rates. Hypothermia treatment (HT) is commonly used in clinical practice after CA/cardio-pulmonary resuscitation (CA/CPR) because it has been shown to improve neurological outcomes and increase survival rates. Olanzapine, a medication known to induce hypothermia, has not been extensively studied in the context of CA/CPR. This study aimed to investigate the neuroprotective effects and mechanisms of olanzapine-induced hypothermia (OIH) following ROSC. Male Sprague-Dawley rats were subjected to the following conditions: (i) Sham: no asphyxial CA + saline, (ii) CA: asphyxial CA + saline, and (iii) OCA: asphyxial CA + olanzapine treatment after the return of spontaneous circulation (ROSC). Result CA/CPR resulted in high mortality, severe neurological impairments, and hippocampal neuron damage observed after 5 days in the asphyxia CA group. These pathological complications were ameliorated by olanzapine treatment. OIH also protected the pyramidal neurons in the CA1 region of the hippocampus. The expression of antioxidant factors SOD-1, SOD-2, and CAT were upregulated in the olanzapine-treated group compared to the CA group. Moreover, olanzapine treatment following asphyxial CA reduced the expression of the pro-inflammatory factor COX-2 and the nuclear transcription factor NF-κB, which was sustained for up to 5 days compared to the CA group. OIH provides protection against cerebral injury following ROSC by enhancing the expression of antioxidant and anti-inflammatory factors. Conclusion The results of our study demonstrate that Olanzapine, an atypical antipsychotic medication, induces a noteworthy reduction in body temperature in the asphyxial CA rat model. The effectiveness of hypothermia treatment was evident by its antioxidant and anti-inflammatory mechanisms. Therefore, we suggest olanzapine as a promising therapeutic agent for alleviating cerebral injury via hypothermia in patients with CA.
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