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OBJECTIVE@#Acetaminophen (APAP) overdose is a common cause of liver injury. This study aimed to investigate the protective effect of honokiol (Hon) against APAP-induced hepatotoxicity and its potential mechanism.@*METHODS@#C57BL/6 mice were administrated with Hon (10 and 30 mg/kg) after APAP (300 mg/kg) treatment. On 1.5 h and 5 h after Hon treatment, mice were sacrificed. Serum and liver were collected. And then, liver injury-related indexes, APAP metabolism-related indexes, mitochondrial respiratory chain function-related indexes, and mitochondrial membrane function-related protein expression were evaluated.@*RESULTS@#It was found that Hon significantly decreased serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activity and glutathione (GSH) depletion, increased hepatic catalase (CAT) and GSH peroxidase (GSH-Px) activities, reduced hepatic MDA and 3-nitrotyrosine contents, inhibited hepatic CYP1A2 activity and APAP protein adducts (APAP-CYS) formation. Meanwhile, oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV in mitochondrial respiratory chain was increased, whereas the release of H2O2 in the mitochondria was decreased following Hon treatment. Furthermore, Hon markedly down-regulated p-JNK in both cytosol and mitochondria, and obviously inhibited the release of apoptosis inducing factor (AIF) and endonuclease G (EndoG) from mitochondria to cytosol.@*CONCLUSION@#Hon alleviated APAP-induced liver injury through the following pathways: Reducing the production of APAP-CYS by inhibiting CYP1A2 activity; Ameliorating hepatic oxidative stress by increasing the levels of hepatic CAT, GSH-Px and GSH; Improving mitochondrial respiratory chain function by promoting oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV; Improving the function of mitochondrial membrane by inhibiting p-JNK and its translocation to mitochondria, thereby reducing the release of AIF and EndoG.
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The postoperative nervous system and neurocognition-related complications have become an important issue of research focus with the gradual increase of the survival rate after liver transplantation. Compared to other solid organ transplantation, the incidence of nervous system complications after liver transplantation is higher and closely related to death. This paper mainly overviewed the nervous system complications, neurocognition-related complications after liver transplantation and the risk factors inducing these complications. It also discussed how to evaluate, monitor, and prevent these complications in order to provide reference for future studies.
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The degradation kinetics of chlorogenic acid (5-CQA), cryptochlorogenic acid (4-CQA), and neochlorogenic acid (3-CQA) in aqueous solution at 37 degrees C and different pH values (7.05, 7.96, 9.25) were investigated in the present work. The results indicated that 3-, 4- and 5-CQA tended to remain stable in acidic pH circumstance, and unstable in neutral and alkaline pH circumstance. With the increase of the alkalinity, the degradation of 3-, 4- and 5-CQA was increased leading to a less amount of total CQA and was satisfactorily described by the Weibull equation. Meanwhile, caffeic acid was not detected after the degradation of CQA. Moreover, the degradation of 3-CQA and 5-CQA tended to be converted to 4-CQA, and the degradation of 4-CQA tended to be converted to 3-CQA rather than 5-CQA. The comparison of the degradation kinetics parameters of 3-, 4- and 5-CQA at neutral and alkaline pH values showed that the orders of the rate constant (k) values were 4-CQA > 3-CQA > 5-CQA, while the orders of the degradation half life (t½) values were 4-CQA < 3-CQA < 5-CQA, indicating the orders of the stabilities of 3-, 4- and 5-CQA at 37 degrees C and neutral and alkaline pH values were 4-CQA < 3-CQA < 5-CQA.
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BACKGROUND:Although the mechanism why neuronal cels wil die after transient cerebral ischemia has not been completely elucidated, many researches nowadays have investigated the pathological mechanism in the level of celular organs, such as mitochondria. OBJECTIVE:To summarize and discuss the functions of neuronal mitochondria and apoptosis signaling pathways in transient cerebral ischemia. METHODS: A computer-based online retrieval was performed to search papers in CNKI and PubMed databases using the key words of “cerebral ischemia, mitochondrion, apoptosis, reactive oxygen species, reperfusion, superoxide dismutase, nitric oxide synthase, Bcl-2 protein family, review” in Chinese and English, respectively. Papers published recently or in the prestigious journals were selected in the same field. After excluding objective-independent papers and repeated studies, 50 papers were included for further analysis. RESULTS AND CONCLUSION:Recently mitochondria are found to play an important role after transient cerebral ischemia by producing a lot of reactive oxygen species to activate many kinds of signaling pathways and regulate mitochondria-mediated apoptosis. Reactive oxygen cannot only induce biomacromolecule injury but also induce apoptosis signal transduction. Deeply investigation is needed on the pathological mechanism after transient cerebral ischemia.
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Objective Research has indicated that hydrogen sulfide(H2S) can regulate the function of N-methyl-D-aspartate re-ceptors(NMDARs) in the brain, but its effect on brain resuscitation requires further investigation.The study was to speculate the effect of H2 S on brain resuscitation as well as the underlying mechanism of neuroresuscitation by investigating the effects of hydrogen sulfide and hypo-thermia on the expression of NR2A, NR2B and phospho-cAMP response element binding protein (p-CREB) of NMDARs in the hippocampus after global cerebral ischemia following by reperfusion. Methods 100 male SD rats were randomly divided into five groups(n=20):sham operation group, model group, mild hypothermia group, NaHS group, NaHS combined mild hypothermia group.Pulsinelli-Brierley four-ves-sel occlusion method was induced to build the injury rat model by reperfusion after global cerebral ischemia .After 15 minutes'ischemia, im-mediate injection of 14μmol/kg NaHS was performed intraperitoneally on NaHS group and NaHS combined mild hypothermia group , while skin cooling(rectal temperature=32-33℃) was done on mild hypothermia group and NaHS combined mild hypothermia group .6 hours late,r hip-pocampus were extracted from rat heads.Respectively, spectrophotometer was applied to measure the content of H2S, Western blot for the expres-sions of NR2 A,NR2 B and pC-REB, and RTP-CR for mRNA level of brain derived neurotrophic (BDNF). HE staining was also performed on brain tissues 72hours after reperfusion on 4 rats from each group to evaluate the pathological changes of pyramidal neurons in CA1 region. R esul ts The content of H 2 S increased in each of the four groups after ischemia-reperfusion compared with sham operation group ( 15.2 ±2.0 nmol/g) (P0.05).The gray values of NR2A and NR2B in each group increased compared with sham operation group(P1 in NaHS group and NaHS combined mild hy-pothermia group.Compared with the expression of p-CREB(0.55 ±0.06) in model group, there were significant increases in mild hypother-mia group(0.99 ±0.15), NaHS group(1.05 ±0.12), NaHS combined mild hypothermia group(1.02 ±0.15)(P<0.05).Compared with the expression of BNDF mRNA(0.83 ±0.12) in model group, there were significant increases in mild hypothermia group (1.11 ±0.13), NaHS group(1.27 ±0.16), NaHS combined mild hypothermia group(1.35 ±0.16)(P<0.05).In comparison to model group, there were signifi-cant alleviation in the injury of pyramidal neurons in hippocampal CA1 region in mild hypothermia group, NaHS group, NaHS combined mild hypothermia group, with the best effect in NaHS combined mild hypothermia group . Conclusion Hydrogen sulfide combined mild hypo-thermia can selectively activate synaptic NMDA receptors and trigger the prosurvival CREB signaling pathway to exert brain resuscitation .
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Objective To evaluate the effect of hydrogen sulfide combined with mild hypothermia on cerebral ischemia-reperfusion (I/R) injury in rats. Methods Eighty male SD rats, aged 3 months, weighing 250-300 g, were randomly divided into 5 groups ( n = 16 each): sham operation group (group S), cerebral I/R group,mild hypothermia group (group M), sodium hydrosulfide group (group NaHS) and NaHS + mild hypothermia group (group NM). In group I/R, M, NaHS and NM, cerebral I/R was induced by occlusion of 4 vessels (cauterization of bilateral vertebral arteries and 15 min occlusion of bilateral common carotid arteries) followed by reperfusion. In group NaHS and NM, intraperitoneal NaHS 14 μmol/kg was injected immediately after reperfusion, while the equal volume of normal saline was injected in the other three groups. At the same time, the rectal temperature was reduced to 32-33 ℃ within 15 min, lasting for 6 h, in group M and NM, while it was maintained at 36-37 ℃by physical method in other groups. Twelve rats of each group were sacrificed after 6 h of reperfusion, and then the hippocampus was removed for determination of the content of H2 S by using spectrophotometer and the expression of p-CREB and BDNF mRNA by using Western blot and RT-PCR respectively. Four rats in each group were sacririced after 72 h of reperfusion and then the hippocampus was removed for microscopic examination. Results The cerebral I/R injury was attenuated in group M, NaHS and NM compared with group I/R, with the slightest injury in group NM. The H2S content was significantly higher in group I/R, M, NaHS and NM than in group S, and in group NaHS and NM than in group I/R and M. The expression of p-CREB and BNDF mRNA was significantly higher in group I/R, M, NaHS and NM than in group S, and in group M, NaHS and NM than in group I/R. The BDNF mRNA expression was significantly higher in group NM than in group M and NaHS. There was no significant difference in the H2S content and the expression of p-CREB and BNDF mRNA between group NaHS and M.Conclusion Hydrogen sulfide combined with mild hypothermia can attenuate cerebral I/R injury by up-regulating the expression of p-CREB and BDNF mRNA in hippocampus in rats.
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Objective To investigate the effect of hydrogen-rich saline combined with mild hypothermia on cerebral ischemia-reperfusion (IR) injury in rats. Methods Fifty male SD rats, aged 9-10 weeks, weiging 250-300 g, were randomly divided into 5 groups (n= 10 each): sham operation group (group S), group IR, hygrogen-rich saline group (group H), mild hypothermia group (group M) and hydrogen-rich saline + mild hypothermia group (group HM). In group IR, H, M and HM cerebral IR was induced by 15 min ligation of bilateral carotid artery followed by 6 h reperfusion. In group H and HM intraperitoneal hydrogen-rich saline 5 ml/kg was injected immediately after reperfusion, while the equal volume of normal saline was injected instead of hydrogen-rich saline in the other three groups. At the same time, the rectal temperature was maintained at 37-38 ℃ in group S,IR and M, while it was reduced to 32-34 ℃ by physical method within 15 min, lasting for 6 h, in group M and HM. The animals were sacrificed after 6 h of reperfusion, and then the hippocampus was removed for microscopic examination. The expression of HO-1 and content of MDA and TNF-α were determined by Western blot. Results The cerebral IR injury was attenuated in group H, M and HM compared with group IR, with the slightest injury in group HM. The expression of HO-1 and content of MDA and TNF-α were significantly higher in group IR, H, M and HM than in group S. The expression of HO-1 was significantly higher, while the content of MDA and TNF-α were lower in group H, M and HM than in group IR, and in group HM than in group H and M. There was no significant difference in the expression of HO-1 and content of MDA and TNF-α between group H and M. Conclusion Hydrogen-rich saline combined with mild hypothermia can attenuate cerebral I/R injury in rats via up-regulating the expression of HO-1 and decreasing the content of MDA and TNF-α in hippocampus.
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Objective To investigate the changes in high voltage-activated (HVA) calcium current in dorsal root ganglion (DRG) neurons isolated from rats with neuropathic pain. Methods Pathogen-free male SD rats aged 4-6 weeks weighing 180-220 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg. Neuropathic pain was induced by ligation of L5 spinal nerve between DRG and sciatic nerve. The nerve was transected distal to the ligature. The animals which showed positive signs of neuropathic pain were decapitated on the 14th postoperative day. L5 and L4 DRGs were isolated and the neurons in the ganglia were enzymatically dissociated (group L5 and L4). The control group received no surgery (group C). The HVA Ca2+ current was recorded using whole-cell patch clamp technique. Results Peak calcium current density was significantly lower in group L5 and L4 than in group C, and was significantly lower in group L5 than in group L4 . Halfactivation value (Va 1/2) was also significantly lower in group L5 than in group C and L4 (P ＜ 0.05). The relative contribution of N-type to the total HVA Ca2+ current was significantly greater in group L5 than in group C and L4(P ＜ 0.05). There was no significant difference in the steady-state inactivation curves among the 3 groups. Conclusion In rats with neuropathic pain, the HVA Ca2+ current in the injured DRG neurons may play a key role in the induction of neuropathic pain.
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Objective To investigate the role of A2B adenosine receptor(A2BAR)in 6% HES 130/0.4-induced reduction of pulmonary capillary permeability in a rat model of sepsis.Methods Fifty male SD rats weighing 250-300 g were randomly divided into 5 groups(n = 10 each): group Ⅰ sham operation(group S);group Ⅱ sepsis(group CLP);group Ⅲ ,Ⅳ,Ⅴ low,medium,high dose HES(group H1,2,3).The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg.Left carotid artery and left femoral vein were cannulated for MAP and HR monitoring and fluid and drug administration.Sepsis was induced by cecal ligation and puncture (CLP).6% HES 130/0.4 7.5,15.0 and 30.0 ml/kg were infused iv over 2 h in group H1,2,3 respectively at 4 h after CLP.The animals were sacrificed at 6 h after CLP.The lungs were isolated for determination of pulmonary capillary permeability(by iv Evans blue injection),the expression of A2BAR and the contents of cAMP,protein kinase A(PKA),TNF-α,IL-6 and IL-10 in the lung tissue.Results CLP significantly increased pulmonary capillary permeability,A2BAR expression and cAMP,IL-6 and TNF-α contents in the lung tissue in group Ⅱ as compared with group S.0.6% HES 130/0.4 significantly reduced pulmonary capillary permeability,increased A2BAR expression,cAMP,PKA and IL-10 and decreased IL-6 and TNF-αcontents in the lung tissue in group H1,2,3 as compared with group CLP.6% HES 130/0.4 decreased pulmonary capillary permeability and up-regulated A2BAR expression in a dose-dependent manner.6% HES 130/0.4 15.0 ml/kg was most effective in increasing cAMP and PKA contents in the lung and depressing inflammatory response.Conclusion 6% HES 130/0.4 decreases pulmonary capillary permeability in a rat model of sepsis by up-regulating A2BAR expression in lung tissue.