Bronchi ; cytology ; metabolism ; Cell Line ; Epithelial Cells ; cytology ; metabolism ; Erythromycin ; pharmacology ; Glutamate-Cysteine Ligase ; genetics ; metabolism ; Glutathione ; genetics ; metabolism ; Humans ; RNA, Messenger ; genetics ; metabolism ; Up-Regulation ; drug effects

OBJECTIVETo investigate the protective effects of docosahexaenoic acid (DHA) and nervonic acid (NA) on the learning and memory abilities in rats exposed to 1-bromopropane (1-BP) and their action mechanisms.

METHODSForty male Wistar rats (specific pathogen-free) were randomly divided into 4 groups (n = 10 for each), i.e., solvent control group, 1-BP (800 mg/kg) group, NA (150 mg/kg) + 1-BP (800 mg/kg) group, and DHA (500 mg/kg) + 1-BP (800 mg/kg) group. The rats were given respective test substances by gavage for 7 d. The Morris water maze (MWM) test was performed from days 8 to 12 to evaluate the rats' learning and memory abilities. After MWM test, rats were sacrificed in the next day, and cerebral cortex was quickly dissected and homogenized in an ice bath. The supernatant of the obtained homogenate was collected to measure the content of glutathione (GSH) and malondialdehyde (MDA) and the activities of glutathione reductase (GR) and γ-glutamate cysteine ligase (γ-GCL).

RESULTSThe MWM spatial navigation test showed that the 1-BP group had significantly longer escape latency and significantly longer total swimming distance compared with the control group (P<0.05), while the DHA+1-BP group had significant decreases in escape latency and total swimming distance compared with the 1-BP group (P<0.05). The spatial probe test showed that the number of platform crossings was significantly greater in the DHA+1-BP group and NA+1-BP group than in the 1-BP group (P<0.05); compared with the control group, the 1-BP group had a significantly lower ratio of time spent in the zone around the platform to total time (P < 0.05), and the ratio was significantly higher in the DHA+1-BP group than in the 1-BP group (P < 0.05). Compared with the control group, the 1-BP group had a 18.1% decrease in GSH content, and DHA could significantly reverse 1-BP-induced decrease in GSH content (P < 0.05). Compared with the 1-BP group, the DHA+1-BP group and NA+1-BP group had significantly decreased MDA content (P < 0.05), the DHA+1-BP group had significantly increased GR activity (P < 0.05), and the NA+1-BP group had significantly increased γ-GCL activity (P < 0.05).

CONCLUSIONThe rats exposed to 1-BP have oxidative stress in the brain and impaired cognitive function. DHA and NA can reduce 1-BP-induced cognitive function impairment in rats, possibly by increasing the activities of GR and γ-GCL and the content of GSH in the brain.

Animals ; Behavior, Animal ; Brain ; drug effects ; Docosahexaenoic Acids ; pharmacology ; Fatty Acids, Monounsaturated ; pharmacology ; Glutamate-Cysteine Ligase ; metabolism ; Glutathione ; metabolism ; Glutathione Reductase ; metabolism ; Hydrocarbons, Brominated ; toxicity ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory ; drug effects ; Oxidative Stress ; Rats ; Rats, Wistar

The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.
Acetaminophen/toxicity* ; Animals ; Antioxidants/pharmacology* ; Glutamate-Cysteine Ligase/pharmacology* ; Glutathione ; Interleukin-6/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Liver ; Medicine, Tibetan Traditional ; Mice ; NF-E2-Related Factor 2/metabolism* ; NF-kappa B/metabolism* ; RNA, Messenger/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

The present study was designed to observe the protection of Grateloupia filicina polysaccharide (GFP) against hepatotoxicity induced by Dioscorea bulbifera L in mice and its underlying mechanism. GFP was intragastrically (ig) given to mice at various doses. After 6 days, the mice were treated with ethyl acetate extract of Dioscorea bulbifera L (EF, ig). Serum levels of alanine/aspartate aminotransferase (ALT/AST), alkaline phosphatase (ALP), total bilirubin (TB) were measured, and liver histological evaluation was conducted. Furthermore, reductions of liver glutathione (GSH) amount and glutamate cysteine ligase (GCL) activity were tested. The expressions of GCL-c, GCL-m, and HO-1 (heme oxygenase-1) in liver were observed by Western-blot. The results showed that GFP (600 mg x kg(-1)) decreased EF-induced the increase of serum ALT, AST and TB, and GFP (400, 600 mg x kg(-1)) inhibited EF-induced the increase of serum ALP. Liver histological evaluation showed that the liver injury induced by EF was relieved after treated with GFP. GFP further increased liver GSH amount and reversed EF-induced the decrease of GCL activity. The Western-blot result showed that GFP augmented EF-induced the increase of HO-1, and reversed EF-induced the decrease of GCL-c. In conclusion, GFP can act against the oxidative stress liver injury induced by Dioscorea bulbifera L in mice.
Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Chemical and Drug Induced Liver Injury ; blood ; metabolism ; Dioscorea ; toxicity ; Glutamate-Cysteine Ligase ; metabolism ; Glutathione ; metabolism ; Heme Oxygenase-1 ; metabolism ; Heterocyclic Compounds, 4 or More Rings ; antagonists & inhibitors ; isolation & purification ; toxicity ; Liver ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred ICR ; Oxidative Stress ; drug effects ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology ; Random Allocation ; Rhodophyta ; chemistry

This study is to investigate the protection effect of schisandrin B (Sch B) against oxidation stress of HK-2 cells induced by cisplatin and the mechanisms involved. HK-2 cells were cultured and divided into different groups: solvent control group, cisplatin exposure group, positive group, Sch B treatment group. Cell viability and toxicity were evaluated by MTT and LDH assay. GSH level and SOD enzymes activities were also measured. DCFH-DA as fluorescence probe was used to detect ROS level by fluorescence microplate reader. Nrf2 translocation was detected by Western blotting. Real time Q-PCR was used to detect expressions of NQO1, HO-1 and GCLC mRNA level. The results showed that Sch B could significantly inhibit the decline of cell viability induced by cisplatin treatment (P < 0.05) and the protective effect was in a dose dependent manner. Furthermore, Sch B treatment significantly inhibited the increase of ROS level induced by cisplatin and reversed the decrease of GSH level (P < 0.05). When Sch B concentration was up to 5 micromol x L(-1), SOD enzyme activities were also enhanced significantly compared with that of the cisplatin group (P < 0.05). It was shown that Sch B could cause nuclear accumulation of Nrf2 in association with downstream activation of Nrf2 mediated oxidative response genes such as GCLC, NQO1 and HO-1. These results suggested Sch B could protect against the oxidative damage of HK-2 cells induced by cisplatin via the activation of Nrf2/ARE signal pathway.
Antineoplastic Agents ; toxicity ; Antioxidants ; isolation & purification ; pharmacology ; Cell Line ; Cell Survival ; drug effects ; Cisplatin ; toxicity ; Cyclooctanes ; isolation & purification ; pharmacology ; Glutamate-Cysteine Ligase ; genetics ; metabolism ; Glutathione ; metabolism ; Heme Oxygenase-1 ; genetics ; metabolism ; Humans ; Kidney Tubules, Proximal ; cytology ; metabolism ; L-Lactate Dehydrogenase ; metabolism ; Lignans ; isolation & purification ; pharmacology ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; metabolism ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Polycyclic Compounds ; isolation & purification ; pharmacology ; RNA, Messenger ; metabolism ; Reactive Oxygen Species ; metabolism ; Schisandra ; chemistry ; Signal Transduction ; Superoxide Dismutase ; metabolism

This study was to investigate the effect of peoniflorin on the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream signal molecules in the hippocampus of Alzheimer's disease (AD) rats for exploring the mechanism of peoniflorin protecting hippocampal neurons. AD model rats were established by bilateral intrahippocampal injection of beta-amyloid(1-42) (Abeta(1-42)) and divided randomly into 3 groups: AD model group, peoniflorin low-dose (15 mg x kg(-1)) group and peoniflorin high-dose (30 mg x kg(-1)) group. The vehicle control rats were given bilateral intrahippocampal injection of solvent with the same volume. After peoniflorin or saline was administered (ip) once daily for 14 days, the hippocampuses of all animals were taken out for measuring the expressions of Nrf2, heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthethase (gamma-GCS) mRNA by reverse transcription PCR, determining the contents of glutathione (GSH), malondialdehyde (MDA) and carbonyl protein (CP) using colorimetric method, and for assaying the expressions of neuronal apoptosis inhibitory protein (NAIP) and Caspase-3 by immunohistochemical staining method. The results showed that peoniflorin markedly increased the expressions of Nrf2, HO-1 and gamma-GCS mRNA, enhanced the level of GSH and decreased the contents of MDA and CP in the hippocampus, as compared with the model group. Peoniflorin also improved the NAIP expression and reduced the Caspase-3 expression in the hippocampus neurons. In conclusion, peoniflorin protects against the Abeta(1-42)-mediated oxidative stress and hippocampal neuron injury in AD rats by activating the Nrf2/ARE pathway.
Alzheimer Disease ; chemically induced ; metabolism ; physiopathology ; Amyloid beta-Peptides ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Caspase 3 ; metabolism ; Glucosides ; pharmacology ; Glutamate-Cysteine Ligase ; genetics ; metabolism ; Glutathione ; metabolism ; Heme Oxygenase (Decyclizing) ; genetics ; metabolism ; Hippocampus ; metabolism ; Male ; Malondialdehyde ; metabolism ; Monoterpenes ; pharmacology ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Neuronal Apoptosis-Inhibitory Protein ; metabolism ; Neurons ; metabolism ; Oxidative Stress ; drug effects ; Peptide Fragments ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The aim of this study is to investigate the protection effect of tanshinone IIA (Tan) against triptolide (TP)-induced liver injury and the mechanisms involved. Acute liver injury was induced by intraperitoneal injection of TP (1 mg x kg(-1)) in mice. The activities of AST, ALT and LDH in serum and the levels of GSH, GST, GSH-PX, SOD, CAT and MDA in liver tissue were detected. The histopathological changes of liver tissues were observed after HE staining. Nrf2 translocation in liver tissue was detected by Western blotting, and real-time PCR was used to measure the expression levels of GCLC, NQO1 and HO-1 mRNA. The results showed that pretreatment with Tan significantly prevented the TP induced liver injury as indicated by reducing the activities of AST, ALT and LDH (P < 0.01). Tan pretreatment also prevented TP-induced oxidative stress in the mice liver by inhibiting MDA and restoring the levels of GSH, GST, SOD and CAT (P < 0.05). Parallel to these changes, pretreatment with Tan could attenuate histopathologic changes induced by TP. Furthermore, the results indicated that Tan pretreatment caused nuclear accumulation of Nrf2 as well as induction of mRNA expression of antioxidant response element (ARE)-driven genes such as GCLC, NQO1 and HO-1. These results indicated that Tan could protect against TP-induced acute liver injury via the activation of Nrf2/ARE pathway.
Animals ; Antioxidant Response Elements ; drug effects ; Chemical and Drug Induced Liver Injury ; metabolism ; pathology ; Diterpenes ; toxicity ; Diterpenes, Abietane ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Epoxy Compounds ; toxicity ; Glutamate-Cysteine Ligase ; genetics ; metabolism ; Heme Oxygenase-1 ; genetics ; metabolism ; Liver ; metabolism ; pathology ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; metabolism ; NF-E2-Related Factor 2 ; metabolism ; Phenanthrenes ; toxicity ; RNA, Messenger ; metabolism ; Signal Transduction ; drug effects