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The effects of diallyl sulfide (DAS) and the potential mechanisms were investigated on lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced acute liver injury in mice. DAS (50, 100, 200 μmol/kg) were orally given 1 h prior to LPS (10 μg/kg)/D-GalN (500 mg/kg) intraperitoneal injection. Serum and liver were collected at 8 h after LPS/D-GalN treatment. DAS Pretreatment reduced the activities of serum aminotransferase and attenuated histopathological damage in LPS/D-GalN-induced liver injury. Additionally, LPS/D-GalN-induced liver oxidative stress was ameliorated by DAS pretreatment, as evidenced by the decreased content of MDA and increased level of GSH, SOD, CAT in liver. Moreover, LPS/D-GalN-induced the excessive levels of TNF-α, IL-1β and MCP-1 in serum and liver was decreased by DAS pretreatment. Furthermore, DAS pretreatment attenuated LPS/D-GalN-induced hepatocyte apoptosis, as evidenced by TUNEL staining and protein expression of cleaved caspase3, Bax and Bcl-2 in liver. DAS also up-regulated the expression of p-PI3K p85 and p-Akt in a dose-dependent manner, and Akt inhibitor MK-2206 weakened the inhibitory effect of DAS on hepatocyte apoptosis induced by LPS/D-GalN. In conclusion, the results suggest that DAS exerts the protective effect on LPS/GalN-induced acute liver injury, and this effects possibly by suppressing oxidative stress, inflammation and regulating hepatocyte apoptosis via the PI3K/Akt pathway., (Copyright © 2018. Published by Elsevier Ltd.)

Occupational exposure to carbon disulfide (CS 2 ) exhibits central nervous systems toxicity. But the mechanism is unclear. The present study was designed to investigate the relationship between the CNS damage and cognitive dysfunction caused by CS 2 , and eventually reveal the possible oxidative-related mechanism of hippocampus pathological changes in CS 2 exposed rats. Male Wistar rats were administrated with CS 2 at dosage of 200, 400 and 600 mg/kg for consecutive 20 days, respectively. Cognitive performances were evaluated by Morris water maze tests. Thionin and immunohistochemical analysis were used to investigate the hippocampal neuron damage, and the expression of apoptosis related proteins (cleaved-caspase 3, Bax and Bcl-2) were detected to explore the possible mechanisms of neuronal loss. Oxidative stress parameters were checked by commercial assay kits. Rats exposed to CS 2 displayed cognitive dysfunction manifested as decreased spatial learning ability and memory lesion. Pathological changes and significant neuron loss were observed in hippocampus, especially in CA1 and CA3 sub-regions. Mitochondria-dependent apoptosis pathway was implicated in the CS 2 -induced neuronal loss which was demonstrated by the up-regulation of cleaved-caspase 3 and Bax accompanied with down-regulation of Bcl-2. Furthermore, extensive oxidative stress induced by CS 2 was also revealed by the measurement of ROS, RNS, MDA, GSH&GSSG and antioxidant enzymes (CAT, T-SOD, and GSH-Px). Our study suggested that oxidative stress mediated hippocampal neuron apoptosis might play an important role in CS 2 induced CNS damage and cognitive dysfunction.

Background: Multiple sclerosis (MS) is a chronic autoimmune demyelination disorder of the central nervous system (CNS) and its etiology remains unknown. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines, which contribute to the development and progression of multiple sclerosis. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress is involved in the inflammation leading demyelination and neurodegeneration in the pathogenesis of multiple sclerosis., Summary: The present study aims to determine two biochemical markers of oxidative stress: TAC and MDA and to show their correlations whether oxidative stress reaction occurs in the demyelination through analyzing samples including peripheral blood and cerebrospinal fluid (CSF) from patients with relapsing-remitting MS (RR-MS). Totally, there were 20 patients in the control groups made from individuals with normal pressure hydrocephalus. Thirty MS patients diagnosed with McDonald diagnostic criteria (2010) treated with methylprednisolone were included in this study. Data were stratified by the degree of severity in order to clarify the role of oxidative stress in the mechanisms of MS and to assess its potential as a biomarker. Thirty clinically definite RRMS patients were enrolled in this study. Levels of MDA, GSH, total antioxidant capacity TAC, GSH-Px and ROS, were determined in serum of the control group and RRMS patients in 7 days before MP (methylprednisolone) treatment and one month after MP treatment. Statistical analysis was performed with one-way analysis of variance (ANOVA), followed by LSD's post hoc tests., Key Messages: Oxidative stress precedes the inflammatory response in the multiple sclerosis patients. And methylprednisolone treatment can decrease brain antioxidant enzymes to reduce the neuroinflammatory attack., (© 2014 S. Karger AG, Basel)

The purpose of the present study was to investigate the effects and underlying mechanisms of diallyl sulfide (DAS), an organosulfur compound extracted from garlic, on drug-induced or chemical-induced liver injury caused by acetaminophen (APAP) or carbon tetrachloride (CCl4) in mice. DAS (100, 200, or 400 μmol kg−1) was orally administered 1 hour before APAP or CCl4 intraperitoneal injection, and the serum and liver tissue were collected 24 hours after APAP or CCl4 exposure. The serum aminotransferase activities and liver histopathological examination showed that DAS exhibited obvious hepatoprotective effects against acute liver injury induced by APAP or CCl4. In addition, exposure to APAP or CCl4 resulted in an increased content of malonaldehyde as well as a decreased ratio of reduced to oxidized glutathione, and a decreased level of superoxide dismutase and catalase activity in the liver (p < 0.05); however, pretreatment with DAS restored the perturbations of the antioxidant system in the liver. Beyond that, DAS pretreatment reduced the APAP-/CCl4-induced increase in phosphorylation of inhibitor of kappa B alpha (IκBα) and p65 subunit of nuclear factor kappa B (NF-κB) expression in the cytoplasm and nucleus in the liver. DAS pretreatment also decreased the excessive level of TNF-α caused by APAP or CCl4 in serum (p < 0.05). Moreover, DAS pretreatment regulated the expression of cleaved caspase 3, Bax and Bcl-2 in the liver and suppressed APAP-/CCl4-induced hepatocyte apoptosis. In conclusion, DAS exhibits hepatoprotective effects against drug-induced and chemical-induced liver injuries induced by APAP or CCl4 in mice, probably due to its ability to reduce hepatic oxidative stress and inhibit inflammatory injury and hepatocyte apoptosis. [ABSTRACT FROM AUTHOR]

Benzene is a well-known occupational and environmental toxicant associated with cytopenia, which is characterized by a disorder in the peripheral blood cell counts. However, no effective preventive strategy has been developed yet to tackle the exposure to benzene in daily life. The aim of this study was to evaluate the protective effects of diallyl trisulfide (DATS) on benzene-induced haematopoietic damage and to reveal its potential mechanisms of action. In our study, male Sprague-Dawley rats were divided into six groups. Rats were administered with benzene (1.3 g/kg BW by gavage) to establish the benzene poisoning model, while the DATS treatment groups were treated with benzene plus DATS (15 mg/kg, 30 mg/kg, 45 mg/kg, respectively, by gavage) for 28 days. Our results demonstrated that the counts of peripheral blood WBC and RBC decreased to 31.0% and 79.2%, respectively, in the benzene poisoning model group compared to the control. However, blood cell counts were restored by DATS treatment (30 mg/kg, 45 mg/kg). The apoptosis rates of peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs) were increased to 274% and 284%, respectively, following benzene exposure. Furthermore, expression levels of Bcl-2, PI3K and p -Akt were downregulated and those of Bax were upregulated in both cell types. Moreover, the oxidative parameters (oxygen species, malonaldehyde) were significantly increased, while the non-enzymatic GSH/GSSG ratios and the activities of enzymatic antioxidants (superoxide dismutase, glutathione peroxidase and catalase) were decreased. Interestingly, DATS treatment can restore the WBC number by 267.1% and 304.8% while RBC number by 108.6% and 117.7% in 30,45 mg/k DATS treated groups. In summary, we demonstrated that benzene-induced cytopenia was related to the apoptosis of PBMCs and BMCs, and DATS treatment could prevent benzene-induced cytopenia by suppressing oxidative stress-mediated cell apoptosis via the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Background & Aim: Diallyl trisulfide (DATS) has been verified to ameliorate hepatotoxicity induced by many drugs, but the protective actions of isoniazid (INH) and rifampicin (RFP) have not been reported. We attempted to elucidate the potential effects and mechanisms of DATS against INH&RFP-caused hepatotoxicity. Methods: Male Kunming mice weighing 18–22 g were divided into 6 groups. For the hepatic-protective study, DATS (10 mg per kg, 20 mg per kg, and 40 mg per kg bw, respectively) was orally administered two hours before the INH&RFP (100 mg per kg, 100 mg per kg bw, respectively) treatments. After 11 days of treatment, 10 mice in each group were taken for the carbon clearance test, while the other 10 mice were sacrificed for the collection of serum and livers for further measurements, including the levels of serum alanine aminotransferase (ALT), aspartate transaminase (AST) and total bilirubin (T.Bili), the liver index, and liver histopathological examination. Malondialdehyde (MDA), glutathione (GSH), and the level of interleukin 1-β (IL-1-β) were measured, the carbon clearance test was performed and the immunohistochemistry of F4/80 marker for activated Kupffer cells (KCs) was analyzed to investigate potential mechanisms. Results: DATS co-administration significantly inhibited the increase of liver index and elevation of serum ALT, AST and T.Bili levels induced by INH&RFP, as well as improved the hepatocellular structure. The further mechanistic studies demonstrated that DATS co-administration counteracted INH&RFP-induced oxidative stress in mice, which was illustrated by the restoration of GSH levels, and the reduction of MDA levels in the liver. Furthermore, DATS co-administration reactivated the KCs inhibited by INH&RFP, which was illustrated by the increase of carbon phagocytosis, and the restoration of the number of activated KCs and IL-1-β levels in the liver. Conclusion: DATS effectively protected the liver against INH&RFP-induced hepatotoxicity, which might be due to its antioxidant effect and enhancement of KCs' activities. [ABSTRACT FROM AUTHOR]

Context: Accumulating evidences have proposed the critical roles of oxidative stress in the etiology of lung injury caused by paraquat (PQ). Docosahexaenoic acid (DHA) is an essential n-3 polyunsaturated fatty acid (PUFA), which has been proved to possess prominent antioxidative and anti-inflammatory effects. Objective: The aim of this study was to evaluate effects of DHA against acute lung injury (ALI) induced by PQ in mice. Materials and methods: Male Kunming mice were randomly divided into three groups: control group, PQ group, and PQ+DHA group ( n = 24). The mice of PQ+DHA group received 500 mg/kg bodyweight DHA by gavage daily for consecutive 14 days. On day 8, the mice in PQ and PQ+DHA groups received a single oral dose of 50 mg/kg bodyweight PQ. All the mice were sacrificed on day 15. The myeloperoxidase (MPO) activities, levels of the malondialdehyde (MDA) and glutathione (GSH), and the 4-hydroxynonenal (4-HNE) and MDA modified proteins of lung were investigated. Results: DHA treatment significantly increased the survival rate of mice treated with PQ. Pulmonary MPO activities and MDA contents were elevated in the mice of the PQ group, while the GSH level was reduced. Furthermore, levels of 4-HNE and MDA modified protein in lungs of the PQ group mice were significantly increased. All the above changes were significantly inhibited by DHA pretreatment. Morphological examination revealed that DHA effectively attenuated the hyperemia, edema of ALI induced by PQ. Conclusion: These results demonstrated that DHA could effectively attenuate PQ-induced ALI in mice probably via its antioxidant activity. [ABSTRACT FROM AUTHOR]

Abstract: 1-Bromopropane (1-BP), an alternative to ozone-depleting solvents (ODS), exhibits central nervous system (CNS) toxicity in animals and humans. This study was designed to relate CNS damage by Morris water maze (MWM) test and oxidative stress to 1-BP exposure in the rat. Male Wistar rats were randomly divided into 4 groups (n =10), and treated with 0, 200, 400 and 800mg/kgbw 1-BP for consecutive 12 days, respectively. From day 8 to day 12 of the experiment, MWM test was employed to assess the cognitive function of rats. The cerebral cortex of rats was obtained immediately following the 24h after MWM test conclusion. Glutathione (GSH), oxidized glutathione (GSSG) and total thiol (total-SH) content, GSH reductase (GR) and GSH peroxidase (GSH-Px) activities, malondialdehyde (MDA) level, as well as 4-hydroxynonenal (4-HNE) and MDA modified proteins in homogenates of cerebral cortex were measured. The obtained results showed that 1-BP led to cognitive dysfunction of rats, which was evidenced by delayed escape latency time and swimming distances in MWM performance. GSH and total-SH content, GSH/GSSG ratio, GR activity significantly decreased in cerebral cortex of rats, coupling with the increase of MDA level. 4-HNE and MDA modified protein levels obviously elevated after 1-BP exposure. GSH-Px activities in cerebral cortex of rats also increased. These data suggested that 1-BP resulted in enhanced lipid peroxidation of brain, which might play an important role in CNS damage induced by 1-BP. [Copyright &y& Elsevier]

Oxidative stress is associated with the pathogenesis of carbon disulfide (CS 2 ) induced polyneuropathy. The nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in protecting cells against oxidative stress. However, whether there exists a Nrf2-mediated antioxidative machinery in CS 2 -induced neuropathy has not been elucidated. In the present study, male wistar rats were randomly divided into three experimental groups and one control group. The rats in experimental groups were treated with CS 2 by gavage at dosages of 200, 400 and 600 mg/kg/day respectively, six times per week for 6 weeks. Nrf2-keap1 antioxidative pathway and p62-related kinase signaling in rat nerve tissues was examined by western blotting and real-time PCR. The results demonstrated that CS 2 treatment resulted in Nrf2 translocation from the cytosol to the nucleus in rat spinal cords. In the meantime, the expression of antioxidative enzymes such as NAD(P)H quinone oxidoreductase-1, heme oxygenase-1, and glutamate-cysteine ligase was significantly increased. Furthermore, CS 2 treatment increased the level of p62 and its phosphorylation status, while decreased the level of keap1. In addition, CS 2 also lead to the activation of CAMKK2 and ULK1 kinase signaling in rat spinal cords and sciatic nerves. Taken together, our results indicated that CS 2 intoxication was associated with the activation of Nrf2-ARE antioxidative machinery, which might play a protective role against CS 2 -induced neuronal damage. [ABSTRACT FROM AUTHOR]

1-Bromopropane (1-BP) is used as a substitute for ozone-depleting solvents (ODS) in industrial applications. 1-BP could display central nervous system (CNS) neurotoxicity manifested by cognitive dysfunction. Neuroglobin (Ngb) is an endogenous neuroprotectant and is predominantly expressed in the nervous system. The present study aimed to investigate Ngb involvement in CNS neurotoxicity induced by 1-BP in rats. Male Wistar rats were randomly divided into 5 groups ( n =14) and treated with 0, 100, 200, 400 and 800 mg/kg bw 1-BP, respectively, by gavage for consecutive 12 days. Rats displayed cognitive dysfunction dose-dependently through Morris water maze (MWM) test. Significant neuron loss in layer 5 of the prelimbic cortex (PL) was observed. Moreover, 1-BP decreased Ngb protein level in cerebral cortex and Ngb decrease was significantly positively correlated with cognitive dysfunction. Glutathione (GSH) content, GSH/oxidized glutathione (GSSG) ratio and glutamate cysteine ligase (GCL) activity decreased in cerebral cortex, coupled with the increase in GSSG content. GSH and GSH/GSSG ratio decrease were significantly positively correlated with cortical Ngb decrease. Additionally, levels of N-epsilon-hexanoyl-lysine (HEL) and 4-hydroxy-2-nonenal (4-HNE) modified proteins in cerebral cortex of 1-BP-treated rats increased significantly. In conclusion, it was suggested that 1-BP resulted in decreased endogenous neuroprotectant Ngb in cerebral cortex, which might play an important role in CNS neurotoxicity induced by 1-BP and that 1-BP-induced oxidative stress in cerebral cortex might partly be responsible for Ngb decrease. [ABSTRACT FROM AUTHOR]