Sophocarpine Attenuates LPS-Induced Liver Injury and Improves Survival of Mice through Suppressing Oxidative Stress, Inflammation, and Apoptosis

Septic liver injury/failure that is mainly characterized by oxidative stress, inflammation, and apoptosis led to a great part of terminal liver pathology with limited effective intervention. Here, we used a lipopolysaccharide (LPS) stimulation model to simulate the septic liver injury and investigated the effect of sophocarpine on LPS-stimulated mice with endotoxemia. We found that sophocarpine increases the survival rate of mice and attenuates the LPS-induced liver injury, which is indicated by pathology and serum liver enzymes. Further research found that sophocarpine ameliorated hepatic oxidative stress indicators (H2O2, O2∙−, and NO) and enhanced the expression of antioxidant molecules such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). In addition, sophocarpine also attenuated regional and systematic inflammation and further reduced apoptosis of hepatocytes. Mechanistic evidence was also investigated in the present study as sophocarpine inhibited hepatic expression of the CYP2E/Nrf2 pathway during oxidative stress, inactivated p38/JNK cascade and NF-κB pathway, and, meanwhile, suppressed PI3K/AKT signaling that reduced apoptosis. Conclusively, the present study unveiled the protective role of sophocarpine in LPS-stimulated oxidative reaction, inflammation, and apoptosis by suppressing the CYP2E/Nrf2/ROS as well as PI3K/AKT pathways, suggesting its promising role in attenuating inflammation and liver injury of septic endotoxemia.

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Role of nitric oxide in hepatic microvascular injury elicited by acetaminophen in mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00217.2003 ◽

2004 ◽

Vol 286 (1) ◽

pp. G60-G67 ◽

Cited By ~ 48

Author(s):

Yoshiya Ito ◽

Edward R. Abril ◽

Nancy W. Bethea ◽

Robert S. McCuskey

Keyword(s):

Nitric Oxide ◽

Liver Injury ◽

Cell Injury ◽

Parenchymal Cell ◽

Protective Role ◽

Hepatic Expression ◽

Inos Inhibitor ◽

Microcirculatory Disturbances

Nitric oxide (NO) is suggested to play a role in liver injury elicited by acetaminophen (APAP). Hepatic microcirculatory dysfunction also is reported to contribute to the development of the injury. As a result, the role of NO in hepatic microcirculatory alterations in response to APAP was examined in mice by in vivo microscopy. A selective inducible NO synthase (iNOS) inhibitor,l- N6-(1-iminoethyl)-lysine (l-NIL), or a nonselective NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), was intraperitoneally administered to animals 10 min before APAP gavage. l-NIL suppressed raised alanine aminotransferase (ALT) values 6 h after APAP, whereas l-NAME increased those 1.7-fold. Increased ALT levels were associated with hepatic expression of iNOS. l-NIL, but not l-NAME, reduced the expression. APAP caused a reduction (20%) in the numbers of perfused sinusoids. l-NIL restored the sinusoidal perfusion, but l-NAME was ineffective. APAP increased the area occupied by infiltrated erythrocytes into the extrasinusoidal space. l-NIL tended to minimize this infiltration, whereas l-NAME further enhanced it. APAP caused an increase (1.5-fold) in Kupffer cell phagocytic activity. This activity in response to APAP was blunted by l-NIL, whereas l-NAME further elevated it. l-NIL suppressed APAP-induced decreases in hepatic glutathione levels. These results suggest that NO derived from iNOS contributes to APAP-induced parenchymal cell injury and hepatic microcirculatory disturbances. l-NIL exerts preventive effects on the liver injury partly by inhibiting APAP bioactivation. In contrast, NO derived from constitutive isoforms of NOS exerts a protective role in liver microcirculation against APAP intoxication and thereby minimizes liver injury.

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NEUROPROTECTIVE EFFECT OF WATERMELON (CITRULLUS LANATUS) PULP JUICE ON SCOPOLAMINE-INDUCED MEMORY DEFICITS IN SWISS ALBINO MICE: THE ROLE OF ACETYLCHOLINESTERASE AND OXIDATIVE STRESS

International Journal of Research in Ayurveda and Pharmacy ◽

10.7897/2277-4343.120373 ◽

2021 ◽

Vol 12 (3) ◽

pp. 52-56

Author(s):

Divya N ◽

Amudha P ◽

Viveka K Priya

Keyword(s):

Oxidative Stress ◽

Ache Activity ◽

Citrullus Lanatus ◽

Neuroprotective Effect ◽

Memory Deficits ◽

Memory Deficit ◽

Stress Indicators ◽

Oxidative Stress Indicators ◽

And Oxidative Stress

The effect of Watermelon (Citrullus lanatus) Pulp Juice (WPJ) on scopolamine (SCOP) induced memory deficits is due to the involvement of oxidative stress and AChE activity. The juice was obtained by crushing the pulp in blender and three different concentrations of 100%, 50% and 25% was administration to prevent memory deficit by evaluating changes of AChE activity and oxidative stress indicators (SOD, CAT, LPO and GPx) induced by scopolamine. These results provide evidence that WPJ is an alternative to protect SCOP induced memory deficits in mice by involvement of oxidative stress and AChE activity.

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Irisin Improves Autophagy of Aged Hepatocytes via Increasing Telomerase Activity in Liver Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/6946037 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13 ◽

Cited By ~ 8

Author(s):

Jianbin Bi ◽

Lifei Yang ◽

Tao Wang ◽

Jia Zhang ◽

Teng Li ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Mitochondrial Function ◽

Ischemia Reperfusion ◽

The Elderly ◽

Telomerase Activity ◽

Protective Role ◽

Primary Hepatocytes ◽

Old Rats

An aged liver has decreased reparative capacity during ischemia-reperfusion (IR) injury. A recent study showed that plasma irisin levels predict telomere length in healthy adults. The aim of the present study is to clarify the role of irisin, telomerase activity, and autophagy during hepatic IR in the elderly. To study this, hepatic IR was established in 22-month- and 3-month-old rats and primary hepatocytes were isolated. The results showed that the old rats exhibited more serious liver injury and lower levels of irisin expression, telomerase activity, autophagy ability, and mitochondrial function than young rats during hepatic IR. Irisin activated autophagy and improved mitochondrial function via increasing telomerase activity in aged hepatocytes. Inhibition of telomerase activity by BIBP1532 abolished the protective role of irisin in hepatocytes during hypoxia and reoxygenation. Additionally, this study proved irisin increased the telomerase activity via inhibition of the phosphorylation of JNK during hepatic IR. Administration of exogenous irisin significantly mitigated the inflammation, oxidative stress, apoptosis, and liver injury in an old rat model of hepatic IR. In conclusion, irisin improves autophagy of aged hepatocytes via increasing telomerase activity in hepatic IR. Irisin exhibits conspicuous benefits in increasing reparative capacity of an aged liver during hepatic IR.

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The Beneficial Use of Melanin in Inhibiting and Treating HCC Through Preventing CBC, Liver Enzymes, Oxidative Stress, and Lipid Peroxidation Alterations

10.21203/rs.3.rs-40619/v1 ◽

2020 ◽

Author(s):

Mohamed Anwar K Abdelhalim ◽

Yanallah H Al-Mohy ◽

Mohammed S Al-Ayed

Keyword(s):

Oxidative Stress ◽

Blood Cells ◽

Liver Enzymes ◽

White Blood Cells ◽

Blood Parameters ◽

Stress Indicators ◽

Beneficial Use ◽

Liver Cancers ◽

Oxidative Stress Indicators

Abstract Hepatocellular carcinoma (HCC) accounts for more than 90% of primary liver cancers and is a major global health problem. The present application relates to normalizing abnormal levels of hematological blood parameters, oxidative stress indicators, and liver enzyme levels in the rats using melanin, and particularly, to treating their abnormal levels, in addition to evaluate the role of melanin during and after the progression of HCC, which will be supplemented histologically. Hematological blood parameters such as white blood cells (WBCs), red blood cells (RBCs), hemoglobin (HGB), hematocrit (HCT), and platelets (PLTs); liver enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST); oxidative stress such as glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD); LP malondialdehyde (MDA) were evaluated in all groups of rats. Injection of Diethylnitrosamine (DEN) and 2-Acetyaminofluorine (2-AFF) induced HCC in the rats accompanied with a significant reduction in WBCs, RBCs, HGB, HCT, and PLTs, GSH-PX, and SOD; while a significant elevation was observed in ALT and AST, and MDA compared to the control. Melanin normalized all the above mentioned parameters during and after the progression of cancer towards their control values. These results demonstrate the beneficial use of melanin as a powerful antioxidant tool in inhibiting and treating HCC in the rats.

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Role of Oxidative Stress Indicators in Development of Chronic Kidney Disease in Patients with Type 2 Diabetes

Experimental and Clinical Physiology and Biochemistry ◽

10.25040/ecpb2017.04.057 ◽

2017 ◽

Vol 2017 (4) ◽

pp. 57-60

Author(s):

D. KUTSYK ◽

◽

E. SKLYAROV ◽

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Stress Indicators ◽

Oxidative Stress Indicators

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Protective Role of Terminalia bellirica (Gaertn.) Roxb Fruits Against CCl4 Induced Oxidative Stress and Liver Injury in Rodent Model

Indian Journal of Clinical Biochemistry ◽

10.1007/s12291-017-0732-8 ◽

2018 ◽

Vol 34 (2) ◽

pp. 155-163 ◽

Cited By ~ 3

Author(s):

Kuriakose Jayesh ◽

Lal Raisa Helen ◽

A. Vysakh ◽

Eldhose Binil ◽

M. S. Latha

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Protective Role ◽

Rodent Model ◽

Terminalia Bellirica

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Oxidative stress and low molecular weight antioxidants in triticale shoots under chloride salinization

Butlerov Communications ◽

10.37952/roi-jbc-01/20-62-6-125 ◽

2020 ◽

Vol 62 (6) ◽

pp. 125-130

Author(s):

Viktor V. Ivanishchev ◽

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Molecular Weight ◽

Ascorbic Acid ◽

Correlation Coefficients ◽

Low Molecular Weight ◽

Stress Indicators ◽

Sodium Chloride Stress ◽

Oxidative Stress Indicators

We studied the alterations in oxidative stress indicators (hydrogen peroxide, superoxide radical, lipid peroxidation – LPO) and the alterations in the content of low molecular weight metabolites (ascorbic acid, glutathione, proline, chlorophyll and carotenoids) in the shoots of triticale (Triticosecale) under short-term (0-96 h) sodium chloride stress (120 mM) with statistical methods: principal component analysis (PCA) and cluster analysis. An analysis of the alterations in oxidative stress indicators allowed us to calculate the correlation coefficients for the pairs: peroxide – superoxide (0.52), peroxide – LPO (0.62), superoxide – LPO (0.23). The inclusion in the analysis of data on alterations in the content of low molecular weight antioxidants showed that the PCA method forms three main groups for all the studied characteristics: (1) LPO and hydrogen peroxide, (2) chlorophyll and carotenoids, (3) glutathione and ascorbate. The correlation coefficients were calculated for pairs: ascorbate – glutathione (0.71), ascorbate – proline (0.81), glutathione – proline (0.28). Such a value of the coefficient of the first pair suggests that ascorbic acid also performs numerous other functions, in addition to participating in the ascorbate-glutathione cycle. The high correlation between ascorbate and proline can be explained by the similar nature of alterations in their content in triticale shoots under conditions of short-term sodium chloride stress. Negative correlation coefficients in pairs of hydrogen peroxide – chlorophyll (-0.73), peroxide – carotenoids (-0.75), ascorbic acid – LPO (-0.70), LPO – proline (-0.69) give reason to talk about the possible protective role of photosynthesis pigments from accumulating hydrogen peroxide, as well as the potential role of ascorbic acid and proline in protecting membranes from lipid peroxidation. The application of the cluster analysis method showed that first and second order clusters between ascorbate, proline and glutathione reflect their known antioxidant role. The results obtained may also indicate that pigments have a much lower protective function.

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