Liver Tissue Malondialdehyde Research Articles

Magnesium isoglycyrrhizinate alleviates liver injury in obese rats with acute necrotizing pancreatitis

ObjectiveFor patients with acute necrotizing pancreatitis (ANP), a high body mass index (BMI) increases the likelihood of acute hepatic injury (AHI). In the current study, we explored whether magnesium isoglycyrrhizinate (MgIg) could alleviate ANP-induced liver injury in obese rats. MethodsSprague-Dawley (SD) rats were selected for the present study, and the ANP model was established by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. Thirty-six SD rats were randomly assigned to six groups: the normal (N), standard rat chow (SRC) normal (SN), SRC ANP (S-ANP), high-fat diet (HFD) normal (H–N), HFD ANP (H-ANP), and MgIg pretreatment HFD ANP (H-ANPT) groups. The rats in the H-ANPT group were treated with MgIg (30 mg/kg) intragastrically for 7 days before the ANP model was established. The rats were sacrificed 12 h after ANP was established, and the blood and pancreatic and liver tissues were collected. Differences in the physiology, pathology and cellular and molecular responses of the rats in each group were examined. ResultAnalyses of serum amylase lipase, alanine aminotransferase and aspartate aminotransferase indicated that obesity aggravated ANP-induced hepatic injury and that MgIg improved liver function. The superoxide dismutase, malondialdehyde, M1 macrophage, M2 macrophage, neutrophil, NF-κB, IL-1β and caspase-3 levels in liver tissue showed that MgIg attenuated H-ANP-induced hepatic injury by inhibiting oxidative stress and inflammation. ConclusionObesity aggravated ANP-induced liver injury via oxidative stress and inflammatory reactions. MgIg alleviated oxidative stress and decreased the inflammatory reaction, protecting the liver against the AHI induced by ANP in obese rats.

Protective Effects of β-Carotene Against Ammonium Sulfate Toxicity: Biochemical and Histopathological Approach in Mice Model

In this study, the protective role of β-carotene against ammonium sulfate-induced toxicity has been evaluated in Mus musculus var. albino mice, along with biochemical and histopathological parameters. Some biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), creatinine and oxidative stress parameters, malondialdehyde (MDA), and glutathione (GSH) levels in kidney and liver tissues were investigated. The mice were randomly divided into six groups. Group I received intraperitoneal injections of 0.9% NaCl; group II received orally administered 250 mg kg-1 bw β-carotene, group III received orally administered 500 mg kg-1 bw β-carotene; group IV received 320 mg kg-1 bw ammonium sulfate; group V was given 250 mg kg-1 bw β-carotene +320 mg kg-1 of bw ammonium sulfate; and group VI received orally administered 500 mg kg-1 of bw β-carotene +320 mg kg-1 of bw ammonium sulfate. As a result, it was determined that the ammonium sulfate treatment causes significant changes in the biochemical and oxidative stress parameters and also in histological examinations. In group IV, significant increases in ALT, AST, BUN, MDA, and creatinine levels, and a significant decrease in GSH levels were observed compared with control group. In histopathological examinations, different pathological findings such as proteinaceous deposits, thickening of basement membrane, hyaline cast in kidney tissue and stellate cell, karyomegaly, and binucleated cells in liver tissue were observed. β-carotene treatment in group V and VI ameliorated the elevated levels of liver enzymes and improved oxidative stress and histopathological findings, and so, it could be concluded that β-carotene offered remarkable protection against ammonium sulfate-induced toxicity.

Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation.

Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.

Antioxidant effect of lactoferrin on rat liver injury induced by diazinon

This study is done to evaluate the antioxidant effect of Lactoferrin (LF) on liver injury induced byDiazinon (DZN). Seventy five rats were divided into five groups, each group contains 15 rats;control (G1): (no treatments), Lactoferrin (G2): (LF, 100 mg/kg bw orally daily for 6 weeks),diazinon (G3): (DZN, 70 mg/kg bw orally, daily for 4 weeks), DZN +LF (G4): (DZN, 70 mg/kg bworally, daily for 4 weeks followed by LF, 100 mg/kg bw orally daily for 2 weeks, and (LF +DZN)group (G5): (LF, 100 mg/kg bw orally daily for seven weeks and DZN, 70 mg/kg bw for fourweeks only started at the second week of the experiment). Nitric oxide (NO), Malondialdehyde(MDA), and glutathione peroxidise (GSH-Px) were estimated in liver tissue, in addition to liversections were taken for histopathological examination. In comparison to control group (P < 0.005),NO and MDA in liver tissue were increased significantly, while GSH-Px activities weresignificantly decreased in DZN group. In LF group NO, MDA levels were significantly decreased(P < 0.05), and GSH-Px activities were significantly increased. Compared to DZN group (P <0.001), NO and MDA, in liver homogenate were found decreased significantly in both (DZN+LF)and (LF+DZN) groups, and GSH-Px activities were significantly increased. Histopathologicalchanges in liver tissue induced by DZN were: mild fibrosis with vacular degeneration ofhepatocyte, preductal mononeuclear leucocytic cellular infiltrations, and disarrangement of normalhepatic cells with congestion of portal blood vessels. Rats received LF after intoxicated with DZN(DZN+LF group) showed only normal lobular architecture and normal hepatic cells, meanwhile(LF+DZN group) showed: Von kupffer cells proliferation with mild dialatation of central vein.

Significance of selected biochemical markers in predicting the outcome of schistosomiasis

This study aimed to correlate the histopathological changes in mice liver with alterations either in liver tissue antioxidants enzymes (catalase and reduced glutathione (GSH)), oxidative stress marker (malondialdehyde (MDA)) or in serum liver function parameters (Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (T.P.) and albumin) to predict the outcome of schistosomiasis. Fourty male Swiss albino mice were used in this study and infected with Schistosoma mansoni for 2, 4, 6 and 8 weeks (8 mice for each group), while, the uninfected mice were used as negative control. Liver tissue antioxidants enzymes, oxidative stress marker and serum liver function parameters were determined in coincide with the liver tissue histopathological changes. All selected biochemical makers showed a strong significant positive correlation (p &lt; 0.05) with liver histopathology score except serum albumin and liver tissue catalase enzyme. The last two parameters exhibited negative correlation with liver histopathology score. These results revealed that the more increase in the level of AST, ALT, T.P. and globulin in serum or liver tissue MDA and GSH indicating severs histopathological changed into the affected liver and hopeless prognosis is expected. On contrary, the increase in albumin level in serum or catalase level in liver tissue of affected patient/animal demonstrating mild liver histopathological changes. Subsequently, good prognosis and response to anti-schistosomal treatment will be predictable. This study opens the way to predict the outcome of schistosomiasis through easy and rapid biochemical test. Therefore, other studies are required to apply such correlation with other biochemical parameters especially that synthesized into the liver.

Effects of the Administration of Thyroid Hormones in Cases of Hepatic Ischemia and Reperfusion Injury

Objective: Hepatic ischemia and reperfusion (IR) injury is the most important cause of cellular death and hepatic dysfunction following liver transplantation and resection. Our aim in this study is to reveal the early stage effects of thyroid hormone levels on hepatic IR injury that effectively act on cellular homeostasis. Methods: Forty-six male Wistar albino rats were divided into 6 groups as follows: euthyroid-sham (n = 8), euthyroid with IR injury (n = 8), hyperthyroid-sham (n = 7), hyperthyroid with IR injury (n = 7), hypothyroid-sham (n = 8), and hypothyroid with IR injury (n = 8). After 90 minutes of partial hepatic ischemia, 90 minutes of reperfusion was applied. Liver tissue malondialdehyde (MDA) levels, catalase (CAT), glutathion peroxidase, and superoxide dismutase (SOD) enzyme activities were measured. Hepatic tissue was immunohistochemically analyzed. Results: MDA levels of liver tissue were analyzed, and hepatic MDA levels in the hyper-IR group were found to be significantly lower (P = 0.002) than those of the hypo-IR and euthyroid-IR groups. Serum CAT levels did not differ between control groups, whereas CAT values in the hyper-IR group were detected to be significantly lower than in the euthyroid-IR and hypothyroid-IR groups (P = 0.003). However, levels of SOD and glutathione peroxidase (GPX) were not affected by the functional state of the thyroid. No statistically significant difference was seen in the results of the histopathologic evaluation and immunohistochemical staining of the liver tissue. Conclusion: The administration of thyroid hormone within a short time before IR injury may have protective effects.

Short Communication: Hepatoprotective effect of methanol extract of sambiloto leaves (Andrographis paniculata) against malondialdehyde levels in liver tissues of paracetamol-induced Wistar rat

Andriani, Suseno G, Effiana, Novriany V, Fitrianingrum I. 2018. Short Communication: Hepatoprotective effect of methanol extract of sambiloto leaves (Andrographis paniculata) against malondialdehyde levels in liver tissues of paracetamol-induced Wistar rat. Nusantara Bioscience 10: 87-90. Andrographis paniculata contains andrographolide and flavonoids, which have a hepatoprotective effect. This study was aimed to examine hepatoprotective effect of Andrographis paniculata extract against liver tissues malondialdehyde (MDA) levels of paracetamol induced Wistar rat (Rattus novegicus). The study was designed with posttest-only control group conducted at Tanjungpura University, Indonesia in June 2015. A total of 30 rats at age of three weeks were divided into 6 groups. They were given toxic dose paracetamol, curcumin and A. paniculata extract in different dose. Liver tissues were tested by Wills’s method. The data was analyzed using One-way ANOVA and LSD Post-hoc test. MDA levels of liver tissues were i.e, normal control (0.34 nmol mL-1), positive control (0.34 nmol mL-1), dose 1 (0.45 nmol mL-1), dose 2 (0.55 nmol mL-1), dose 3 (0.63 nmol mL- 1 ), negative control (1.32 nmol mL-1). Result showed that MDA levels of liver tissues of negative control group were significantly different with other groups (ANOVA, p≤ 0.05). There were no significant differences between MDA levels of liver tissues of Dose 1 with normal control and positive control (ANOVA, p&gt;0.05). The methanol extract of A. paniculata has a hepatoprotective effect in (MDA) levels of paracetamol-induced Rattus novegicus with an effective dose of 500 mg kg-1.

EFFECTS OF FEEDING GENETICALLY MODIFIED (GM) MAIZE ON OXIDATIVE STRESS PARAMETERS IN NEW ZEALAND RABBIT

In this study, we investigated the effects of Genetically Modified (GM) Maize on liver and kidney tissue weights, malondialdehyde (MDA) and glutathione (GSH) levels of liver and kidney tissues in New Zealand Rabbits. For this purpose, rabbits were divided into three groups: parental, first-generation and second-generation. Each group was divided into two sub-groups i.e. control group and the treatment group. Rabbits on the control group were fed with conventional maize (non-GM), whereas rabbits which are in the treatment groups were fed with GM maize. Six females and six male New Zealand rabbits were used per group. At the end of the experimental period, tissue samples were taken and tissue weights, MDA and GSH levels were determined. Overall, as the generations progressed, a statistically significant increase in liver weights and a decrease in kidney weights were observed. There was no statistically significant change as regards MDA and GSH levels of liver and kidney tissues of groups without GM maize inclusion in the diet. However in all three-generation of GM maize treated groups, there was a significant decrease in GSH levels and a significant increase in MDA levels were observed.

Phytochemical Analysis and Evaluation of the Antioxidant, Anti-Inflammatory, and Antinociceptive Potential of Phlorotannin-Rich Fractions from Three Mediterranean Brown Seaweeds.

Phlorotannins, phenolic compounds produced exclusively by seaweeds, have been reported to possess various pharmacological properties. However, there have been few works on these compounds from Mediterranean seaweeds. In this study, we investigated the phytochemical analysis and pharmacological potential of phlorotannin-rich fractions from three brown seaweeds collected along the Tunisia coast: Cystoseira sedoides (PHT-SED), Cladostephus spongeosis (PHT-CLAD), and Padina pavonica (PHT-PAD). Phytochemical determinations showed considerable differences in total phenolic content (TPC) and phlorotannin content (PHT). The highest TPC level (26.45mgPGE/g dry material (Dm)) and PHT level (873.14μgPGE/g Dm) were observed in C. sedoides. The antioxidant properties of these three fractions assessed by three different methods indicated that C. sedoides displayed the highest total antioxidant activity among the three species (71.30mgGAE/g Dm), as well as the free radical scavenging activity with the lowest IC50 value in both DPPH (27.7μg/mL) and ABTS (19.1μg/mL) assays. Furthermore, the pharmacological screening of the anti-inflammatory potential of these fractions using in vivo models, in comparison to reference drugs, established a remarkable activity of PHT-SED at the dose of 100mg/kg; the inhibition percentages of ear edema in mice model and paw edema in rats model were of 82.55 and 81.08%, respectively. The content of malondialdehyde (MDA) in liver tissues has been quantified, and PHT-SED was found to remarkably increase the lipid peroxidation in rat liver tissues. In addition, in two pain mice models, PHT-SED displayed a profound antinociceptive activity at 100mg/kg and has proved a better analgesic activity when used in combination with the opioid drug, tramadol.

Protective Effect of JXT Ethanol Extract on Radiation-Induced Hematopoietic Alteration and Oxidative Stress in the Liver.

This study aims at investigating the radioprotective effect of ethanol extract from Ji-Xue-Teng (JXT, Spatholobus suberectus) on radiation-induced hematopoietic alteration and oxidative stress in the liver. Mice were exposed to a single acute γ-radiation for the whole body at the dose of 6.0 Gy, then subjected to administration of amifostine (45 mg/kg) or JXT (40 g crude drug/kg) once a day for 28 consecutive days, respectively. Bone marrow cells and hemogram including white cells, red cells, platelet counts, and hemoglobin level were examined. The protein expression levels of pJAK2/JAK2, pSTAT5a/STAT5a, pSTAT5b/STAT5b, and Bcl-2 in bone marrow tissue; levels of reactive oxygen species (ROS); and the activity of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum and liver tissue were determined. At the end of the experiment, the effect of JXT on cell viability and G-CSF and G-CSFR levels in NFS-60 cells were tested by CCK-8 assay, ELISA, and flow cytometry. The results showed that the mice exposed to γ-radiation alone exhibited a typical hematopoietic syndrome. In contrast, at the end of the 28-day experiment, irradiated mice subjected to oral administration of JXT showed an obvious improvement on blood profile with reduced leucopenia, thrombocytopenia (platelet counts), RBC, and hemoglobin levels, as well as bone marrow cells. The expression of pJAK2/JAK2, pSTAT5a/STAT5a, and Bcl-2 in bone marrow tissue was increased after JXT treatment. The elevation of ROS was due to radiation-induced toxicity, but JXT significantly reduced the ROS level in serum and liver tissue, elevated endogenous SOD and GSH-PX levels, and reduced the MDA level in the liver. JXT could also increase cell viability and G-CSFR level in NFS-60 cells, which was similar to exogenous G-CSF. Our findings suggested that oral administration of JXT effectively facilitated the recovery of hematopoietic bone marrow damage and oxidative stress of the mice induced by γ-radiation.

CdS nanoparticles of different lengths induce differential responses in some of the liver functions of mice.

Cadmium sulfide nanoparticles (CdS NPs) are one of important nanoparticle materials which are widely used in photoelectric production, but their potential health hazard to the liver is not clear. This study is aimed at exploring the possible mechanisms of liver injury induced by CdS NPs. Male mice were treated with nanoparticles of 110-130 nm and 80-100 nm cadmium sulfide. The main methods were based on detecting the vigor of superoxide dismutase (SOD) and glutathione (GSH), and content of malondialdehyde (MDA) in both blood and liver tissues as well as on observing the pathological changes in liver tissue. CdS NPs suppressed the activity of SOD and GSH, and increased the serum MDA content (p < 0.05); both effects were observed together in liver tissues of 80-100 nm group (p < 0.05) and were accompanied by an obviously inflammatory response. CdS NPs induced oxidative damage and inflammatory response in liver tissue, which may be an underlying mechanism for its pulmonary toxicity. Additionally, the toxicity of CdS NPs was closely related to the size of nanoparticles. Pathological results showed that the hepatotoxicity of shorter CdS NPs is greater than that of longer CdS NPs (Tab. 6, Fig. 3, Ref. 20).

The therapeutic effects of thalidomide and etanercept on septic rats exposed to lipopolysaccharide.

The aim of this study was to evaluate the therapeutic effects of thalidomide and etanercept on lipopolysaccharide (LPS)-induced sepsis in a rat model. Thirty male Wistar Albino rats were divided into 5 groups: Control, LPS, LPS+Thalidomide, LPS+Etanercept, and LPS+Thalidomide+Etanercept. The control group was given a 1 mL intraperitoneal (i.p.) injection of 0.9% saline solution. For endotoxic treatment, the rats were injected with a single i.p. dose of LPS (Escherichia coli 0111: B4 (5 mg/kg). Thalidomide (0.5 mg/kg) and etanercept (1 mg/kg) were administered i.p. to the therapeutic groups. Hepatic tissue tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and platelet-derived growth factor (PDGF) levels were determined by enzyme-linked immunosorbent assay and malondialdehyde (MDA) levels and total oxidant status (TOS) were measured using appropriate methods. In vivo results exhibited elevated liver tissue TNF-α, IL-6, ICAM-1, PDGF, MDA, and TOS levels in the LPS-treated animals compared with the controls. The analysis of liver tissue supported the findings of biochemical alterations and indicated a therapeutic role for thalidomide and etanercept. Treatment of septic animals with these agents resulted in a remarkable decrease in the selected proinflammatory cytokines, angiogenic factors, and reactive oxygen parameters. Restoration of cytokine balance and oxidant status to normal levels following treatment with selected therapeutic agents suggests that thalidomide and etanercept can help to avoid the potentially devastating effects of sepsis.

The Effect of a period of high intensive interval training on total antioxidant capacity and level of liver tissue malondialdehyde in male Wistar rats

The Effect of a period of high intensive interval training on total antioxidant capacity and level of liver tissue malondialdehyde in male Wistar rats

Effects of three different concentrations of hypertonic sodium salt resuscitation on liver injury of rats at the early stage of severe burned

To investigate the effects of three different concentrations of hypertonic sodium salt (HS) resuscitation on liver injury of rats at the early stage of severe burned. 104 female Sprage-Dawley (SD) rats were randomly divided into five groups: sham group (n = 8), lactated Ringer solution (LR) group (n = 24), 600, 800, 1 000 mmol/L HS groups (HS600, HS800, and HS1000 groups, n = 24). Rats in LR group and HS groups were subjected to full-thickness scald with 30% total body surface area (TBSA), and then given liquid resuscitation treatment with LR and the corresponding HS. These rats were sacrificed at 2, 8 and 24 hours post injury to collect blood and liver tissue. Rats in sham group were given simulation of burns without resuscitation, which were immediately sacrificed and the specimens were harvested. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by automatic biochemical analyzer. The levels of liver tissue malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by ultraviolet spectrophotometry. The expression of liver tissue p38 mitogen-actirated protein kinase (p38MARK) was detected by Western Blot. Compared with sham group, the levels of ALT, AST, MDA and p38MAPK were increased, and the activities of SOD were decreased in LR group and different degrees in HS groups at each time point after injury. Compared with LR group, the levels of ALT, AST, MDA and p38MAPK were decreased and the activities of SOD were increased in different degrees with HS groups, among which HS600 group changed most significantly [ALT (U/L): 147±52 vs. 227±60 at 8 hours, 138±47 vs. 191±41 at 24 hours; AST (U/L): 288±79 vs. 548±237 at 2 hours, 567±167 vs. 841±338 at 8 hours, 515±180 vs. 712±159 at 24 hours; MDA (nmol/mg): 0.287±0.036 vs. 0.395±0.041 at 2 hours, 0.298±0.030 vs. 0.392±0.018 at 8 hours, 0.278±0.033 vs. 0.422±0.036 at 24 hours; SOD (U/mg): 230±16 vs. 159±30 at 2 hours, 251±14 vs. 194±15 at 8 hours, 296±8 vs. 243±11 at 24 hours; p-p38MAPK/p38MAPK (A value): 0.778±0.040 vs. 1.065±0.066 at 2 hours, 0.791±0.046 vs. 0.967±0.041 at 8 hours, 0.733±0.027 vs. 1.020±0.043 at 24 hours; all P < 0.05]. The levels of ALT and AST in HS600 group were significantly lower than those in HS1000 group at 2 hours and in HS800 group at 8 hours. The levels of MDA and p38MAPK in HS600 group were significantly lower than those of HS800 group and HS1000 group, and the level of SOD in HS600 group was significantly higher than that in HS800 group and HS1000 group at each time point after injury. There were no significant differences in all test indicators between HS800 group and HS1000 group at each time point after injury. High concentration of HS can reduce the early liver injury in severely scalded rats, of which the curative effect of HS 600 mmol/L is best.

Protective effect of rimonabant, a canabinoid receptor 1 antagonist, on nonalcoholic fatty liver disease in a rat model through modulation of the hepatic expression of activin A and follistatin.

Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality, and there is still no proven effective therapy. The endocannabinoid system plays an important role in various liver diseases. Activin A is a member of the transforming growth factor beta (TGF-β) superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin A. This study was designed to investigate the effect of rimonabant (a potent cannabinoid receptor1 (CB1) antagonist) on NAFLD induced with a choline-deficient (CD) diet in rats, as well as to detect whether it can alter the hepatic expression of activin A and follistatin. Forty rats were distributed among 4 groups: the control group, the rimonabant treatment group (normal rats that received rimonabant); the CD diet group (NAFLD induced with a CD diet); and the CD diet + rimonabant group (NAFLD treated with rimonabant). It was found that the CD diet caused significant increase in liver index, serum levels of liver enzymes, malondialdehyde (MDA), TGF-β1, activin A, and CB1 expression in liver tissue, with a significant decrease in glutathione peroxidase (GSH-Px) and follistatin mRNA expression in liver tissues. The administration of rimonabant significantly improved all of the studied parameters compared with the group fed the CD diet alone. Histopathological examination supported these results. We concluded that rimonabant significantly counteracted NAFLD induced with the CD diet by decreasing oxidative stress and hepatic expression of TGF-β1, and modulating the hepatic expression of activin A and follistatin.

Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats.

The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC. subsp. plicatum ethanol extract (HPE) against gentamicin-induced nephrotoxicity. Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material. They were formed into six groups containing 6 rats each and were allowed to adapt to laboratory conditions for 7 d. Group I: control, 5% DMSO intraperitoneal (i.p.); Group II: HPE 100 mg/(kg·d) i.p.; Group III: HPE 200 mg/(kg·d) i.p.; Group IV: gentamicin as 80 mg/(kg·d) i.p.; Group V: gentamicin as 80 mg/(kg·d) i.p.+HPE 100 mg/(kg·d) i.p.; and Group VI: gentamicin as 80 mg/(kg·d) i.p.+HPE 200 mg/(kg·d) i.p. for 8 d. Following treatment, serum, liver, and kidney tissues were used to assess blood urea nitrogen (BUN), creatinine, enzymatic and non-enzymatic antioxidants, and lipid peroxidation. Gentamicin significantly increased serum BUN, creatinin, and liver and kidney levels of malondialdehyde (MDA). It also decreased the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin, liver and kidney oxidant marker, and tubular necrosis as well as by an increase in antioxidant enzymes. It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats. As a result, these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.

Protective effect of alcohol extract of Yulangsan leaf on chemically-induced liver injury in mice

Purpose: To investigate the protective effect of Millettia pulchra Kurz var. Laxior (Dunn) Z. Wei (Yulangsan) leaf (YLSL) on chemically-induced liver injury in mice.Methods: Models of carbon tetrachloride (CCl4) and D-galactosamine (D-GalN)-induced liver injury in Kunming mice were prepared by intraperitoneal injection. Sixty mice were randomly divided into normal saline (NS) group, liver-injury group, low-, medium- and high-dose YLSL groups (7.5, 15 and 30 g/kg dose, respectively), and biphenyldicarboxylate (BPDC) group, with 10 animals per group. Indices for liver, spleen and thymus were assessed. Serum aspartate transaminase (AST) and alanine aminotransferase (ALT) activities, levels of malondialdehyde (MDA) in liver tissues and reduced glutathione (GSH) as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver tissue were assayed. Liver tissue damage was assessed histologically.Results: YLSL could significantly decrease the elevation of AST or ALT in liver injuries induced by CCl4 or D-GalN in mice, which showed a dose-effect relationship obviously. The high dose YLSL significantly decreased thymus weight relative to CCl4 and D-GalN (CCL4 CCL4+YLSL: 4.4213 ± 1.0544 vs 3.7120 ± 0.8534; D-GalN vs YLSL + D-GalN: 3.7272 ± 1.1655 vs 1.9548 ± 1.2996, p &lt; 0.01). However, SOD activity was significantly increased (p &lt; 0.01, p &lt; 0.05). In treatment groups exposed to CCl4, GSH-Px activity was significantly increased (p &lt; 0.01) and GSH levels decreased (middle dose group and positive control group). In treatment groups with D-GalN, GSH content was significantly increased (p &lt; 0.01 or p &lt; 0.05), while GSH-Px activity decreased (p &lt;0.01).Conclusion: YLSL has protective effect against chemically-induced liver injury in mice. The mechanism may be related to attenuation of free radical-induced lipid peroxidation.Keywords: Millettia pulchra, Liver injury, Biochemical parameters, Thymus, Antioxidant, Dgalactosamine, Biphenyldicarboxylate

Protective effect of propofol preconditioning on ischemia-reperfusion injury in human hepatocyte.

Blood reperfusion after ischemia is the main measure to restore cell function. This study was aimed to explore the effect of propofol on rat and cell models of liver ischemia-reperfusion (I/R) injury, and to investigate its possible mechanism. Wistar rats were divided into four groups: control group, sham group, I/R group, and propofol group. Human hepatocyte HL7702 was divided into six groups: control group, I/R group and propofol (5, 10, 20 and 40 µmol/L) groups. After the animal and cell models were established, the alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and adenosine triphosphate (ATP) levels in liver tissues and hepatocytes were measured. Cell viability and apoptosis of hepatocytes were respectively determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. Furthermore, the expressions of apoptosis-related proteins in hepatocytes were determined by Western blot analysis. ALT, AST and MDA levels were all decreased significantly, and the ATP level was increased significantly in propofol group compared with that in I/R group in both liver tissues and hepatocytes. Additionally, cell viability of hepatocytes in propofol group was higher than that in I/R group, while the percentage of apoptotic cells in propofol group was less than that in I/R group. Moreover, the expression of caspase-3 decreased and the expression of Bcl-2 increased significantly after propofol preconditioning. Our findings suggested that propofol preconditioning might be an effective strategy for protecting the liver from I/R injury, which might provide a scientific basis for clinical application.

L-carnitine alleviates liver warm ischemia-reperfusion injury in rats through activating Nrf2/HO-1 pathway

Objective To investigate the protective effects of L-carnitine on liver warm ischemia-reperfusion injury (WIRI) in rats and to explore its possible role of L-carnitine in affecting Nrf2/HO-1 pathway. Methods Twenty-four male Sprague-Dawley (SD) rats were randomly divided into three groups including sham-operated (SO) group, liver warm ischemia and reperfusion (WIR) group and L-carnitine pretreatment (LC) group. L-carnitine was injected intraperitoneally in LC group while the equal volume of saline was injected in SO group and WIR group. The levels of ALT and AST in serum as well as the activities of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in liver tissues were detected. Meanwhile, pathologic change of liver tissue was observed. And then, the mRNA expression of NF-E2-related factor 2(Nrf2) and heme oxygenase 1(HO-1) in liver tissues was determined. Results Compared with the SO group, ALT and AST level in serum were significantly increased (P<0.05) in the WIR group; the activity of SOD in liver tissues was significantly reduced in the WIR group [(66.6±12.3) U/mgprot vs. (25.1±9.0) U/mgprot, P<0.05]; and the content of MDA in liver tissues was significantly increased in the WIR group [(1.5±0.3) nmol/mgprot vs. (3.6±0.8) nmol/mgprot, P<0.05]; the mRNA expression of Nrf2 and HO-1 were significantly increased (P<0.05) in the WIR group. Compared with the WIR group, ALT and AST level in serum were significantly reduced (P<0.05) in the LC group; the activity of SOD in liver tissues was significantly increased in the LC group [(25.1±9.0) U/mgprot vs. (86.0±11.4) U/mgprot, P<0.05)]; and the content of MDA in liver tissues was significantly reduced in the LC group [(3.6±0.8) nmol/mgprot vs. (1.4±0.2)nmol/mgprot, P<0.05]; the mRNA expression of Nrf2 and HO-1 were significantly increased (P<0.05) in the LC group. Conclusion L-carnitine may attenuate liver WIRI in rats, and this protective effect may be through activating the Nrf2/HO-1 pathway. Key words: L-Carnitine; Liver warm ischemia-reperfusion injury; Nrf2; HO-1; Oxidative stress

Protective effects of petroleum ether extracts of Herpetospermum caudigerum against α-naphthylisothiocyanate-induced acute cholestasis of rats

Ethnopharmacological relevanceThe ripe seeds of Herpetospermum caudigerum have been used in Tibetan folk medicine for treatment of bile or liver diseases including jaundice, hepatitis, intumescences or inflammation. Previously reports suggested that the seed oil and some lignans from H. caudigerum exhibited protective effects against carbon tetrachloride (CCl4)-induced hepatic damage in rats, which may be related to their free radical scavenging effect. However, the protective effect of H. caudigerum against cholestasis is still not revealed. The aim of the present study was to investigate the pharmacological effect and the chemical constituents of the petroleum ether extract (PEE) derived from H. caudigerum against α-naphthylisothiocyanate (ANIT)-induced acute cholestasis in rats. Materials and methodsMale cholestatic Sprague-Dawley (SD) rats induced by ANIT (60mg/kg) were orally administered with PEE (350, 700 and 1400mg/kg). Levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-Glutamyl transpeptidase (γ-GTP), total bilirubin (TBIL), direct bilirubin (DBIL) and total bile acid (TBA), as well as bile flow, and histopathological assay were evaluated. Hepatic malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione S-transferase (GST), and nitric monoxide (NO) in liver were measured to explore the possible protective mechanisms. Phytochemical analysis of PEE was performed by gas chromatography-mass spectrometer (GC-MS). ResultsPEE have exhibited significant and dose-dependent protective effect on ANIT-induced liver injury by reduce the increases in serum levels of ALT, AST, ALP, γ-GTP, TBIL, DBIL and TBA, restore the bile flow in cholestatic rats, and reduce the severity of the pathological tissue damage induced by ANIT. Hepatic MDA, MPO and NO contents in liver tissue were reduced, while SOD and GST activities were elevated in liver tissue. 49 compounds were detected and 39 of them were identified by GC-MS analysis, in which long-chain fatty acids were the main constituents. ConclusionsPEE exhibited a dose-dependently protective effect on ANIT-induced liver injury in cholestatic rats with the potential mechanism of attenuated oxidative stress in the liver tissue, and the possible active compounds were long-chain fatty acids.