Influence of thyroid dysfunction on liver lipid peroxidation and antioxidant status in experimental rats

The purpose of this study was to evaluate the effects of dysthyroidism on lipid peroxidation, antioxidants status, liver, and serum dysfunction parameters in the hypo-/hyperthyroidism-induced rats. Hypothyroidism and hyperthyroidism conditions were induced for 5 weeks by administration of 0.05% benzythiouracile (BTU) and l-thyroxine sodium salt (0.0012%), in drinking water, respectively. The enzymatic activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and the lipid peroxidation product; thiobarbituric acid reacting substances (TBARS) were measured in liver as indicators of oxidative damage. However, liver dysfunction parameters represented by the activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl transferase (GGT), were measured in serum. In hyperthyroidism rats, the TBARS contents of liver have significantly increased compared to those in hypothyroid rats and the controls (p<0.001), associated with a fall of the total antioxidant status (TAS) in the serum of the hyperthyroid rats. The SOD, CAT, and GPx activities in liver of hyperthyroid rats have significantly increased compared to hypothyroid rats and the controls (p<0.001). The AST, ALT, LDH, GGT, and ALP activities increased in the hyperthyroidism rats (p<0.05).We conclude that thyroid dysfunction induces oxidative stress and modifies some biochemical parameters of liver. Our results show the occurrence of a state of oxidizing stress in relation to hyperthyroidism.     

Ozone oxidative preconditioning reduces nitrite levels in blood serum in LPS: induced endotoxic shock in mice

Objective and design  Reactive oxygen species, and also reactive species of nitrogen such as nitric oxide, play an important role in the pathogenesis of peritonitis and septic shock. Ozone oxidative preconditioning (OOP) has shown protective effects in various experimental models of peritonitis in rats and endotoxic shock in mice. Currently, strong evidence is available that this protective effect of OOP is due to its action on the balance between endogenous antioxidants and pro-oxidants, which is favorable for anti-oxidant defense. The aim of this research was to elucidate whether or not OOP is able to reduce nitrite levels in blood serum of mice treated with lipopolysaccharide (LPS). We used an experimental model of endotoxic shock induced by LPS in mice in which the animals were pre-treated with ozone/oxygen mixture for 5 days (once daily), with injection of LPS 24 h thereafter to induce endotoxic shock. Results  Mice pretreated with OOP showed a significant decrease in nitrite levels with all three doses tested [0.2 mg/kg (50.91%), 0.4 mg/kg (47.3%) and 1.2 mg/kg (34.6%)]. Conclusions  Ozone oxidative preconditioning significantly reduced nitrite levels in blood serum of mice with endotoxic shock induced by LPS. We propose that OOP merits further testing in studies as a potential alternative treatment to reduce nitrite levels in patients with sepsis syndrome and septic shock.     

Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin

This experiment pertains to the protective role of naringenin against cadmium (Cd)-induced oxidative stress in the liver of rats. Cadmium is a major environmental pollutant and is known for its wide toxic manifestations. Naringenin is a naturally occurring citrus flavonone which has been reported to have a wide range of pharmacological properties. In the present investigation cadmium (5 mg/kg) was administered orally for 4 weeks to induce hepatotoxicity. Liver damage induced by cadmium was clearly shown by the increased activities of serum hepatic marker enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and serum total bilirubin (TB) along with the increased level of lipid peroxidation indices (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) and protein carbonyl contents in liver. The toxic effect of cadmium was also indicated by significantly decreased levels of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (reduced glutathione (GSH), vitamin C and vitamin E). Administration of naringenin at a dose of (50 mg/kg) significantly reversed the activities of serum hepatic marker enzymes to their near-normal levels when compared to Cd-treated rats. In addition, naringenin significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. The histopathological studies in the liver of rats also showed that naringenin (50 mg/kg) markedly reduced the toxicity of cadmium and preserved the normal histological architecture of the tissue. The present study suggested that naringenin may be beneficial in ameliorating the cadmium-induced oxidative damage in the liver of rats.     

Effect of Zingiber officinale on liver oxidative status and biochemical parameters in rats exposed to paraquat

Oxidative stress caused by reactive oxygen species is one of the major pathogenesis of important diseases of animals and human. Paraquat is widely used as herbicide. The toxicity of paraquat is through induction of oxidative processes in biological systems. Biochemically, this herbicide interferes with intracellular electron transfer system leading to the formation of superoxide anion. Zingiber officinale (ginger) is widely used as a spice and medical treatment for various diseases. The objective of this study was to assess the effect of different levels of ginger extract on antioxidant status and serum metabolites of rats. Sixty male albino Wistar rats were divided in six groups as follows: control (saline); ginger; paraquat; paraquat with 100, 200, and 400 ginger. After 30 days of treatment, the blood was collected by cardiac puncture. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), reduced glutathione (GSH), and lipid peroxidation were estimated. In paraquat-treated group, the serum levels of ALT, AST, and malondialdehyde (MDA) were markedly raised. Administration of ginger extract with paraquat reduced the serum levels of ALT, AST, and MDA. Hepatic SOD, CAT, GPx, GST, and GSH activities were significantly decreased in paraquat-treated group compared to those of control. However, concurrent administration of paraquat with all concentrations of ginger extract had the opposite effect, where it increased the hepatic SOD, CAT, GPx, GST, and GSH activities near to control. The present study demonstrates that administration of ginger extract to rats modulates the antioxidant enzymes and suggests a possible adaptive mechanism to counteract oxidative stress situation.     

Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats

The present study was to evaluate the hepatoprotective effect of hesperetin (HTN) on cadmium (Cd) induced hepatotoxicity in male Wistar rats. Administration of Cd (3 mg/kg body weight/day) subcutaneously for 21 days, the levels of hepatic markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and bilirubin were significantly increased in serum. The levels oxidative stress markers, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), conjugated dienes (CD) and protein carbonyl content (PCC) were also significantly increased while the levels of vitamin C, vitamin E, reduced glutathione (GSH), total sulphydryl group (TSH) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) were significantly decreased in the liver of Cd intoxicated rats. HTN, a flavanone in citrus fruits, administrated orally along with Cd injection for 21 days, significantly revert back the status of serum hepatic markers, oxidative stress markers and antioxidant markers in the liver tissue to near normal level in a dose dependent manner. HTN at a dose of 40 mg/kg body weight/day exhibits significant (p < 0.05) hepatoprotection compared with other two doses (10 and 20 mg/kg body weight/day). The histopathological studies in the liver of rats also supported that HTN (40 mg/kg) markedly reduced the toxicity of Cd and preserved the histoarchitecture of the liver tissue to near normal. Thus, the results suggest that HTN acts as a potent hepatoprotective agent against Cd induced hepatotoxicity in rats.     

The association between immunoexpression levels of oxidant and antioxidant enzymes and lip squamous cell carcinoma

The aim of this study was to investigate the associations among the immunoexpression levels of manganese superoxide dismutase (Mn‐SOD), glutathione peroxidase (GPx), and myeloperoxidase (MPO) in lip squamous cell carcinoma (LSCC) tissues and the clinicopathological characteristics, and prognostic factors in patients with LSCC. The immunoexpression levels of Mn‐SOD, GPx, and MPO were examined in 76 LSCC tissue samples using immunohistochemical staining on tissue microarray slides, and compared to those in normal lip mucosa adjacent to venous lakes (normal controls), normal tissue adjacent to corresponding tumors (NTACT), and recurrent tumors. Associations between immunoexpression levels and clinicopathological characteristics were analyzed using the Student's t‐test. The prognostic factors were analyzed using Cox regression. The immunoexpression levels of Mn‐SOD, GPx, and MPO were significantly different among the normal controls, NTACTs, tumors, and recurrent tumors (Mn‐SOD: p = 0.001, GPx: p < 0.001, MPO: p < 0.001). Lower lip cancer was associated with higher Mn‐SOD immunoexpression levels (p = 0.04) and probably indicated higher oxidative stress. Lymph node involvement with a lower immunoexpression level of MPO (p = 0.007) indicated compensatory mechanism to attenuate oxidative damage. A low Mn‐SOD immunoexpression level was borderline significantly associated with a worse prognosis for disease‐specific survival, and it was probably related to a lower capacity for coping with oxidative stress.     

Evaluation of oxidative stress and antioxidant status: Correlation with the severity of sepsis

Sepsis is a condition caused by infection followed by unregulated inflammatory response which may lead to the organ dysfunction. During such condition, over‐production of oxidants is one of the factors which contribute cellular toxicity and ultimately organ failure and mortality. Antioxidants having free radicals scavenging activity exert protective role in various diseases. This study has been designed to evaluate the levels of oxidative and antioxidative activity in sepsis patients and their correlation with the severity of the sepsis. A total of 100 sepsis patients and 50 healthy controls subjects were enrolled in this study from the period October 2016 to June 2017. The investigation included measurements of oxidative enzyme, myeloperoxidase (MPO ), antioxidant enzymes including superoxide dismutase activity (SOD ) and catalase activity (CAT ) and cytokines (TNF ‐α, IL ‐8 and IFN ‐γ). Furthermore, the level of these activities was correlated with severity of sepsis. Augmented levels of oxidants were found in sepsis as demonstrated by DMPO nitrone adduct formation and plasma MPO level activity (1.37 ± 0.51 in sepsis vs 0.405 ± 0.16 in control subjects). Cytokines were also found to be increased in sepsis patients. However, plasma SOD and CAT activities were significantly attenuated (P  < .001) in the sepsis patients compared with controls subjects. Moreover, inverse relation between antioxidant enzymes (SOD and CAT ) and organ failure assessment (SOFA ), physiological score (APACHE II ), organ toxicity specific markers have been observed as demonstrated by Pearson's correlation coefficient. This study suggests that imbalance between oxidant and antioxidant plays key role in the severity of sepsis.     

Antagonism of α2A-adrenoceptor: a novel approach to inhibit inflammatory responses in sepsis

Sepsis is a systemic inflammatory response syndrome (SIRS) when an infection is the etiology of SIRS. Our previous studies have indicated that the release of the sympathetic neurotransmitter, norepinephrine (NE), from the gut is increased in sepsis, and that NE potentiates endotoxin-induced tumor necrosis factor (TNF)-α upregulation via the A subtype of α₂-adrenoceptors (i.e., α_2A-AR) expressed on the surface of Kupffer cells. A specific antagonist for α_2A-AR, 2-[(4,5-dihydro-1H-imidazol-2-yl) methyl]-2,3-dihydro-1-methyl-1H-isoindole maleate (BRL-44408 maleate), reduces TNF-α secretion in cultured Kupffer cells. We, therefore, hypothesize that administration of BRL-44408 maleate inhibits inflammatory responses and reduces organ injury in sepsis. To study this, sepsis was induced in male rats by cecal ligation and puncture (CLP). At 5 h after CLP, BRL-44408 maleate (0.3125, 0.625, 1.25, 2.5, or 5.0 mg/kg BW) or vehicle (1-ml normal saline) were administered intravenously over a period of 30 min. Blood and intestinal samples were collected at 20 h after CLP. Serum levels of TNF-α, interleukin (IL)-6, IL-10, keratinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2), liver enzymes (i.e., aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), and lactate were measured. The intestinal levels of TNF-α, IL-6, and myeloperoxidase (MPO) activities were also analyzed. In additional groups of animals, the necrotic cecum was excised at 20 h post-CLP, and the 10-day survival was recorded. Our results showed that serum levels of proinflammatory cytokines (TNF-α and IL-6), anti-inflammatory cytokine (IL-10), chemokines (KC, MIP-2), liver enzymes (AST and ALT), lactate, and intestinal levels of TNF-α, IL-6, and MPO were significantly elevated at 20 h after CLP. Administration of BRL-44408 maleate significantly reduced serum levels of proinflammatory cytokines, chemokines, liver enzymes, and lactate, and dramatically decreased TNF-α, IL-6, and MPO levels in the gut. However, it has no statistical effects on the elevated serum levels of IL-10. Moreover, BRL-44408 maleate at the doses of 2.5 or 5.0 mg/kg BW significantly increased the survival rate after CLP and cecal excision. In conclusion, modulation of the sympathetic nervous system by blocking α_2A-AR appears to be a novel treatment for inflammatory conditions such as sepsis.     

Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin-induced experimental hepatoxicity in rodents

The present study is aimed at investigating the effect of curcumin (CMN) in salvaging endotoxin-induced hepatic dysfunction and oxidative stress in the liver of rodents. Hepatotoxicity was induced by administering lipopolysaccharide (LPS) in a single dose of 1 mg/kg intraperitoneally to the animals, which were being treated with CMN daily for 7 days. Liver enzymes serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP), total bilirubin and total protein were estimated in serum. Oxidative stress in liver tissue homogenates was estimated by measuring thiobarbituric acid reactive substances (TBARS), glutathione (GSH) content and superoxide dismutase (SOD) activity. Serum and tissue nitrite was estimated using Greiss reagent and served as an indicator of NO production. A separate set of experiments was performed to estimate the effect of CMN on cytokine levels in mouse serum after LPS challenge. LPS induced a marked hepatic dysfunction evident by rise in serum levels of ALT, AST, ALP and total bilirubin (P < 0.05). TBARS levels were significantly increased, whereas GSH and SOD levels decreased in the liver homogenates of LPS-challenged rats. CMN administration attenuated these effects of LPS successfully. Further CMN treatment also regressed various structural changes induced by LPS in the livers of rats and decreased the levels of tumour necrosis factor-alpha and interleukin-6 in mouse plasma. In conclusion, these findings suggest that CMN attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of NO, oxygen free radicals and cytokines.     

Ameliorating effect of phytoestrogens on CCl4-induced oxidative stress in the livers of male Wistar rats

Glutathione-S-transferases and glutathione play a key role in the detoxification of most toxic agents. In the present study, the protective effects, if any, of isoflavone phytoestrogens--genistein and daidzein on the carbon tetrachloride (CCl4) induced changes in the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione S transferase (GSH) and levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS)-were studied. The activities of ALT and AST were assayed in the serum, whereas the activity of GST and levels of GSH and TBARS were determined in the livers of rats. The current study involved the division of animals into two main groups: (i) rats pretreated with genistein and daidzein for three days; and (ii) non-pretreated rats. In the pretreated group, rats received oral doses of genistein (7.9 micromol/kg body weight) and daidzein (7.9 micromol/kg body weight) for three consecutive days (once daily) followed by oral dose of CCl4 on the 4th and the 5th day concurrently with the phytoestrogens-genistein or daidzein. In the non-pretreated group animals received oral dose of CCl4 (1 ml/kg body weight) for two consecutive days along with the phytoestrogens-genistein or daidzein. Treatment of male rats with CCl4 significantly elevated the activity of ALT and AST in serum and levels of TBARS in the liver. On the other hand, CCl4 resulted in decreased activity of GST and lowered the GSH levels. Coadministration of genistein and daidzein with CCl4 could not restore the alterations in the activity of ALT and AST caused by CCl4 to normal control levels. However, repeated dose treatments with genistein and daidzein for three days prior to the administration of CCl4 restored such alterations to normal levels. Our results indicate that genistein is more effective than daidzein in counteracting the inhibition of GST activity caused by CCl4 and restoring it to normal levels. Genistein was also more effective than daidzein restoring the induced TBARS levels caused by CCl4 to normal control levels when rats were pretreated with the isoflavone orally for three days. It has been observed that the tested isoflavonoids were able to antagonize the toxic effects of CCl4. Such counteracting effects were more pronounced for genistein and when the phytoestrogens were administered as repeated doses prior CCl4 administration.     

Effects of tocotrienol-rich fraction on exercise endurance capacity and oxidative stress in forced swimming rats

The present study aimed to examine the effects of tocotrienol-rich fraction (TRF) on exercise endurance and oxidative stress in forced swimming rats. Rats fed on isocaloric diet were orally given 25 (TRF-25) and 50 (TRF-50) mg/kg of TRF, or 25 mg/kg d-α-tocopherol (T-25) whilst the control group received only the vehicle for 28 days, followed by being forced to undergo swimming endurance tests, with measurements taken of various biochemical parameters, including blood glucose, lactate and urea nitrogen, glycogen, total antioxidant capacity, antioxidant enzymes, thiobarbituric acid-reactive substances (TBARS), and protein carbonyl. Results showed that the TRF-treated animals (268.0 ± 24.1 min for TRF-25 and 332.5 ± 24.3 min for TRF-50) swam significantly longer than the control (135.5 ± 32.9 min) and T-25-treated (154.1 ± 36.4 min) animals, whereas there was no difference in the performance between the T-25 and control groups. The TRF-treated rats also showed significantly higher concentrations of liver glycogen, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as of muscle glycogen and SOD than the control and the T-25-treated animals, but lower levels in blood lactate, plasma and liver TBARS, and liver and muscle protein carbonyl. Taken together, these results suggest that TRF is able to improve the physiological condition and reduce the exercise-induced oxidative stress in forced swimming rats.     

Acetaminophen-induced liver damage in mice: Effects of some medicinal plants on the oxidative defense system

Paracetamol (acetaminophen, PCM) is widely used as an over-the-counter analgesic and antipyretic drug. Intake of a large dose of PCM may result in severe hepatic necrosis. Oxidative stress mediated by oxidative capacities of the PCM metabolite (N-acetyl-p-benzoquinoneimine (NAPQI), is considered as the main cause of hepatotoxicity of PCM. This work therefore seeks to induce liver damage in mice using single dose (25 0mg/kg) of acetaminophen and to evaluate the possible protective effects of administration (100mg/kg) of some medicinal plants (Kigelia africana, Calotropis procera, Hibiscus sabdariffa and Alchornea cordifolia) on PCM-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. Equally, comparative effects of these plants on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), gluthathione peroxidase (GPx), and delta-aminolevulinate dehydratase (delta-ALA-D) activities, were also evaluated in the mouse liver homogenate. Paracetamol caused liver damage as evident by statistically significant (P<0.05) increased in plasma activities of AST and ALT. There were general statistically significant losses in the activities of SOD, GPx, CAT, and delta-ALA-D and an increase in TBARS in the liver of paracetamol-treated group compared with the control group. However, all the tested plants except Calotropis procera were able to counteract these effects. The present results suggest that these plants can act as hepatoprotectives against paracetamol toxicity and that the mechanism by which they do this is by acting as antioxidants.     

Erythrocytes oxidative damage and hematological effects of 2,4,4′,5-tetrachlorodiphenyl sulfone in rats

The effects of subchronic exposure to tetrachlorodiphenyl sulfone (TCDS) on hematological parameters [white blood cells (WBC), red blood cells (RBC), mean cell volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hemoglobin (Hb) and hematocrite (Ht) levels] were examined. Oxidative stress in erythrocytes was also assessed by measuring thiobarbituric acid reactive substances (TBARS) and enzyme antioxidant activities [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)]. TCDS was administered orally, dissolved in water, ad libitum to 12 female rats at 28.9 mg/kg/day for 6 or 12 weeks. Results showed that TCDS induced significant decreases in RBC, Hb, and Ht. Whereas MCV, MCH, and MCHC remain unchanged and WBC increased only in the second period of the study. Moreover erythrocyte TBARS level increased, and antioxidant enzyme (SOD, GPx, and CAT) activities decreased. We concluded that TCDS intoxication promotes erythrocyte oxidative damage and disrupt hematological constituents in rats.     

Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats

The present study was undertaken to evaluate the protective effect of selenium against arsenic-induced oxidative damage in experimental rats. Males were randomly divided into four groups where the first was served as a control, whereas the remaining groups were respectively treated with sodium selenite (3 mg/kg b.w.), sodium arsenite (5.55 mg/kg b.w.) and a combination of sodium arsenite and sodium selenite. Changes in liver enzyme activities, thiobarbituric acid reactive substances (TBARS) level, antioxidants and reduced glutathione (GSH) contents were determined after 3 weeks experimental period.Exposure of rats to As caused a significant increase in liver TBARS compared to control, but the co-administration of Se was effective in reducing its level. The activities of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) of As-treated group were found lower compared to the control and the Se-treated group. The co-administration of Se had an additive protective effect on liver enzyme activities compared to As-treated animals. On the other hand, a significant increase in plasmatic activities of AST, ALT and ALP was observed in As-treated group. The latter was also exhibited a decrease in body weight and an increase in liver weight compared to the control. The co-administration of Se has decreased the activities of AST, AST and ALP and improved the antioxidant status as well. Liver histological studies have confirmed the changes observed in biochemical parameters and proved the beneficial role of Se. To conclude, results suggest that As exposure enhanced an oxidative stress by disturbing the tissue antioxidant defense system, but the Se co-administration protected liver tissues against As intoxication probably owing to its antioxidant properties.     

Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver

Endotoxemia-induced hepatotoxicity is characterized by disturbed intracellular redox balance, excessive reactive oxygen species (ROS) generation inducing DNA, proteins and membrane lipid damages. In the present study, the protective effects of montelukast (MNT) against Escherichia coli lipopolysaccharides (LPS)-induced oxidative stress were investigated in rat liver. LPS (10 mg/kg, i.p.) was injected and the animals were sacrificed 6 h after LPS challenge. MNT (10 mg/kg) was administered orally for seven successive days before endotoxemia induction. Blood samples were withdrawn for assessing the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and levels of serum total bilirubin, total protein, tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). Livers were dissected out and used for histological examination or stored for the determination of malondialdehyde (MDA), protein carbonyl content (PCC), reduced glutathione (GSH) levels, enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO). Sepsis significantly increased ALT, AST, ALP, LDH, total bilirubin, TNF-α and IL-1β, MPO, MDA and PCC levels and decreased total protein, GSH and enzymatic antioxidants (CAT, SOD and GSH-Px). MNT decreased the markers of liver injury (AST, ALT, ALP, LDH, and total bilirubin), inflammatory biomarkers (TNF-alpha, IL-1β), MDA, PCC and MPO after LPS challenge. In conclusion, MNT abrogates LPS-induced markers of liver injury and suppresses the release of inflammatory and oxidative stress markers via its antioxidant properties and enhancement enzymatic antioxidant activities.     

Hemostasis for Severe Hemorrhage with Photocrosslinkable Chitosan Hydrogel and Calcium Alginate

In patients with severe hemorrhage, complications such as shock or death may occur if the patient is not treated appropriately and expeditiously. To create a hemostat kit for severe hemorrhage, ultraviolet light irradiation was applied to photocrosslinkable chitosan hydrogel and calcium alginate. As a hemorrhage model, the femoral arteries and veins of anesthetized rats were cut. Hemodynamics and hematological parameters including red blood cell (RBC) count, hemoglobin concentration, hematocrit, white blood cell (WBC) count, and platelet count, and serum parameters including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured as a marker of hemostasis. In rats for which no procedure was used, death occurred within 30 min. By using the hydrogel hemostat, the survival rate rose to 75% or more. RBC count, hemoglobin, hematocrit, and platelet levels were not significantly changed for 3 days. WBC count increased 1 day after hemostasis. AST and ALT increased 1 day after hemostasis, but it decreased 3 days later. The photocrosslinkable chitosan hydrogel and calcium alginate were biodegraded at 3 and 28 days, respectively, by neutrophils and keratinocyte chemoattractant.     

Studies on preventive effects of diphenyl diselenide on acetaminophen-induced hepatotoxicity in rats

Organoselenium are compounds with important antioxidant activity and with many biological activities interesting from pharmacological point of view. The aim of this study was to evaluate the protective effect of diphenyl diselenide (PhSe)₂ on hepatotoxicity caused by administration of acetaminophen (AA) in rats. Rats received (PhSe)₂ orally (31 mg/kg, dissolved in canola oil) for 2 days. After the second day of treatment, rats received AA orally (2 g/kg) in unique dose. Twenty-four hours after the last administration of AA, plasma was used for biochemical assays aspartate (AST) and alanine aminotransferases (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), γ-glutamyl transferase (γ-GT) activities. Glutathione-S-transferase (GST), δ-aminolevulinic dehydratase (δ-ALA-D) and catalase activities as well as ascorbic acid and TBARS levels were determined in the liver of rats. (PhSe)₂ protected against the increase in AST, ALT, ALP, LDH and γ-GT activities induced by AA exposure to rats. The histological data showed that sections of liver from AA-exposed rats presented intense cellular necrosis, characterized by the presence of Kupffer cells and other infiltrating cells, mainly around of the centrilobular vein. (PhSe)₂ significantly attenuated AA-induced hepatic histopathological alterations. Administration of (PhSe)₂ protected against the increase in TBARS levels and the decrease in δ-ALA-D and GST activities as well as ascorbic acid content induced by AA exposure in rats. Catalase activity remained unaltered in all treated groups. The protective effect of (PhSe)₂ against hepatotoxicity caused by AA exposure in rats was demonstrated.     

Cobalt chloride induces hepatotoxicity in adult rats and their suckling pups

To assess liver damages in pregnant and lactating rats and in their suckling pups, wistar female rats were given through drinking water 350 ppm of CoCl₂ (157 ppm Co²⁺) from the 14th day of pregnancy until day 14 after delivery. The effects of cobalt chloride on lipid peroxidation levels, antioxidant enzyme activities, lipid profile and histopathology aspects of liver were evaluated. Biochemical results showed that lipid peroxidation increased significantly in Co-treated rats, as evidenced by high liver thiobarbituric acid-reactive substance (TBARS) levels. Alteration of the antioxidant system in treated group was confirmed by the significant decline of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and reduced glutathione (GSH) content in liver of suckling pups and their mothers. Moreover, CoCl₂ exposure induced an increase in the activities of the aspartate transaminase (AST), alanine transaminase (ALT), lactate deshydrogenase (LDH) and bilirubin levels in pups and their mothers while liver LDH activity and plasma albumin level were significantly decreased. On the other hand, cobalt chloride induced a marked hypoglycemia, a significant decline in triglycerides and total cholesterol levels. Histological studies showed an infiltration of mononuclear cells and vascular congestion in liver of pups and their mothers.Based on the present findings, exposure of rats to CoCl₂ during late pregnancy and early postnatal period affects antioxidant enzyme activities and lipid peroxidation indicating liver damage in mothers and their offspring.     

Protective effects of aqueous extract of Artemisia campestris against puffer fish Lagocephalus lagocephalus extract-induced oxidative damage in rats

The aerial parts of Artemisia campestris are often used in Tunisian poisoning cases and are known to possess significant antioxidant activities. The objective of this study is to evaluate the protective effects of an aqueous extract (5 g/l) of A. campestris leaves and stems (AE), on oxidative damages induced by liver extract (LT) from poisonous fish Lagocephalus lagocephalus in wistar rats. AE was found to contain large amounts of K⁺, Na⁺, Ca⁺⁺ and significant antioxidant capacities highlighted by high level of polyphenols and scavenging activities for DPPH and superoxide anion.LT-injected rats (1 ml/100 g body wt) for 10 days showed (1) a reduced appetite and diarrhea resulting in a lower growth rate than controls, (2) a decrease in serum ALT and AST activities suggesting liver functional disorders, (3) an increase of serum urea and creatinine and reduced serum sodium and potassium concentrations highlighting renal insufficiency and (4) an oxidative stress as evidenced by the raise of TBARS and the inhibition of SOD, CAT and GSH-Px activities in liver, kidney and brain tissuesAbsorption of AE as a drink, for 20 days (10 pre-treatment days+10 experiment days) did not lead significant change of studied parameters but prevented all the disorders induced by LT.     

脓毒症后leptin对肠道功能的影响及对肝肾功能的保护作用

目的： 研究脓毒症对肝、肾功能及肠道相关酶活性的影响，探讨瘦素（leptin）在急性炎症反应中的作用。方法： 建立小鼠盲肠结扎致脓毒症模型，采用96孔分光光度法检测血清丙氨酸氨基转移酶（ALT）、尿酸（UA）和肠组织匀浆液中髓过氧化物酶（MPO）、谷胱甘肽-S转移酶（GST）、黄嘌呤氧化酶（XOD）、超氧化物歧化酶（SOD）等，同时以HE染色方法观察肠道组织病理学改变。结果： 脓毒症后6 h，血清UA水平［（521.92±91.86） μmol/L］明显高于假手术组［（330.12±94.15） μmol/L］，而12 h ALT［（83.55±40.44） U/L］和UA［（474.03±75.22）　μmol/L］均高于假手术组［（66.23±16.80） U/L］和［（320.95±99.14） μmol/L］。采用腹腔内注射leptin（0.1 mg/kg）和吲哚美辛（2 mg/kg），12 h时ALT和UA水平均明显低于脓毒症组（P<0.05）。此外，伴有肠道组织MPO、GST、XOD和SOD活性的改变。结论： 在脓毒症过程中，微量leptin体外注射可以发挥改善和稳定肝肾功能的明显作用，其机制可能同其影响肠道多种与自由基、巯基和嘌呤代谢相关酶的功能有关，而且吲哚美辛在一定程度上有类似的效应，但所用剂量明显高于leptin水平。