Hypericum perforatum protects against hepatic injury induced by carbon tetrachloride

Extracts of Hypericum perforatum (St. John’s wort) have gained much interest for their antidepressant effects. The aim of the present study was to investigate the effect H. perforatum on the development of liver injury induced by treatment with carbon tetrachloride (CCl₄) in rats. Liver damage was induced by administration of carbon tetrachloride (2.8?ml/kg in olive oil). H. perforatum (25, 50, and 100?mg/kg) alone or combined with silymarin (25?mg/kg) was given once daily orally simultaneously with CCl₄ and for 14?days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. In CCl₄-treated rats given H. perforatum at 25?mg/kg per day for 2?weeks, the elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum were significantly less than in the CCl₄ control group. Serum ALT level decreased by 14.4% and AST level by 16.6% of their corresponding control value, respectively. Serum alkaline phosphatase (ALP) level was not significantly reduced by H. perforatum at 25?mg/kg. The addition of silymarin at the dose of 25?mg/kg to H. perforatum resulted in further decrease in liver enzymes compared with H. perforatum treatment alone. Serum ALT decreased by 40.2%, AST by 37.9%, and ALP by 38.1% of the control value, respectively, after combining H. perforatum at 25?mg/kg and silymarin. On the other hand, treatment with H. perforatum at 50 or 100?mg/kg reduced serum ALT levels by 37.9–52.6%, AST levels by 30.2–53.2%, and ALP by 48.5–51.5%, respectively. Silymarin given in combination with the above doses of H. perforatum reduced serum ALT by 58.7–63.3%, AST by 56.6–60.9%, and ALP levels by 54.7–58.8%, respectively. Meanwhile, silymarin alone decreased serum ALT by 56.8%, AST by 62.6%, and ALP levels by 55.1%, respectively. The administration of CCl₄ resulted in marked increase in nitric oxide level in serum (the concentrations of nitrite/nitrate) as compared to the normal group. Treatment with H. perforatum resulted in a dose-dependent decrease in serum nitric oxide level compared with the CCl₄ control group. Blood levels of reduced glutathione were markedly decreased in CCl₄-treated rats. Reduced glutathione levels were increased significantly by 100?mg/kg H. perforatum and restored to near normal values by silymarin treatment. Histopathological examination also indicated that CCl₄-induced liver injury was less severe in the H. perforatum-treated groups. Taken together, the present results show that H. perforatum reduces the extent of hepatic injury caused by CCl₄ in rats and this effect is increased by co-administration of silymarin. This suggests the beneficial effect of silymarin administration to depressed patients with liver disease treated with H. perforatum.     

Protective effect of kombucha tea against acetaminophen-induced hepatotoxicity in mice: a biochemical and histopathological study

Acetaminophen overdose causes severe hepatotoxicity leading to liver failure in experimental animals and humans. This study was undertaken to evaluate the protective effect of kombucha tea (KT) against acetaminophen-induced hepatotoxicity. Forty male Balb/c mice were divided into four equal groups: (1) the control group, (2) KT-treated group, (3) acetaminophen-treated group, and (4) KT/acetaminophen-treated group. All mice in group 4 were given KT orally for 7?days before a single hepatotoxic dose of acetaminophen (1,000?mg/kg orally). Activities of liver marker enzymes in serum; aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP); and total protein (TP), albumin (ALB), and direct and total bilirubin levels were determined. Acetaminophen challenge caused significant increases in the levels of bilirubin and liver enzymes (AST, ALT, ALP, and LDH), while TP and ALB levels were reduced significantly. Histopathologic assessments showed that severe glycogen storage in hepatocytes, hepatocellular degeneration and necrosis, mononuclear cell infiltration in portal area, dilation of central veins, and capillarization also reduced in KT/acetaminophen group compared to acetaminophen-treated mice. In conclusion, these findings suggest that KT has protective effect on acetaminophen-induced hepatotoxicity.     

Effect of Crataegus extract on carbon tetrachloride-induced hepatic damage

The current study evaluated the effect of a standardized Crataegus extract on liver injury induced by acute carbon tetrachloride (CCl₄) administration in rats. Crataegus extract (10, 20 or 40?mg/kg), silymarin (25?mg/kg) or saline (control) was given once daily orally simultaneously with CCl₄ and for 1?week thereafter. Crataegus extract given at the above doses reduced serum alanine aminotransferase (ALT) levels by 28.8, 31.8 and 36.4%, respectively, when compared to the CCl₄ control group. Serum aspartate aminotransferase (AST) levels decreased by 14.3, 15.5 and 20.6%, respectively, while alkaline phosphatase (ALP) decreased by 21.8% by the extract at 40?mg/kg. The administration of silymarin reduced ALT, AST and ALP levels by 66.8, 64.9 and 60%, respectively. In CCl₄-treated rats, the increase in serum nitric oxide (nitrite/nitrate) level, the histological liver damage as well as the decrease in mucopolysaccharide and protein content of hepatocytes were all improved by Crataegus extract at 40?mg/kg and almost normalized by silymarin. These results suggest that treatment with Crataegus extract improves the CCl₄-induced hepatic injury in rats.     

Effect of Echinacea alone or in combination with silymarin in the carbon-tetrachloride model of hepatotoxicity

Echinacea preparations are widely used in the prevention or treatment of upper respiratory tract infections. The present study aimed to investigate the effect of a standardized Echinacea extract in experimentally induced liver toxicity and whether this herb would have a modulating effect on the silymarin-induced hepatoprotection in rats. Liver damage was induced by the administration of carbon tetrachloride (CCl₄). Echinacea extract (18 or 36?mg/kg) alone or combined with silymarin (25?mg/kg), silymarin only (25?mg/kg), or saline (control) was given once daily orally simultaneously with CCl₄ and for 1?week thereafter. Serum alanine aminotransferase (ALT) or aspartate aminotransferase were not significantly changed by treatment with Echinacea, but alkaline phosphatase (ALP) in serum decreased by 23.6% by the extract at 36?mg/kg. Silymarin given in combination with either dose of Echinacea resulted in 34.9% and 57.8% reduction in AST, 42.7% and 58% reduction in ALT and 41% and 60% reduction in ALP, compared with CCl₄ control group. Silymarin alone reduced ALT, AST, and ALP levels by 58.8%, 61.2%, and 62.2%, respectively. Histopathological examination revealed a mild decrease in degenerated hepatocytes after treatment with 36?mg/kg of Echinacea. Noticeable improvement in the liver damage was observed upon the addition of silymarin to Echinacea. A marked decrease of intracellular protein and glycogen staining was evident after the administration of CCl₄. Slight improvement in protein and glycogen staining was noted after 36?mg/kg of Echinacea. Increased hepatic protein and glycogen staining intensity was observed after silymarin and Echinacea co-treatment compared with Echinacea-only treated groups. Silymarin only treatment resulted in more or less normal histopathological and histochemical findings. The present results suggest that administration of Echinacea extract reduces the hepatoprotective effect of silymarin. Such finding is likely to have important clinical significance in patients with hepatic disease on silymarin treatment.     

The dopamine agonist piribedil exerts hepatoprotective effects on carbon tetrachloride-induced hepatic damage

This study aimed to investigate the effect of piribedil, a drug used for the treatment of Parkinson’s disease and which has direct dopaminergic stimulating action, on the acute hepatic injury in mice. Hepatotoxicity was induced by CCl₄ orally (0.28 ml/kg). Piribedil at three dose levels (4.5, 9, or 18 mg/kg) or silymarin (25 mg/kg) was given orally daily for 7 days, starting at time of administration of CCl₄. Liver damage was assessed by determining liver serum enzyme activities and by hepatic histopathology. Piribedil administration lessened the increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) and also prevented the development of hepatic necrosis caused by CCl₄. The effect of piribedil was dose-dependent one. Piribedil administered at the above doses caused significant reduction in the elevated plasma ALT by ?36.3%, ?42.8%, and ?52.4% and ALP by ?25%, ?36.9%, and ?57.1%, respectively. AST decreased by ?36.4% and ?46.2% by piribedil at 9 or 18 mg/kg, respectively. In comparison, the elevated serum ALT, AST, and ALP levels decreased to ?69.6%, ?64.2%, and ?68.5% of control values, respectively, by silymarin. Histopathologic examination of the livers of CCl₄-treated mice administered piribedil at 9 mg/kg showed noticeable amelioration of the liver tissue damage, while piribedil at 18 mg/kg resulted in restoration of the normal architecture of the liver tissue as well as noticeable increase in the protein content of hepatocytes. It is concluded that administration of the dopaminergic agonist piribedil in a model of liver injury induced by CCl₄ results in amelioration of liver damage.     

Evaluation of the Antioxidant Effects of Ziziphus Mauritiana Lam. Leaf Extracts Against Chronic Ethanol-Induced Hepatotoxicity in Rat Liver

Chronic alcohol ingestion is known to increase the generation of reactive oxygen species (ROS), thereby leading to liver damage. Antioxidant enzymes act individually or in combination to reduce or counter the effect of these ROS. Chronic administration of alcohol at (40% v/v, 1ml/100g), for 6 weeks showed a significant (p<0.05) elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). There was also a significant (p<0.05) decreased levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase compared to control rats. Pre-treatment of rats with 200, 400 mg/kg body weight of aqueous leaf extract of Ziziphus mauritiana or 100 mg/kg silymarin resulted in a significant (p<0.05) decreased levels of ALT, AST, ALP, and TB with levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase showing a significant (p<0.05) increase compared to group administered alcohol only. Histopathology of rat liver administered with alcohol only resulted in severe necrosis, mononuclear cell aggregation and fatty degeneration in the central and mid zonal areas which was a characteristic of a damaged liver. Pre-treatment with the aqueous extract of Ziziphus mauritiana or silymarin reduced the morphological changes that are associated with chronic alcohol administration. The presence of tannins, saponins and phenolic compounds observed in the plant extract could be responsible for the observed effects of decreasing the levels of injured tissue marker and lipid peroxidation.     

Plasma chemistry reference values in the gyr falcon (Falco rusticolus)

Blood samples were collected from 102 clinically healthy gyr falcons (Falco rusticolus) over a time period of approximately 3 years as part of routine examination procedures. Standard blood chemistry analyses were carried out to establish normal reference values for the species. Plasma chemistry analyses included alkaline phosphatase (ALP), amylase, blood urea nitrogen, bile acids, calcium, cholesterol, creatinine, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), glucose, phosphate, iron, total protein, total bilirubin, and uric acid. Reference intervals were determined using a quantile approach with 90 % confidence intervals of the limits. Juveniles and adults differ in ALT, creatinine, AST, glucose, LDH, and uric acid. Sexes differ in ALP, CK, AST, and phosphorus. This study provides valuable information on the plasma biochemistry values for gyr falcons that may help in the medical management of this endangered and commonly used falconry species.     

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.     

Micronised purified flavonoid fraction alleviates the carbon tetrachloride-induced hepatic injury

Micronised purified flavonoid fraction is a phlebotonic drug that is widely used in lower limb oedema due to chronic venous or lymphatic insufficiency. The aim of this study is to evaluate the effects of micronised purified flavonoid fraction (Daflon®) on hepatic injury caused by the administration of carbon tetrachloride (CCl₄) in rats. Micronised purified flavonoid fraction (MPFF: 2.25, 4.5 or 9 mg/kg), silymarin (25 mg/kg) or MPFF (2.25, 4.5 or 9 mg/kg) combined with silymarin was given once daily orally simultaneously with CCl₄ and for 1 week thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology and morphometry as well as by measuring the optical density of total alkaline phosphatase enzyme activity. Micronised purified flavonoid fraction given at the above doses conferred significant protection against the hepatotoxic actions of CCl₄ in rats, reducing serum alanine aminotransferase (ALT) levels by 25.7, 43.1, and 75.6 %, respectively, compared to CCl₄ control group. Serum aspartate aminotransferase (AST) levels decreased by 16.8, 35.6 and 62.9 %, respectively. Alkaline phosphatase (ALP) decreased by 17.9, 21 and 64.7 % by MPFF at 2.25, 4.5 and 9 mg/kg, respectively. In rats treated with MPFF–silymarin combination, ALT decreased by 27.5, 51.6, and 74.1 %, AST decreased by 38.4, 45.6, and 74.5 %, while ALP deceased by 44.3, 60.0, and 74.4 %. On the other hand, the administration of silymarin alone reduced ALT, AST and ALP levels by 78.9, 80.4 and 62.7 %, respectively. Histopathological studies also indicated that MPFF decreased the area of damage and improved hepatic architecture in CCl₄-treated rats. In addition, MPFF markedly improved the optical density of total alkaline phosphatase enzyme activity. These results suggest that treatment with MPFF protects against CCl₄-induced hepatic injury in rats and might find utility in treating chronic liver disease in man.     

Effects of lead acetate exposure on metabolic enzyme activities in selected tissues of common carp (Cyprinus carpio)

The aim of the current study was to determine the effects of lead exposure on tissue enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in liver, kidney, brain, and gill of common carp. Lead acetate exposure (7.0 mg L^?1, 10 days) caused a significant elevation of AST in the liver as compared to control group (P?<?0.05). The activity of ALT was increased significantly in the liver, kidney, and brain homogenates following lead acetate exposure. Treatment with lead acetate caused significant increase in ALP values in the kidney and gill as compared to control group. Moreover, LDH activity was increased following lead acetate exposure in all examined tissues, although the increase was only significant in the liver. The results suggested that lead acetate exposure in common carp leads to interactions between this metal and biological systems, which could affect metabolic enzyme activities in some tissues. However, much more extensive biochemical and toxicological research are needed for better understanding of the molecular basis of lead-induced tissue enzyme alterations.     

Study of the effect of Cannabis sativa on liver and brain damage caused by thioacetamide

Cannabis sativa preparations are the most widely used illicit drugs worldwide. The present study aimed to examine the effect of C. sativa extract on liver injury caused by thioacetamide in the rat. Thioacetamide was administered at 50 mg/kg twice weekly via subcutaneous route (s.c.) for 2 weeks. Starting from the first dose of thioacetamide, rats were treated with either C. sativa at doses of 10 or 20 mg/kg (expressed as Δ⁹-tetrahydrocannabinol), silymarin (25 mg/kg) or saline, once daily s.c., for 2 weeks. Reduced glutathione (GSH), lipid peroxidation (malondialdehyde; MDA) and nitric oxide concentrations were measured in the liver and brain. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), paraoxonase 1 activities (PON1) and total proteins were determined in serum. Hepatic injury was also determined via histological examination of liver sections. The administration of only cannabis to saline-treated rats had no significant effect on serum liver enzymes or on the hepatic levels of GSH, MDA or nitric oxide. Serum PON1 decreased by 21.9 % by 20 mg/kg cannabis. The level of MDA and nitric oxide in brain decreased by only cannabis administration. In thioacetamide-treated rats, the administration of cannabis extract (10 or 20 mg/kg) did not alter the level of MDA, GSH or nitric oxide in hepatic tissue. Serum ALT or AST were not significantly altered, but ALP increased significantly by 38.9 % after treatment with 20 mg/kg cannabis. Serum PON1 activity which showed marked decrease in thioacetamide-treated rats, increased by 18.9 and 151 % after C. sativa treatment. Serum proteins increased after the administration of cannabis (by 20.4 and 21.3 %, respectively). In brain tissue, both MDA and nitric oxide were significantly decreased by cannabis. Meanwhile, treatment with silymarin resulted in significant decrease in MDA and increased GSH in the liver tissue. Serum AST, ALT and ALP were significantly decreased, while PON1 activity was increased after silymarin. In brain, MDA decreased by 27.9 % after silymarin. Cannabis alone caused histological liver damage and fibrosis and neuronal degeneration. The liver tissue damage and brain degeneration caused by thioacetamide were enhanced by cannabis but almost prevented by silymarin treatment. It is concluded that the administration of C. sativa exacerbates the thioacetamide-induced liver and brain injury.     

Hepatoprotective effects of Cynara extract and silymarin on carbon tetrachloride-induced hepatic damage in rats

The aim of this study was to investigate the effect of Cynara scolymus extract alone or in combination with silymarin on the carbon tetrachloride (CCl₄)-induced hepatic injury in rats. Cynara extract (30, 60, or 120 mg/kg), silymarin (25 mg/kg), or Cynara extract (30, 60, or 120 mg/kg) combined with silymarin was given once daily orally simultaneously with CCl₄ and for 2 weeks thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Cynara extract given at the above doses conferred significant protection against the hepatotoxic actions of CCl₄ in rats, reducing serum alanine aminotransferase (ALT) levels by 21 %, 24.3 %, and 35.8 %, respectively, compared to CCl₄ control group. Serum aspartate aminotransferase (AST) levels decreased by 15.5 %, 39.6 %, and 44.3 %, respectively. Alkaline phosphatase (ALP) decreased by 21 % and 25 % by Cynara extract at 60 and 120 mg/kg, respectively. In rats treated with silymarin combined with Cynara extract (30, 60, or 120 mg/kg), ALT decreased by 32.6 %, 34.5 %, and 51.6 %, and AST decreased by 20 %, 50.6 %, and 58.3 %, respectively. Meanwhile, ALP decreased by 22.4 % and 29.7 % after treatment with silymarin combined with Cynara extract (60 or 120 mg/kg). On the other hand, the administration of silymarin alone reduced ALT, AST, and ALP levels by 55.3 %, 67.1 %, and 52.5 %, respectively. The administration of CCl₄ resulted in marked increase in nitric oxide level in serum (the concentrations of nitrite/nitrate) as well as marked decrease in blood levels of reduced glutathione (GSH). Treatment with Cynara extract resulted in a dose-dependent decrease in serum nitric oxide level and increased GSH in blood compared with CCl₄ control group. Silymarin showed an additive effect resulting in further decrease in serum nitric oxide. Silymarin only treatment caused a marked reduction in serum nitric oxide level and increased GSH in blood. Histopathological studies also indicated that CCl₄-induced liver injury was less severe in Cynara extract-treated groups. Metabolic perturbations caused by CCl₄ in hepatocytes such as reduced protein and mucopolysaccharide content were markedly improved by the Cynara extract given at the dose of 120 mg/kg. Intracellular protein and mucopolysaccharide contents were normalized upon treatment with silymarin. The effect of Cynara–silymarin combination was, however, less than that of Cynara extract alone. These results suggest that treatment with Cynara extract protects against CCl₄-induced hepatic injury in rats and might prove of value in treating chronic liver disease in man, although the combination of Cynara–silymarin is not superior to either Cynara extract or silymarin alone.     

Investigation of relationship between idiopathic hypercalciuria and urinary enzyme activities

In patients with uncomplicated idiopathic hypercalciuria renal function is normal except for increased renal calcium excretion. In this study, the level of fractional urinary enzyme excretion was assessed in relation to calciuria. Fourteen patients with a mean age of 5.8 +/- 0.8 years who had daily urinary calcium excretion more than 4 mg/kg and with otherwise normal renal function tests were included in the study. None of the patients manifested either renal calculus or nephrocalcinosis. Fourteen normal children with a mean age of 5.4 +/- 0.74 were included in the control group. The level of the urinary N-acetyl beta-D glucosaminidase (NAG) to creatinine ratio, fractional aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) excretion were not significantly different compared to the control group (p > 0.05). The patients were subdivided according to the type of hypercalciuria. The levels of NAG/creatinine ratio, fractional ALT, AST, ALP, LDH excretion were not significantly different in the absorptive type of calciuria group compared to the control group (p > 0.05). In conclusion, hypercalciuria during childhood which is 6.46 +/- 1.83 mg/kg/day is not related to the levels of NAG/creatinine ratio, fractional ALT, AST, ALP and LDH excretion in urine.     

双下肢骨折大鼠血液粘度及血清酶活性变化

目的:观察骨折对大鼠血液流变学及血清酶学的影响。方法:20只Wistar大鼠,分为对照组、骨折组。观察双下肢骨折后血液流变学指标以及血清AST、ALT、LDH、LDH-1、HBDH、CK、CK-MB、ALP等指标的变化。结果:骨折组大鼠高、中、低切变率下全血粘度及血浆粘度均显著高于对照组,且血清LDH-1、CK-MB、ALP活性显著高于对照组(P<0.01),而血清AST、ALT、LDA、HBDA、CK活性与对照组无统计学差异(P>0.05)。结论:骨折可致大鼠血液流变性异常以及某些血清酶释放增多,从而引起器官功能障碍。     

Plasma biochemistry in pregnant Spanish purebred broodmares

The aim of this study was to determine if physiological changes occur in plasma total proteins (TPP) and albumin (ALB) concentrations and the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) in Spanish Purebred mares during pregnancy. Blood samples were collected by jugular puncture and anticoagulated in tubes with lithium heparin. In plasma obtained after centrifugation the concentrations of TPP and ALB and activities of AST, ALT, LDH, CK, ALP and GGT were determined by spectrophotometry. Pregnancy caused an increase in TPP and decrease in AST, CK and GGT (p?<?0.05) without modifications in ALB, ALT, LDH and ALP concentrations. Pregnancy has a significant influence on TPP, CK, GGT and AST dynamics in the mare, resulting in the development of reference ranges for this physiological condition. The decrease in values for plasma CK, AST, LDH and GGT enzymes activities during pregnancy should be considered a physiological condition related to pregnancy in the mare. It is important to know the direction and magnitude of these biochemical changes in pregnant mares, contributing to a better understanding of biochemical processes that occur in pregnant mares and providing practical help for the diagnosis of diseases that may present with similar biochemical findings.     

Comparative Adverse Effects Of Cox-1 and Cox-2 Inhibitors in Rat Liver: An Experimental Study."

The non-steroidal anti-inflammatory drugs (NSAIDs) do not reverse the disease process, but they provide much needed relief from pain and inflammation by inhibiting cyclooxygenase (COX) enzyme mediating the inflammatory pathway. NSAIDs cause number of death as a result of upper gastrointestinal damage. These agents also have unwanted effects on lower bowel, lungs, kidney and cardiovascular symptom. Coxibs are selective inhibitor of cyclooxygenase (COX)-2 and spares the COX-1 induced side effects i.e. gastric ulceration. Therefore in present study we compared the adverse effects of diclofenac sodium (diclo) a non-selective NSAID and valdecoxib (valde), a selective NSAID attherapeutic and subtherapeutic doses. Histological and biochemical changes of liver were observed. Beside that gross examination of the stomach mucosa for ulceration along lesser curvature too observed. For liver functions we estimated serum aspartate aminotransferase (AST), alknine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP). Experiment was carried out by administration of drugs for period of 30 days. Liver sections of diclo &; valde groups showed histological changes, which were more prominent with therapeutic dose of valde. The biochemical changes, subtherapeutic dose of diclo showed increase in ALP only. On the other hand subtherapeutic dose of valde showed significant changes in AST, high significant changes in LDH &; ALP Whereas therapeutic doses of diclo and valde showed highly significant increase in hepatic biochemical parameters i.e. AST, ALT, ALP, LDH.Thus it may conclude that higher doses of COX-1&;2 inhibitors can lead to acute hepatitis and other hepatic complications.     

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.     

Urantide对动脉粥样硬化大鼠肝功能及组织形态学的影响

目的:探讨urantide对动脉粥样硬化(AS)大鼠肝功能及组织形态学的影响。方法:采用腹腔注射维生素D3(VD3)及高脂饮食的方法复制Wistar大鼠AS模型,随机分为正常对照组、AS模型组、阳性药组和uran-tide组。生化分析仪检测各组大鼠肝功能指标;HE染色观察大鼠胸主动脉和肝脏的病理学变化;RT-qPCR和Western blot法检测大鼠肝脏中尾加压素Ⅱ(UII)及其受体GPR14的mRNA和蛋白表达水平。结果:AS模型组大鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ-谷氨酰转移酶(γ-GT)、乳酸脱氢酶(LDH)、总胆红素(TBIL)、间接胆红素(IBIL)和碱性磷酸酶(ALP)水平较正常对照组显著升高(P 0.05);urantide组大鼠上述各项指标较模型组均显著降低(P 0.05);各组血清中直接胆红素(DBIL)、总蛋白(TP)、球蛋白(GLB)和白蛋白(ALB)水平均无显著变化。Urantide可延缓AS大鼠肝细胞脂肪变性,修复肝细胞损伤。AS组大鼠肝脏中UII和GPR14mRNA及蛋白表达水平均较正常组显著增高(P 0.05);随着给药时间的延长,urantide治疗组大鼠肝脏中UII和GPR14 mRNA及蛋白表达水平较AS模型组显著降低(P 0.05)。结论:Urantide可明显减轻AS大鼠肝脂肪变性所引起的肝功能损伤。     

The protective effects of vitamin A in experimental myoglobinuric renal failure

The protective effects of vitamin A administration on renal failure in a rat model of rhabdomyolysis were investigated in this study. Three groups of rats (seven rats in each group) were employed in this study. Group 1 served as control, Gly group was given 50 % glycerol (7 mL/kg, I.M.), and Gly-Vit A group received glycerol and vitamin A daily (1,000 IU/kg, I.P.). Ninety-six hours after glycerol injection, blood samples were collected by heart puncture. Serum concentrations of creatinine, blood urea nitrogen (BUN), creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities were measured in serum samples. Histopathologic pattern of renal tissue damages was also evaluated. Gly-Vit A groups had lower serum concentrations of creatinine, LDH, and CK than the Gly group, and the administration of vitamin A decreased rhabdomyolysis induced renal tubular damages in Gly-Vit A group rather than in Gly group (P?相似文献   

Evaluation of the effects of methanol leaf extract of <Emphasis Type="Italic">Palisota hirsuta</Emphasis> on the biochemical and hematological parameters of rats

The effects of 28-day oral administration of the methanol leaf extract of Palisota hirsuta (MLEPH) on biochemical, hematological parameters, and relative organ weights (ROWs) in albino rats were investigated. There were no significant (p?>?0.05) variations in the ROW of the heart, kidney, spleen, and liver on days 14 and 28 in all the rats given the different doses of MLEPH. The hematology showed that there were no significant (p?>?0.05) alterations of the packed cell volume (PCV), hemoglobin concentration, RBC count, total white blood cell (tWBC), and differential WBC counts by MLEPH at 20, 40, 80, and 160 mg/kg when compared with control. The serum biochemistry also revealed no significant (p?>?0.05) variations in the serum activities of aspartate aminotransferase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (ALP), total protein, total bilirubin, and creatinine when the groups that received the extract at the different doses were compared with the control. Therefore, MLEPH did not cause significant toxicity after 28 days of oral administration.