Hepatoprotective effect of Spirulina platensis against carbon tetrachloride-induced liver injury in male rats.

OBJECTIVES: Spirulina platensis (SP) is an edible Cyanobacterium with ethnomedicinal significance. This study aims at evaluating the beneficial effect of SP against carbon tetrachloride (CCl4)-induced liver toxicity in male rats. METHODS: Rats received intraperitoneal injections of CCl4 (2 ml/kg body weight [b.w.] per every other day) for 40 days, alone or in combination with oral treatments of SP (400 mg/kg b.w. per day). KEY FINDINGS: SP attenuated haematological disturbances, serum liver markers, hepatic necrosis and inflammation, and dyslipidemia in CCl4-intoxicated rats. SP also reduced CCl4-induced oxidative stress by increasing the activities of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase and catalase and glutathione content, and inhibiting lipid peroxidation products and nitric oxide levels in the rat liver. Further investigations revealed that SP counteracted CCl4-induced increased hepatic levels of Ki-67 (a parameter of cell proliferation), interleukin-6, and tumour necrosis factor-alpha and cyclooxygenase-2 messenger RNA expression. Noticeably, the supplementation of SP restored the decrease of proapoptotic p53 protein levels in the liver of rats treated with CCl4. CONCLUSIONS: SP prevented liver damage in CCl4-treated rats via augmentation of antioxidant defense mechanisms and inhibition of inflammatory cytokines/mediators and antiproliferative effects.

Role of Anise on the hepatotoxicity induced by carbon tetrachloride in adult male albino rats

Oxidative stress induced by free radicals is known to be a common cause of liver damage and hepatic fibrosis. Anise oil and its compounds have been identified to have antioxidant, anti-inflammatory and antifibrinogenic properties that may play a role in the management of hepatic disorders and promote liver regeneration. Thus, the purpose of the study was to evaluate the effects of anise oil on hepatotoxicity induced by carbon tetrachloride in adult male albino rats. Sixty male albino rats were divided into control group, CCL4-treated group that was injected with 1 mg /kg CCL4 intraperitoneally (ip), CCL4+anise oil-treated group that was injected with 1 mg /kg of CCL4 and 0.5 ml/ kg of anise oil (ip), and anise oil-treated group that was injected with 0.5 ml/kg of anise oil. Animals received treatment for 4 weeks and sacrificed 24 hours after the last administration. Livers were removed and processed for light and electron microscopy analysis. The CCL4-treated group revealed loss of normal architecture of hepatic lobules, steatosis, necrosis, cholestasis, portal congestion and progressed grading of lobular inflammation, ballooning degeneration and fibrosis. On the other hand, the CCL4 + anise group showed reduced liver damage and increased signs of regeneration. We conclude that anise oil has a protective effect on liver damage caused by CCL4and promotes liver regeneration (AU)

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Renal replacement therapy in acute poisonings--one center experience.

The authors described three groups of patients after acute poisonings. In the first group were 60 patients after carbon tetrachioride poisoning, the second group consisted of 81 patients after mushroom poisoning and 20 patients after ethylene glycol poisoning were in the third group. Besides two patients with rare poisonings after potassium dichromate and after paraquat poisoning were analysed. All groups of patients with the kidney damage were presented from the diagnostic, differential diagnostic, conservative, ntra- and extracorporeal elimination treatment point of view. In the group of patients suffering from acute carbon tetrachloride poisoning and with acute renal failure following therapy was used: conservative treatment, exchange blood transfusion--in 4 patients in hepatic coma, renal replacement therapy (peritoneal dialysis, haemodialysis, plasmapheresis). From the total number of 60 patients 58 survived and 2 patients died in liver coma. Survival of patients after mushroom poisoning depended on amount of oral use of mushroom (Amanita phalloides), on early admission in dialysis centre and on early beginning of renal replacement therapy within 24 hr after acute poisoning. Twenty four patients from 81 patients of this group died. Main clinical signs of ethylene glycol poisoning were various neurological symptoms (cramps, hemiparesis, coma), severe metabolic acidosis (pH = 7.06 +/- 0.14), leucocytosis (26.4 +/- 5.5x 10(9)/L) and the signs of acute toxic hepatitis and of acute renal failure. Calcium oxalic crystals in urine were present in 17 patients and leucocytosis was observed in every patient. In the first 4 patients we administered intravenously ethylalcohol as an antidotum and later in other patients we used ethylalcohol in dialysis solution. The concentration of ethylalcohol in dialysis solution was 100 mg%. Severe metabolic acidosis improved in 17 patients using bicarbonate haemodialysis and 3 patients died before the possibility to use bicarbonate haemodialysis. Eighty-four hours after acute potassium dichromate poisoning and 24 hours after exchange blood transfusion during haemodialysis a 41-year old man died in haemorhagic shock, which developed after the extensive chemical burns of mucous membrane of gastrointestinal tract caused by this poison. Our patient after paraquat poisoning was treated by repeated charcoal haemoperfusion and haemodialysis. Despite of that therapy the patient died in severe respiratory insufficiency.

Downregulation effects of beta-elemene on the levels of plasma endotoxin, serum TNF-alpha, and hepatic CD14 expression in rats with liver fibrosis.

It has been demonstrated that ß-elemene could protect against carbon tetrachloride (CCl(4))-induced liver fibrosis in our laboratory work, and the aim of this paper is to reveal the protective mechanisms of ß-elemene. The hepatic fibrosis experimental model was induced by the hypodermical injection of CCl(4) in Wistar male rats. ß-elemene was intraperitoneally administered into rats for 8 weeks (0.1 mL/100 g bodyweight per day), and plasma endotoxin content was assayed by biochemistry. The serum TNF-α level was detected using radioactive immunity. CD14 expression in rat livers was measured by immunohistochemistry and Western blot. The results showed that ß-elemene can downregulate the levels of plasma endotoxins, serum TNF-α, and hepatic CD14 expression in rats with liver fibrosis. ß-elemene plays an important role in downregulating the lipopolysaccharide signal transduction pathway, a significant pathway in hepatic fibrosis development.

Hepatoprotective effect of pinoresinol on carbon tetrachloride-induced hepatic damage in mice.

Forsythiae Fructus is known to have diuretic, anti-bacterial, and anti-inflammatory activities. This study examined the hepatoprotective effects of pinoresinol, a lignan isolated from Forsythiae Fructus, against carbon tetrachloride (CCl(4))-induced liver injury. Mice were treated intraperitoneally with vehicle or pinoresinol (25, 50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20 microl/kg) injection. In the vehicle-treated CCl(4 )group, serum aminotransferase activities were significantly increased 24 h after CCl4 injection, and these increases were attenuated by pinoresinol at all doses. Hepatic glutathione contents were significantly decreased and lipid peroxidation was increased after CCl4 treatment. These changes were attenuated by 50 and 100 mg/kg of pinoresinol. The levels of protein and mRNA expression of inflammatory mediators, including tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2, were significantly increased after CCl4 injection; and these increases were attenuated by pinoresinol. Nuclear translocation of nuclear factor-kappaB (NF-kappaB) and phosphorylation of c-Jun, one of the components of activating protein 1 (AP-1), were inhibited by pinoresinol. Our results suggest that pinoresinol ameliorates CCl4)-induced acute liver injury, and this protection is likely due to anti-oxidative activity and down-regulation of inflammatory mediators through inhibition of NF-kappaB and AP-1.

In vitro and in vivo antifibrotic effects of rosmarinic acid on experimental liver fibrosis.

This study was carried out to investigate whether rosmarinic acid (RA) has antifibrotic effect on experimental liver fibrosis in vitro and in vivo and its possible mechanism. Culture of hepatic stellate cells (HSCs) determine proliferation and expression of transforming growth factor-beta1 (TGF-beta1), connective transforming growth factor (CTGF) and alpha-smooth muscle actin (alpha-SMA). In carbon tetrachloride (CCL(4))-induced rat liver fibrosis model, determined biochemical indicator, liver fibrosis grade and histopathological changes, immunohistochemical detected liver TGF-beta1 and CTGF expression. The results indicated that RA could inhibit HSCs proliferation, inhibit TGF-beta1, CTGF and alpha-SMA expression in cultured HSCs. It has marked evident in reducing fibrosis grade, ameliorating biochemical indicator and histopathological morphology, reducing liver TGF-beta1 and CTGF expression in CCL(4)-induced liver fibrosis. These findings suggest that RA has potentially conferring antifibrogenic effects.

Potential therapeutic effects of a traditional Chinese formulation, BJ-JN, on liver fibrosis induced by carbon tetrachloride in rats.

AIM OF THE STUDY: To evaluate the anti-fibrotic effects of BJ-JN (a traditional Chinese formulation) in CCl(4)-induced liver fibrosis in rats. MATERIALS AND METHODS: BJ-JN (0.5, 1.0, 2.0 g/kg) was administrated via gavage once a day starting from the fifth weeks after the CCl(4) treatment for subsequent 9 weeks. Evaluated with liver and spleen index, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), nitric oxide (NO), hepatic malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, as well as with histopathologic changes of liver. The proliferation and collagen synthesis of primary hepatic stellate cells (HSCs) from normal, model and BJ-JN (2.0 g/kg) treatment rats were examined with (3)H-TdR and (3)H-Pro uptake assay, respectively. RESULTS: BJ-JN (0.5, 1.0, 2.0 g/kg) effectively reduced the elevated levels of liver and spleen index, serum ALT, AST, NO, HA, and hepatic MDA contents, enhance the reduced hepatic SOD activity in CCl(4)-treated rats. The histopathological analysis suggested that BJ-JN obviously alleviated the degree of liver fibrosis induced by CCl(4). The proliferation and collagen synthesis of HSC isolated from BJ-JN (2.0 g/kg) treatment rats were remarkably inhibited. CONCLUSIONS: Those results suggest BJ-JN has a protective and therapeutic effect on liver fibrosis induced by CCl(4), which might be associated with its anti-oxidative activity, inhibitory activity on HSC proliferation and collagen synthesis.

Effect of the administration of fermentable and non-fermentable dietary fibre on intestinal bacterial translocation in ascitic cirrhotic rats.

BACKGROUND: Bacterial infections are frequent in cirrhosis. Experimental studies suggest a pathogenic role of intestinal bacterial translocation in them. Both fermentable and non-fermentable fibre avoided intestinal bacterial translocation (IBT) in animal models of gut starvation and critical illness. AIM: To assess the effect of fermentable (pectin) or non-fermentable (lignin) fibre on IBT in ascitic cirrhotic rats. METHODS: Thirty-six rats induced to cirrhosis with oral CCl4 were randomized (6 weeks after the first CCl4 dose) to receive rat chow+5% lignin (LIG, n=13), rat chow+5% pectin (PEC, n=13), or rat chow only (CON, n=10). Once ascites developed, animals were laparotomized and samples of mesenteric lymph nodes (MLN), ascitic fluid, portal and peripheral blood and liver, were obtained for culture. RESULTS: IBT rate was: LIG=5/13, PEC=4/13, CON=5/10 (P=N.S.). The median amount of translocated bacteria in rats with IBT was lower in the PEC group (2 x 10(2) CFU/g MLN), than in LIG (10(5) CFU/g MLN) and CON (10(4) CFU/g MLN) groups (P<0.05). All other samples were sterile except for a portal blood sample (Enterococcus faecalis) of the LIG group. CONCLUSIONS: IBT incidence is not decreased by either pectin or lignin in ascitic cirrhotic rats, but pectin supplementation reduces the amount of translocated bacteria.

Protective effect of Indigofera aspalathoides against CCl4-induced hepatic damage in rats.

The alcoholic extract of stem of Indigofera aspalathoides was evaluated for its antihepatotoxic activity against CCl(4)-induced hepatic damage in rats. The activity was evaluated by using biochemical parameters, such as serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin and gama glutamate transpeptidase (GGTP). The histopathological changes of liver sample were compared with respective control. The extract showed remarkable hepatoprotective effect.

Effects of post low-dose X-ray irradiation on carbon tetrachloride-induced acatalasemic mice liver damage.

The catalase activities in the blood and organs of the acatalasemic (C3H/AnLCsb-Csb) mouse of the C3H strain are lower than those of the normal (C3H/AnLCSa-Csa) mouse. We examined the effects of post low-dose (0.5 Gy) X-ray irradiation which reduced the oxidative damage under carbon tetrachloride-induced hepatopathy in acatalasemic or normal mice. As a result, the 0.5 Gy irradiation after carbon tetrachloride administration decreased the glutamic oxaloacetic and glutamic pyruvic transaminase activity in the acatalasemic mouse blood to a level similar to that of the acatalasemic mouse blood not treated with carbon tetrachloride; this is in contrast to a high-dose (15 Gy) irradiation. In the same manner, pathological disorder was improved by 0.5 Gy irradiation. The fat degeneration in normal mice was quickly reduced, in contrast to acatalasemic mice. These findings suggest that low-dose irradiation after carbon tetrachloride administration accelerates the rate of recovery and that catalase plays an important role in the recovery from hepatopathy induced by carbon tetrachloride, in contrast to high-dose irradiation.

Protective effect of Lycium chinense fruit on carbon tetrachloride-induced hepatotoxicity.

In the present study, we investigated the protective effect of Lycium chinense Miller (Solanaceae) fruit (LFE) against CCl(4)-induced hepatotoxicity and the mechanism underlying these protective effects in rats. The pretreatment of LFE has shown to possess a significant protective effect by lowering the serum aspartate and alanine aminotransferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation. In addition, pretreatment of LFE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CCl(4)-injected rats. The LFE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC(50) = 83.6 microg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. The expression level of cytochrome P450 2E1 (CYP2E1) mRNA and protein, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis, was significantly decreased in the liver of LFE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the LFE might be related to antioxidative activity and expressional regulation of CYP2E1.

[Pathological study of the therapeutic effect of wen-yang herbs on experimental liver cirrhosis].

OBJECTIVE: To observe the pathological effect of wen-yang herbs on experimental hepatic fibrosis. METHODS: Thirty-two male Wistar rats were used in this study comprising four groups. To start with, 24 rats of three groups were given subcutaneous injection of CCl4 and drinking 10% alcohol so as to make the model of hepatic fibrosis. After the establishment of the pathologic model, the rats were divided into the model group, the pathological control group and the therapeutic group by randomization. The rats of the therapeutic group were given the herbal remedies via gastrogavage, q.d. x 30. The rats of the pathological control group were given normal saline via gastrogavage, q.d. x 30. Then liver tissue Hydroxyproline (Hyp) content was examined in these 3 groups and the normal group. Quantitative marks were done according to a modified semiquantitative scoring system (SSS). The results of SSS marks and Hyp contents were analysed using Pearson's coefficient of correlation. RESULTS: The Hyp content and SSS marks of the therapeutic group decreased remarkably as compared with those of the control group (P<0.01), and the SSS marks had a strong positive correlation with Hyp content (r=0.804). CONCLUSION: Wen-yang herbs can mitigate the rats' hepatic fibrosis and promote a recovery of their experimental illness.

[Therapeutic effect of "anti-hepatic-fibrosis 268" on hepatic fibrosis in rats].

OBJECTIVE: To investigate the effects of the proprietary Chinese Medicine "anti-hepatic-fibrosis 268" on hepatic fibrosis and the related mechanisms. METHODS: The model of CCl4-induced hepatic damage was established in SD rats. 54 male rats were divided into four groups, namely high dose and low dose "anti-hepatic-fibrosis 268" groups, colchicine control group, and model control group. Using Masson stain and light microscope, the authors examined the rats' hepatic tissues and counted the hepatic fiber components, then examined and counted TGF-beta1, alpha-SMA, FN, Type I, III collagen by means of immunohistochemical technique. The groups were compared and the internal relationships of the data were analyzed. RESULTS: The levels of FN, LN, Type I and III collagen, TGF-beta1, and alpha-SMA of the CCl4 damaged rats increased (P<0.01). After 3 weeks of high dose "anti-hepatic-fibrosis 268" treatment, the levels of TGF-beta1, alpha-SMA, FN, LN, Type I and III collagen decreased (P<0.01) and the degree hepatic fibrosis took a favorable turn significantly (P<0.05) as compared with the model control. In the rats of the low dose group, the levels of TGF-beta1, alpha-SMA, FN, Type III collagen significantly decreased (P<0.05), the levels of LN, Type I collagen were not different from the model control; The hepatic fibrosis improved to a certain extent (P<0.05). CONCLUSION: The mechanism of reversing hepatic fibrosis by "anti-hepatic-fibrosis 268" in this experiment is that the medicine regulates TGF-beta1 and further affects alpha-SMA, thus resulting in the decline of FN, Type I, III collagen levels in liver extracellular matrix.

[Antioxidant action of oligomeric proanthocyanidins isolated from viburnum in liver lesions by carbon tetrachloride and prevention of the latter's toxicity]. / Antioksidantnoe deistvie oligomernykh proantotsianidinov, vydelennykh iz kaliny, pri porazhenii pecheni chetyrekhkhloristym uglerodom i profilaktike ego toksicheskogo éffekta.

The effect of a set of oligomeric anthocyanidins, isolated from viburnum, produced on the indices of lipid metabolism, lipid peroxidation (LPO) and on the hepatic antioxidant system in rats, who were subjected to the impact of carbon tetrachloride (CTC), was studied versus such effect exerted by preparations "Piknogenol" and "Legalon". The set of oligomeric anthocyanidins had a pronounced antitoxic and antioxidant action preventing the development of fat infiltration of the liver. The discussed preparation inhibited the processes of LPO, it normalized the level of antiradical hepatic activity and had a pronounced glutathione-saving effect, which is preconditioned by the biological activity of oligomeric anthocyanidins (traps for free radicals). The preparation can be used in prevention and treatment of toxic hepatic lesions.

Hepatoprotective activity of Trichilia roka on carbon tetrachloride-induced liver damage in rats.

Trichilia roka Chiov. (Meliaceae) is a tree widely distributed in tropical Africa. It has been used in Mali folk medicine for the treatment of various illnesses. A decoction of the roots is taken as a remedy for colds and pneumonia, and it is used as a diuretic and in hepatic disorders. We have evaluated the hepatoprotective effects of a decoction of Trichilia roka root on CCl4-induced acute liver damage in rats. Treatment with the decoction showed a significant protective action made evident by its effect on the levels of glutamate oxalacetate transaminase and glutamate pyruvate transaminase in the serum, on the protein content and lipid peroxidation levels in the liver homogenate. Histopathological changes produced by CCl4, such as necrosis, fatty change, ballooning degeneration and inflammatory infiltration of lymphocytes around the central veins, were clearly recovered by the treatment with Trichilia root decoction. On fractionating this extract into diethyl ether-soluble and water-soluble fractions, the activity was retained in the diethyl ether-soluble fraction. Moreover, the administration of decoction prevented a preferential deposition of collagen around the sinusoidal cell layer, which is responsible for the perisinusoidal fibrosis in the early stage of CCl4 damage. This study showed that treatment with Trichilia roka extracts or silymarin (as reference) appeared to enhance the recovery from CCl4-induced hepatotoxicity. The hepatoprotective properties of Trichilia roka may be correlated to polyphenol content of the decoction and its diethyl ether-soluble fraction.

Hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, on carbon tetrachloride-intoxicated rats.

The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against carbon tetrachloride (CCl(4))-induced liver damage in rats. Bergenin at a dose of 50, 100 or 200 mg/kg was administered orally once daily for successive 7 days and then a mixture of 0.5 ml/kg (ip) of CCl(4) in olive oil (1:1) was injected two times each at 12 and 36 h after the final administration of bergenin. The substantially elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma-glutamyltransferase due to CCl(4) treatment were dose dependently restored towards normalization. Meanwhile, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. In addition, bergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl(4)-intoxicated rats in a dose dependent fashion. The results of this study clearly indicate that bergenin has a potent hepatoprotective action against CCl(4)-induced hepatic damage in rats.

Antihepatotoxic activity of bergenin, the major constituent of Mallotus japonicus, on carbon tetrachloride-intoxicated hepatocytes.

To determine the antihepatotoxic activity of bergenin from Mallotus japonicus, carbon tetrachloride (CCl4)-induced cytotoxicity in primary cultured rat hepatocytes has been adopted as an assay system. Bergenin significantly reduced the activities of glutamic pyruvic transaminase and sorbitol dehydrogenase released from the CCl4-intoxicated hepatocytes. The antihepatotoxicity of bergenin was also evidenced by elevating the activities of glutathione S-transferase and glutathione reductase, and content of glutathione in the CCl4-intoxicated hepatocytes. From these results, it is assumed that bergenin exerted antihepatotoxicity against CCl4-induced cytotoxicity through glutathione-mediated detoxification as well as free radical suppressing activity.

[The specific activity of new drug forms of dibunol]. / Spetsificheskaia aktivnost' novykh lekarstvennykh form dibunola.

The specific activity of new drug forms (tablets, suppositories, ointments) of dubinal was studies on models of ischemic damage to the heart, toxic hepatitis, aseptic inflammation, damage to the skin and mucosa of the large intestine. It was found that the drug forms under study possessed a cardioprotective, hepatoprotective, anti-inflammatory, and wound-healing effect. This may serve as a prerequisite to their further clinical study.

[The joint use of prednisolone and phospholipid-containing hepatoprotectors in experimental chronic hepatitis]. / Sovmestnoe primenenie prednizolona i gepatoprotektorov, soderzhashchikh fosfolipidy, pri éksperimental'nom khronicheskom gepatite.

In chronic CCl4-hepatitis in rats phospholipid-containing hepatoprotectors, essentiale and eplir differ in their influence on the therapeutic effect of prednisolone; essentiale does not change the antiproliferative effect of the glucocorticoid and weakens its membrane-stabilizing effect, eplir increases these therapeutic effects of prednisolone. Besides, eplir, in distinction from essentiale, reduces lipid accumulation in the liver and hypoproteinemia which are induced by prednisolone.

[Effect and mechanism of action of Tinospora bakis roots on biliary secretion using in vivo models]. / Etude de l'effet et du mécanisme d'action des racines de Tinospora bakis sur la sécrétion biliaire àpartir de modèles in vivo.

The aim of this study is to determine the choleretic properties of lyophilized aqueous extract of Tinospora bakis roots. For thus, we have used healthy and cholestatic Wistar rats. After administration of the extract (4 mg/100 g of weight) biliary flow, biliary acids flow, biliary glutathione and glucose concentrations were measured by specific methods. Comparative results between treated rats and non treated rats show: For healthy rats: a significant increase of biliary flow, biliary acids flow in the group of treated rats versus non treated healthy rats. There were no significant difference in the glutathione and glucose concentrations. For cholestatic rats: we noted also significant increase of biliary flow, biliary acids flow and glutathione concentration in the treated rats group. These results suggest that Tinospora bakis has a choleretic effect in vivo which depends on biliary acids and/or glutathione concentration.