Qi Sui Zhu Shui Plaster Inhibits AQP1 and MAPK Signaling Reduces Liver Damage Induced by Cirrhotic Ascites.

Objective: At present, there is no special treatment for cirrhotic ascites in modern medicine. Qi Sui Zhu Shui plaster (QSZSP) has been used in ascites. The purpose of this study was to investigate the mechanism of action of QSZSP in the treatment of cirrhotic ascites and its relationship with aquaporin 1 (AQP1). Methods: Twenty-four rats were divided into four groups, six rats in each group. Carbon tetrachloride-olive oil is injected into modeling. The control and model groups are treated with blank gel plaster (2 cm × 2 cm), QSZSP low-dose group is treated with Qi Sui Zhu Shui plaster (1 cm × 1 cm), and QSZSP high-dose group is treated with Qi Sui Zhu Shui plaster (2 cm × 2 cm). The changes in body weight and abdominal circumference were measured, the histopathological changes in liver, kidney, and peritoneum were observed in HE staining, the biochemical indexes related to liver function were detected, and the changes in AQP1 expression and the activation of MAPK pathway in the liver, kidney, and peritoneal tissues were evaluated in IHC staining and Western blot. Results: After one week of injection of carbon tetrachloride-olive oil, the rats in the model group increased their body weight slowly, the abdominal circumference of the model rats continued to increase with time. After 16 weeks of construction of the cirrhotic ascites model, the liver, kidney, and peritoneum were significantly damaged, and the serum levels of TBiL, AST, ALT, Cr, BUN, K, Na, and Ca in the rats were significantly higher (P < 0.001) and ALB levels were significantly lower (P < 0.001) than those in the control group. After 4 weeks of treatment, the liver, kidney, and peritoneal injury were improved. TBiL, AST, ALT, Cr, BUN, K, Na, and Ca levels were significantly lower (P < 0.001) and ALB levels were significantly higher (P < 0.001) than those in the model group. The protein expression of AQP1, p-ERK, p-JNK, and p-p38 was found to be inhibited in the liver, kidney, and peritoneum. Conclusion: QSZSP inhibits the protein expression of AQP1 and MAPK signaling pathway in the liver, peritoneum, and kidney to alleviate liver, kidney, and peritoneal injury caused by cirrhotic ascites, thus reducing the abnormal growth of abdominal circumference.

Metformin versus silymarin as hepatoprotective agents in mice fibrotic model caused by carbon tetrachloride.

OBJECTIVES: To study metformin hepatoprotective effects compared to silymarin on hepatic fibrosis caused by carbon tetrachloride (CCl4) in mice. MATERIAL AND METHODS: Liver fibrosis in mice was achieved by intraperitoneal injection of 2mL/kg of CCl4 dilution in olive oil [1:9 (v/v)] twice a week for 7 weeks followed by oral treatment with metformin (250mg/kg/day) or silymarin (100mg/kg/day) (a standard hepatoprotective drug). The changes that follow liver fibrosis were assessed by measurement of hepatic enzymes (ALT, AST and ALP), histopathological examination using hematoxylin and eosin stain, special stains, and α-smooth muscle actin (α-SMA) immunostaining, measuring oxidative stress markers (MDA, GSH, NOx and MnSOD) and transforming growth factor-beta 1 (TGF-ß1) in liver. RESULTS: Liver fibrosis was obviously developed in mice after intraperitoneal injection with CCl4 for 7 weeks. Both silymarin and metformin treatment exhibited a significant decrease in the fibrotic changes and similarly an increase in endogenous antioxidants. Interestingly there is a significant difference between silymarin and metformin regarding both efficacy and potency. CONCLUSION: These findings highlight the anti-inflammatory, antioxidant and antifibrotic effects of metformin in CCl4-induced hepatic fibrosis in mice, but silymarin is more beneficial.

Mesenchymal stem cells overexpressing hepatocyte nuclear factor-4 alpha alleviate liver injury by modulating anti-inflammatory functions in mice.

BACKGROUND: Mesenchymal stem cells (MSCs) can migrate to tissue injury sites where they can induce multipotential differentiation and anti-inflammation effects to treat tissue injury. When traditional therapeutic methods do not work, MSCs are considered to be one of the best candidates for cell therapy. MSCs have been used for treating several injury- and inflammation-associated diseases, including liver cirrhosis. However, the therapeutic effect of MSCs is limited. In some cases, the anti-inflammatory function of naïve MSCs is not enough to rescue tissue injury. METHODS: Carbon tetrachloride (CCl4) was used to establish a mouse liver cirrhosis model. Enhanced green fluorescence protein (EGFP) and hepatocyte nuclear factor-4α (HNF-4α) overexpression adenoviruses were used to modify MSCs. Three weeks after liver injury induction, mice were injected with bone marrow MSCs via their tail vein. The mice were then sacrificed 3 weeks after MSC injection. Liver injury was evaluated by measuring glutamic-pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST) levels. Histological and molecular evaluations were performed to study the mechanisms. RESULTS: We found that HNF-4α-overexpressing MSCs had a better treatment effect than unmodified MSCs on liver cirrhosis. In the CCl4-induced mouse liver injury model, we found that HNF-4α-MSCs reduced inflammation in the liver and alleviated liver injury. In addition, we found that HNF-4α promoted the anti-inflammatory effect of MSCs by enhancing nitric oxide synthase (iNOS) expression, which was dependent on the nuclear factor kappa B (NF-κB) signalling pathway. CONCLUSIONS: MSCs overexpressing HNF-4α exerted good therapeutic effects against mouse liver cirrhosis due to an enhanced anti-inflammatory effect. Gene modification is likely a promising method for improving the effects of cell therapy.

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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Tratamento homeopático da hepatotoxicose aguda induzida por tetracloreto de carbono em coelhos / Homeopatic treatment of acute carbon tetrachloride induced hepatotoxicity in rabbits

Quinze (15) coelhos (Oryctolagus cuniculus) foram submetidos à intoxicaçäo pelo tetracloreto de carbono na dosagem de 0,5 ml/kg de peso corporal, dose única, administrado por sonda gástrica. Foram realizadas as dosagens de alanina amino tranferase (ALT), aspartato amino transferase (AST), fosfatase alcalina (FA) e gama glutamil tranferase (GGT) antes e durante o experimento. Vinte e quatro (24) horas após a intoxicaçäo, os coelhos foram divididos aleatoriamente em três grupos de 5 animais. Cada grupo recebeu um tratamento diferente durante 13 dias. O grupo I foi tratado com tetracloreto de carbono diluído na 30ª centesimal hahnemanniana (30 CH), uma vez ao dia. O grupo II recebeu Phosphorus 30 CH, também uma vez ao dia. O grupo III desempenhou o papel de controle, recebendo diariamente uma dose de placebo, pelo mesmo período de tempo que os grupos anteriores. Os resultados das concentraçöes séricas de ALT, AST, GGT e FA foram submetidos à análise estatística. A variaçäo da concentraçäo de todas as enzimas foi significativa entre os dias, mas nem todas variaram significativamente entre os grupos considerados. O tetracloreto de carbono 30 CH foi capaz de acelerar a recuperaçäo do quadro de hepatite tóxica aguda determinada pela reduçäo dos níveis de ALT. O tratamento com Phosphorus 30 CH mostrou-se incapaz seja de reverter o quadro de hepatite tóxica, seja de acelerar a regeneraçäo hepática.

Efeito do pós-tratamento com o extrato bruto hidroalcoólico desidratado de solanum paniculatum L. em lesöes hepáticas induzidas pelo tetracloreto de carbono / Post-treatment effect with dehydrated hydroalcoholic crude extract of solanum paniculatum L. on induced hepatic lesion by carbon tetrachloride

A espécie vegetal Solanum paniculatum l. (Solanaceae), vulgarmente conhecida no Brasil como gerobeba, joá-manso, jubeba, jupeba, juribeba, juripeba, jurubeba, jurubeba-verdadeira, jurubebinha, jurupeba, tem sido empregada empiricamente pela populaçäo há mais de um século na prevençäo e tratamento de moléstias hepáticas. No presente estudo, foram administradas duas doses de extrato bruto hidroalcoólico desidratado (EHD), obtido a partir do caule, folhas e flores, por via intragástrica, a ratos previamente submetidos a lesäo hepática, tendo-se utilizado como toxina padräo o tetracloreto de carbono (CCl4). Como marcadores da morfofuncionalidade hepática, foram utilizados parâmetros histopatológicos (inflamaçäo, esteatose, necrose e degeneraçäo hidrópica dos hepatócitos) e bioquímicos (aspartato aminotransferase (AST), alanina aminotransferase (ALT), bilirrubina total (BILTOT), bilirrubina direta (BILDIR) e bilirrubina indireta (BILIND). Os achados bioquímicos de AST e ALT revelaram que a administraçäo posterior do EHD, em ambas as doses, näo foi capaz de alterar a rota de lesäo hepática induzida pelo CCl4, contudo as concentraçöes de BILTOT e BILIND se mostraram estatisticamente superiores quando comparadas àquelas encontradas nos animais tratados somente com CCl4, indicando um possível efeito potencializador nas lesöes hepáticas induzidas por esta hepatotoxina. Histologicamente, os cortes dos animais controle em relaçäo aos tratados com os EHD näo se mostraram diferentes, no que diz respeito à inflamaçäo, esteatose, necrose e degeneraçäo hidrópica dos hepatócitos. Conclui-se que o tratamento posterior com o EHD de Solanum paniculatum L. näo foi eficaz na reversäo de lesöes hepáticas induzidas pelo CCl4, näo se encontrando justificativa científica para sua utilizaçäo como agente hepatoprotetor através do presente protocolo experimental.

Hematological and blood pressure studies in the CCl4 treated rats.

Hematological parameters were studied in normotensive and spontaneous hypertensive rats along with those treated with chronic subcutaneous injections of CCl4. The normotensive animals treated with CCl4 demonstrated an erythrocytosis with an increase in the hematocrit levels. A lymphocytosis was seen with neutropenia in both CCl4 treated and untreated normotensive groups. The SHR animals compared to their normotensive counterparts had a lesser degree of lymphocytosis with an increase in the number of neutrophils. There was no blood pressure change in the normotensive CCl4 treated group, however a significant blood pressure difference was observed in the SHR group after CCl4 treatment.

[Lipid peroxidation in the rat liver after acute inflammation induced by carrageenan. I. Influence of non-steroidal anti-inflammatory agents]. / Perossidazione lipidica nel fegato di ratto dopo flogosi acuta indotta da carragenina. 1. Influenza di alcuni farmaci anti-inflammatori non steroidei.

Oral administration of Indomethacin (3 mg/Kg) and Phenylbutazone (200 mg/Kg) induces an increase of TBA reacting substances (TBArs) by total liver homogenates, while treatment with Ibuprofen(200 mg/Kg, os) does not affect the susceptibility of liver tissue to lipid peroxidation. The former compounds do not influence the pro-oxidant action of CCl4 (1,0 ml/Kg, os) as evaluated "in vitro", whereas Ibuprofen appears to limit the extension of the TBArs production induced by the halomethane. The acute inflammatory state determined by carrageenan injection in the rat hind paw does not interfere with the peroxidative derangement found "in vitro" neither in the presence or in the absence of the all mentioned chemicals. Carbon tetrachloride (1,0 ml/Kg, os) is able in depressing significantly the rat paw oedema provoked by carrageenan, but does not potentiates the anti-inflammatory action of non-steroid agents.

[Experimental basis for the therapy of Amanita phalloides poisoning]. / Experimentelle Grundlagen zur Therapie von Vergiftungen durch den grünen Knollenblätterpilz (Amanita phalloides).

The experimental basis for the treatment of death-cap poisoning is reviewed. The available data suggest penicillin and silymarin as the antidotes most likely to be effective. Measures to increase the elimination of the toxins appear to be warranted.

Antagonistic effects against single lethal doses of Amanita phalloides.

Agents with antagonistic effects against phalloidin or alpha-amanitin were tested in mice against lethal doses of an extract from the whole mushroom Amanita phalloides. The following categories of agents reduced lethality after the extract. First, agents protecting only against phalloidin such as rifampicin, phenylbutazone and antamanide. Second, silymarin and prednisolone which display both antiamatoxic and marked (silymarin) or moderate (prednisolone) anti-phallotoxic acitivty. Thioctic acid displayed some activity when tested against mid-lethal doses of the extract. Cytochrome c, a chemical with curative potencies against alpha-amanitin did not reduce the lethality of the exact. All of the effective agents acted only when applied prior to the poisoning. The pattern or protective activity would indicate that in mice death after single doses of Amanita phalloides may follow a qualitatively particular couse which is difficult to ascribe to phallo- or amatoxic effects alone.

[Two cases of external ophthalmomyasis (author's transl)]. / Zwei Fälle von Ophthalmomyasis externa

After a brief survey of Hungarian references the author reports on two cases of ophthalmomyasis externa. The organism was shown to be present oestrus ovis in one instance. The treatment with carbon-tetrachloride might be considered as a new and efficacious therapy.