Hepatoprotective effects of the nitric oxide donor isosorbide-5-mononitrate alone and in combination with the natural hepatoprotectant, silymarin, on carbon tetrachloride-induced hepatic injury in rats

Abdel-Salam, Omar M.E.; Sleem, Amany A.; Shafee, Nermeen

doi:10.1007/s10787-009-0027-7

Cited by 14 publications

(4 citation statements)

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“…Results from animal models applying CCl 4 as well as other hepatotoxic agents, e.g. paracetamol, show a significant change in hepatic acute phase enzymes and pro-fibrotic markers due to silymarin application (Table 2) [67,68]. In a further experiment in rats, using CCl 4 as the offending agent, a dose of 50 mg/ kg of silymarin was found to be more effective than 200 mg/kg in reducing oxidative stress, lysis of hepatocytes, activation of Kupffer cells, and the expression of alpha smooth muscle actin (α-SMA) and transforming growth factor beta 1 (TGF-β1) [54].…”

Section: Animal Modelsmentioning

confidence: 99%

The potential of silymarin for the treatment of hepatic disorders

et al. 2016

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Silymarin has long been used as a hepatoprotective remedy. Chronic toxicity studies in rodents have confirmed that silymarin has a very low toxicity. These data support its history as a safe medication in hepatic diseases. In the last years, several studies expanded our understanding of the pharmacology of silymarin and its molecular mechanisms of action. These new insights may affect the handling of silymarin in clinical studies and daily practice. Additionally, scientific knowledge in hepatology is constantly evolving with, particularly, an increase in the field of non-alcoholic fatty liver disease which is considered today as the most frequent liver disease worldwide. In this review, we will describe scientific evidence for the effectiveness of silymarin in hepatic disorders. We will focus on silymarin's pharmacological effects in non-alcoholic fatty liver disease and on its well described effects in alcoholic liver disease and acute intoxications, e.g. with Amanita species. We will discuss the relevance of pharmacological data as a function of doses or concentrations required for a given effect and of concentrations achieved in the target tissues. Many pharmacological effects of silymarin can be attributed to effects downstream or upstream of its antioxidative and membrane-stabilizing properties. However, despite promising new experimental and clinical data further clinical studies are required including long-term observations and the application of hard clinical endpoints such as survival rates, to further support silymarin's use for the treatment of hepatic diseases.

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Section: Animal Modelsmentioning

confidence: 99%

The potential of silymarin for the treatment of hepatic disorders

et al. 2016

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“…In different oncological diseases, such as prostate cancer, cervical cancer, hepatocellular carcinoma (HCC), bladder cancer and lung cancer, silymarin reduces cell vitality and runaway cell replication [ 48 , 49 , 50 , 51 , 52 ]. Because of its detoxifying power, its hydrosoluble endovenous formulation, it is used as an anti-hepatotoxic drug in poisonings due to acetaminophen, arsenic, carbon tetrachloride, butyrophenones, phenothiazines and Amanita phalloides toxins [ 53 , 54 , 55 , 56 ]. In hypercholesterolemia, silymarin inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, reducing cholesterol synthesis [ 57 ].…”

Section: Introductionmentioning

confidence: 99%

Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

2017

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Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.

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“…Salam et al reported that a dose of 7,2 mg · kg −1 ISMN applied by gastric gavage protected rats against hepatic injury and hepatocellular necrosis induced by carbon tetrachloride (see Additional file 1: Table S2) [31]. Therefore, we assumed that ISMN could also reduce the development of large confluent hepatocellular necrosis caused by outflow obstruction after extended liver resections and RHMV ligation [4].…”

Section: Discussionmentioning

confidence: 99%

Modulation of hepatic perfusion did not improve recovery from hepatic outflow obstruction

Arlt

Wei

Xie

et al. 2017

BMC Pharmacol Toxicol

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BackgroundFocal hepatic venous outflow obstruction frequently occurs after extended liver resection and leads to a portal hypertension, arterial hypoperfusion and parenchymal necrosis.In this study, we investigated the pharmacological modulation of liver perfusion and hepatic damage in a surgical model of hepatic outflow obstruction after extended liver resection by administration of 5 different drugs in comparison to an operative intervention, splenectomy.MethodsMale inbred Lewis rats (Lew/Crl) were subjected to right median hepatic vein ligation + 70% partial hepatectomy. Treatment consisted of a splenectomy or the application of saline, carvedilol or isosorbide-5-mononitrate (ISMN) (5 mg · kg−1 respectively 7,2 mg · kg−1 per gavage 12 h−1). The splenectomy was performed during operation. The effect of the treatments on hepatic hemodynamics were measured in non-operated animals, immediately after operation (n = 4/group) and 24 h after operation (n = 5/group). Assessment of hepatic damage (liver enzymes, histology) and liver cell proliferation (BrdU-immunohistochemistry) was performed 24 h after operation. Furthermore sildenafil (10 μg · kg−1 i.p. 12h−1), terlipressin (0.05 mg · kg−1 i.v. 12 h−1) and octreotide (10 μg · kg−1 s.c. 12 h−1) were investigated regarding their effect on hepatic hemodynamics and hepatic damage 24 h after operation (n = 4/group).ResultsCarvedilol and ISMN significantly decreased the portal pressure in normal non-operated rats from 11,1 ± 1,1 mmHg (normal rats) to 8,4 ± 0,3 mmHg (carvedilol) respectively 7,4 ± 1,8 mmHg (ISMN). ISMN substantially reduced surgery-induced portal hypertension from 15,4 ± 4,4 mmHg to 9,6 ± 2,3 mmHg. Only splenectomy reduced the portal flow immediately after operation by approximately 25%. No treatment had an immediate effect on the hepatic arterial perfusion. In all treatment groups, portal flow increased by approximately 3-fold within 24 h after operation, whereas hepatic arterial flow decreased substantially. Neither treatment reduced hepatic damage as assessed 24 h after operation. The distribution of proliferating cells appeared very similar in all drug treated groups and the splenectomy group.ConclusionTransient relative reduction of portal pressure did not result in a reduction of hepatic damage. This might be explained by the development of portal hyperperfusion which was accompanied by arterial hypoperfusion.Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-017-0155-4) contains supplementary material, which is available to authorized users.

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Hepatoprotective effects of the nitric oxide donor isosorbide-5-mononitrate alone and in combination with the natural hepatoprotectant, silymarin, on carbon tetrachloride-induced hepatic injury in rats

Cited by 14 publications

References 58 publications

The potential of silymarin for the treatment of hepatic disorders

The potential of silymarin for the treatment of hepatic disorders

Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

Modulation of hepatic perfusion did not improve recovery from hepatic outflow obstruction

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