Deleterious effects of silymarin on the expression of genes controlling endothelial nitric oxide synthase activity in carbon tetrachloride-treated rat livers

Cho, Yong Kyun; Yun, Jung Won; Park, Jung Ho; Kim, Hong Joo; Park, Dong Il; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik; Jin, Wook; Kwon, Yong Hyun; Shin, Mikyung; Yoo, Tae Moo; Kang, Ju‐Hee; Park, Chang‐Shin

doi:10.1016/j.lfs.2009.06.001

Cited by 14 publications

(16 citation statements)

References 54 publications

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“…Therefore, serum ALAT is more specific to the liver, and is thus a better parameter for detecting liver injury (Williamson et al, 1996). In conjunction with the reports of (Cho et al, 2009;Hegde and Joshi, 2009;Kim et al, 2010), data from the present study showed that CCl 4 caused hepatic damage with a significant increase in serum levels of ASAT and ALAT. Serum ALP level is also related to the status and function of hepatic cells.…”

Section: Discussionsupporting

confidence: 91%

The effects of Honey and Aloe Vera extract on Ibuprofen Induced Liver Damage in rats.

Mohammed¹,

Garba²,

Numan³

et al. 2012

IOSJPBS

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This study was designed to determine the effect of Aloe Vera extract and honey against ibuprofen induced liver damage in albino rats. A total of twenty five (25) adult male albino rats weighing 100-150g were divided into five groups (I, II, III, IV and V) of five rats each. Rats in group I served as control and were administered normal saline in a volume equivalent to the highest dosed group, rats in group II were administered 100mgkg -1 of ibuprofen, rats in group III were administered 100mgkg -1 of ibuprofen and 10 gkg -1 of Aloe Vera extract , rats in group IV were administered 100mgkg -1 of ibuprofen and 10 gkg -1 of honey while rats in group V were administered with 100mgkg -1 of ibuprofen , 10 gkg -1 of Aloe Vera extract and 10 gkg -1 of honey orally. The result showed a slight increase in liver weight, a significant increase (P<0.05) in the levels of Aspartate minotransferases (ASAT) , Alanine aminotransferases (ALAT) and Alkaline phosphatase (ALP) in the ibuprofen treated rats when compared to the control rats. Administration of Aloe vera extract and honey did not reverse the damage caused. Histological findings indicate severe dilation of blood vessel, necrosis of vascular connective tissues, wide spread vacuolar degeneration, edema and bile duct hyperplasia. The result indicates that Aloe vera extract and honey has little or no effect in preventing ibuprofen induced toxicity.

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Section: Discussionsupporting

confidence: 91%

The effects of Honey and Aloe Vera extract on Ibuprofen Induced Liver Damage in rats.

Mohammed¹,

Garba²,

Numan³

et al. 2012

IOSJPBS

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“…Silymarin restored the elevated level of serum ALT in CCl 4 intoxicated rats [44] and in diethylnitrosamine administered rats [45] by preventing liver damage through maintaining the integrity of the plasma membrane, thereby suppressing the leakage of enzymes. The increase in the hepatic GSH content may be attributed to the well established antioxidant actions of silymarin [39], which was able to dramatically reduce the generation of intracellular ROS in response to different pro-oxidant stimuli [42].…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis

et al. 2012

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BackgroundPraziquantel (PZQ) is an isoquinoline derivative (2-cyclohexylcarbonyl-1, 2, 3, 6, 7, 11b-hexahydro-4H-pyrazino{2,1-a}-isoquinoline-4-one), and is currently the drug of choice for all forms of schistosomiasis. Silymarin, a standardized milk thistle extract, of which silibinin is the main component, is known for its hepatoprotective, anti-inflammatory, antioxidant activities, and hepatocyte regeneration. This study investigates the anti-inflammatory/anti-fibrotic effects of silymarin and/or PZQ on schistosomal hepatic fibrosis.MethodsSchistosoma mansoni-infected mice were divided into two large groups (I & II), each with four subgroups and were run in parallel. (i) Infected untreated; (ii) treated with silymarin, starting from the 4th (3 weeks before PZQ therapy) or 12th (5 weeks after PZQ therapy) weeks post infection (PI); (iii) treated with PZQ in the 7th week PI; and (iv) treated with silymarin, as group (ii) plus PZQ as group (iii). Comparable groups of uninfected mice run in parallel with the infected groups. Mice of groups I and II were killed 10 and 18 weeks PI, respectively. Hepatic content of hydroxyproline (HYP), serum levels and tissue expression of matrix metalloproteinase-2 (MMP-2), transforming growth factor-β1 (TGF-β1) and number of mast cells were determined. In addition, parasitological, biochemical and histological parameters that reflect disease severity and morbidity were examined.ResultsSilymarin caused a partial decrease in worm burden; hepatic tissue egg load, with an increase in percentage of dead eggs; modulation of granuloma size, with significant reduction of hepatic HYP content; tissue expression of MMP-2, TGF-β1; number of mast cells, with conservation of hepatic reduced glutathione (GSH). PZQ produced complete eradication of worms, eggs and alleviated liver inflammation and fibrosis. The best results were obtained, in most parameters studied, in groups of mice treated with silymarin in addition to PZQ.ConclusionsOur results point to silymarin as a promising anti-inflammatory and anti-fibrotic agent; it could be introduced as a therapeutic tool with PZQ in the treatment of schistosomal liver fibrosis, but further studies on mechanisms of silymarin and PZQ in chronic liver diseases may shed light on developing therapeutic methods in clinical practice.

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“…Fibrosis progression is not the sole determinant of subsequent decompensation or complications of portal hypertension. As such, it is also possible that silymarin does not have a beneficial effect on other determinants of clinical outcomes 32 . Alternatively, differences between histological progression and clinical outcomes could simply reflect chance.…”

Section: Discussionmentioning

confidence: 99%

Silymarin use and liver disease progression in the Hepatitis C Antiviral Long‐Term Treatment against Cirrhosis trial

Freedman¹,

Curto²,

Morishima³

et al. 2010

Aliment Pharmacol Ther

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Background Silymarin is the most commonly used herbal product for chronic liver disease, yet whether silymarin protects against liver disease progression remains unclear. Aim To assess the effects of silymarin use on subsequent liver disease progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had failed prior peginterferon plus ribavirin treatment. Methods Patients recorded their use of similymarin at baseline and were followed for liver disease progression (two point increase in Ishak fibrosis score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for clinical outcomes. Results At baseline, 34% of patients had ever taken silymarin, half of whom were current users. Use of silymarin was associated (p <0.05) with male sex; esophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among other features. Baseline users had less hepatic collagen content on study biopsies and had less histologic progression (HR: 0.57, 95%CI: 0.33–1.00; p-trend for longer duration of use=0.026). No effect was seen for clinical outcomes. Conclusion Silymarin use among patients with advanced hepatitis C-related liver disease is associated with reduced progression from fibrosis to cirrhosis, but has no impact on clinical outcomes. The HALT-C Trial was registered with Clinicaltrials.gov (#NCT00006164).

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Deleterious effects of silymarin on the expression of genes controlling endothelial nitric oxide synthase activity in carbon tetrachloride-treated rat livers

Cited by 14 publications

References 54 publications

The effects of Honey and Aloe Vera extract on Ibuprofen Induced Liver Damage in rats.

The effects of Honey and Aloe Vera extract on Ibuprofen Induced Liver Damage in rats.

Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis

Silymarin use and liver disease progression in the Hepatitis C Antiviral Long‐Term Treatment against Cirrhosis trial

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