Silymarin Effects on Intracellular Calcuim and Cytotoxicity: A Study in Perfused Rat Hepatocytes After Oxidative Stress Injury

Farghali, Hassan; Kameníková, L; Hynie, S.; Kmoníčková, Eva

doi:10.1006/phrs.1999.0575

Cited by 84 publications

(56 citation statements)

References 22 publications

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“…These are the oxygen reactive species implicated in the initiation and propagation of lipid peroxidation as well as in glutathione oxidation (Bellomo et al 1982;Fernandes et al 1995;Jewell et al 1986;Rush et al 1985). t-BHP-induced alkylation of cellular macromolecules or oxidation of thiol groups in cellular proteins has also been reported (Farghali et al 2000). These events are followed by formation of surface blebs in the plasma membrane as well as the leakage of cytosolic enzymes in the incubation medium.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective activity of polyhydroxylated 2-styrylchromones against tert-butylhydroperoxide induced toxicity in freshly isolated rat hepatocytes

Fernandes

Carvalho

et al. 2003

Arch Toxicol

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2-Styrylchromones are a novel class of chromones, vinylogues of flavones (2-phenylchromones), which have recently been found in nature. The best described property of almost every group of flavones and other flavonoids, especially the hydroxylated derivatives, is their capacity to act as antioxidants. Indeed there is a widely accepted view that the positive health effects of flavones are due to their antioxidant activity. As oxidative stress is a main cause of liver toxicity induced by several hepatotoxicants, agents with the ability to protect the liver against reactive pro-oxidant species may be therapeutically useful. The present study evaluated the possible protective activity of six new synthetic polyhydroxylated 2-styrylchromone derivatives against the pro-oxidant hepatotoxicity exerted by tert-butylhydroperoxide (t-BHP) in freshly isolated rat hepatocytes. The cells were preincubated with the 2-styrylchromones in the final concentrations of 3.125, 12.5, 25, 50, 100, and 200 lM for 5 min before treatment with 1.0 mM t-BHP for 30 min (throughout this incubation period the cells were exposed to both compounds). The well-known antioxidant 3-hydroxyflavone (quercetin) was used as positive control. At the end of the 30-min incubation period, aliquots of cells suspensions were taken for measurement of lactate dehydrogenase leakage, thiobarbituric acid reactive substances, reduced glutathione, and oxidized glutathione contents. The tested compounds exhibited in vitro protective activity against t-BHP induced hepatotoxicity (1.0 mM, 30 min). Three of the tested compounds, at the concentrations of 3.125, 12.5, 25, and 50 lM, prevented the t-BHP induced glutathione depletion, lipid peroxidation, and cell death in freshly isolated rat hepatocytes to a comparable potency with that of quercetin.

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Section: Discussionmentioning

confidence: 99%

Hepatoprotective activity of polyhydroxylated 2-styrylchromones against tert-butylhydroperoxide induced toxicity in freshly isolated rat hepatocytes

Fernandes

Carvalho

et al. 2003

Arch Toxicol

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“…In the present study, silymarin and two potent antioxidants, including vitamin E and curcumin, have been selected to evaluate their potential therapeutic effect against liver damaged induced by CCl4. Silymarin is a commonly used herbal therapy, particularly by patients who have liver disease, where it resulted in reducing serum bilirubin, and transaminases (Wellington and Jarvis 2001) This hepatoprotective effect of silymarin has been suggested to result from membrane-stabilizing, free radicals scavenging properties (Muriel and Mourelle 1990) inhibition of lipid peroxidation (Flora et al 1998) and modulation of hepatocyte Ca++ (Farghali et al 2000). Vitamin E is a natural component of the membrane lipid bilayer East and Balgaug 1991).…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Potential Role of Silymarin Alone or in Combination with Vitamin E and/ or Curcumin on the Carbon Tetrachloride Induced Liver Injury in Rat

Al-Rasheed

Faddah

Sharaf

et al. 2015

Braz. arch. biol. technol.

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The aim of this study was to investigate the effective role of silymarin either alone or in a combination with vitamin E and/or curcumin against the toxic impact of carbon tetrachloride (CCl4) induced liver injury The results revealed that administration of silymarin alone or in a combination with vitamin E and/or curcumin for 21 consecutive days, 24 h after CCl4 injection to rats, markedly ameliorated DNA damaged and apoptosis markers in rat livers, proinflammatory markers including tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP ) in rat livers as well as interleukin 6 (IL-6), interferon gamma (IFN-γ) and vascular endothelial growth factor (VEGF) in rat sera. These treatments also could ameliorated the alteration in cytochrome P450 2E1 (CYP2E1) activity in livers of CCl4 intoxicated rats as well as the increase in the serum alanine aminotransferase (ALT) compared with

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“…SIL stabilizes membranes, making cells more resistant to osmotic lysis and to the action of detergents. 23 SIL also prevents lipid peroxide formation in liver cells 24 due, at least in part, to its properties as a free radical scavenger. 25 In vitro, silibinin blocks proliferation of hepatic stellate cells, the main source of the excess of collagen in fibrosis.…”

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confidence: 99%

Beneficial effects of silymarin on estrogen-induced cholestasis in the rat: A study in vivo and in isolated hepatocyte couplets

Crocenzi

2001

Hepatology

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The effect of silymarin (SIL) on 17␣-ethynylestradiol (EE)-induced cholestasis was evaluated in rats. EE (5 mg/kg, subcutaneously, daily, for 5 days) decreased both the bilesalt-dependent and the bile-salt-independent fractions of the bile flow. The decrease in the former was associated to a reduction in the bile salt pool size (؊58%), and this effect was completely prevented by SIL. This compound also counteracted the inhibitory effect induced by EE on HCO 3 ؊ but not glutathione output, 2 major determinants of the bile-salt-independent bile flow. EE decreased the secretory rate maximum (SRM) of tauroursodeoxycholate, (؊71%) and bromosulfophthalein (BSP; ؊60%), as well as the expression of the BSP canalicular carrier, mrp2; SIL failed to increase mrp2 expression, and had only a marginal beneficial effect on both tauroursodeoxycholate and BSP SRM values. However, the two-compartment model-based kinetic constant for BSP canalicular transfer was significantly improved by SIL (؉262%). SIL decreased rather than increased CYP3A4, the cytochrome P450 isoenzyme involved in the oxidative metabolism of EE, and had no inhibitory effect on the UDP-glucuronosyltrasferase isoforms involved in the formation of its 17␤-glucuronidated, more cholestatic metabolite. Pretreatment of isolated rat hepatocyte couplets with silibinin, the major, active component of SIL, counter- Estrogens are well known to cause intrahepatic cholestasis in susceptible women during pregnancy, administration of oral contraceptives, and postmenopausal replacement therapy. 1 Given these clinical implications, experimental cholestasis induced by estrogen administration in rodents, mainly 17␣-ethynylestradiol (EE), has been widely used as an experimental model to assess the mechanisms involved in estrogeninduced cholestasis. These studies have shown that estrogens induce cholestasis by reducing both the bile-salt-dependent fraction of the bile flow (BSDF) and the bile-salt-independent fraction of the bile flow (BSIF). 1,2 The model in rats, however, requires estrogen dosages much greater than those required to induce cholestasis in susceptible women and fails to fully reproduce the pathology in humans in that little if any effect on serum parameters of hepatic damage, e.g., bile salt and bilirubin levels, is recorded. 3,4 The mechanism involved in the impairment of the BSDF is multifactorial. EE decreases sinusoidal uptake of bile acids, 5 at least in part by inducing down-regulation of the expression of the sodium-taurocholate cotransporting polypeptide protein, ntcp. 6 At the canalicular level, EE was shown to decrease the ATP-dependent taurocholate transport in hepatocyte canalicular membrane preparations, 5 which is thought to be due, at least in part, to an impairment in the expression of the canalicular bile salt export pump at a posttranscriptional level 7 ; this contributes to explain the decrease in the secretory rate maximum (SRM) of taurocholate, a parameter that is thought to evaluate the canalicular, rate-limiting transfer of bile salts in vivo...

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Silymarin Effects on Intracellular Calcuim and Cytotoxicity: A Study in Perfused Rat Hepatocytes After Oxidative Stress Injury

Cited by 84 publications

References 22 publications

Hepatoprotective activity of polyhydroxylated 2-styrylchromones against tert-butylhydroperoxide induced toxicity in freshly isolated rat hepatocytes

Hepatoprotective activity of polyhydroxylated 2-styrylchromones against tert-butylhydroperoxide induced toxicity in freshly isolated rat hepatocytes

Assessment of the Potential Role of Silymarin Alone or in Combination with Vitamin E and/ or Curcumin on the Carbon Tetrachloride Induced Liver Injury in Rat

Beneficial effects of silymarin on estrogen-induced cholestasis in the rat: A study in vivo and in isolated hepatocyte couplets

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