Pathological mechanisms in carbon tetrachloride hepatotoxicity

Brattin, William J.; Glende, Eric A.; Recknagel, Richard O.

doi:10.1016/0748-5514(85)90026-1

Cited by 371 publications

(240 citation statements)

References 79 publications

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“…Carbon tetrachloride (CCl 4 ) poisoning is one of the most commonly used models of acute liver damage. The hepatotoxic effects of CCl 4 were attributed to the excessive production of free radicals [2] . Previous studies have shown that natural compounds with antioxidant activity could ameliorate CCl 4 -induced liver damage, thus preventing acute liver failure [3,4] .…”

Section: Introductionmentioning

confidence: 99%

Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

et al. 2012

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Aim: To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl 4 -induced liver damage in mice. Methods: BALB/cN mice were intraperitoneally administered rutin (10, 50, and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl 4 in olive oil (2 mL/kg, 10% v/v). The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry. Results: Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl 4 -intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl 4 -intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl 4 -induced activation of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2). The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-β1 (TGF-β1) than rutin. Conclusion: Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and antiinflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.

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Section: Introductionmentioning

confidence: 99%

Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

et al. 2012

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“…CCl 4 administration can induce chronic liver damage in rats. It is metabolized by cytochrome P450 system to highly reactive trichloromethyl free radicals, which initiate liver cell destruction (McCay et al, 1984;Brattin et al, 1985). As previously reported, administration of CCl 4 for 8 weeks resulted in a significant increase in serum ALT, AST activities as well as total billirubin levels (Mehmetcik et al, 2008;Arici and Cetin, 2011).…”

Section: Discussionmentioning

confidence: 90%

Synergistic Effects of Jerusalem Artichoke in Combination with Pegylated Interferon Alfa-2a and Ribavirin Against Hepatic Fibrosis in Rats

Abdel-Hamid

Wahid²,

Nazmy³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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“…The hepatotoxicity of CCl 4 is very well studied and is believed to occur as a result of generation of free radicals within the liver [28]. The initial step in this hepatotoxicity is the production of the trichloromethyl radical (-•CCl 3 ) via the enzyme cytochrome P450 subtypes (2E1, 2B1, 2B2 and 3A) [29,30]. The latter radical then interacts with molecular oxygen resulting in the production of the trichloromethyl peroxyl radical (-•O-O-CCl 3 ) [30].…”

Section: Discussionmentioning

confidence: 99%

“…The initial step in this hepatotoxicity is the production of the trichloromethyl radical (-•CCl 3 ) via the enzyme cytochrome P450 subtypes (2E1, 2B1, 2B2 and 3A) [29,30]. The latter radical then interacts with molecular oxygen resulting in the production of the trichloromethyl peroxyl radical (-•O-O-CCl 3 ) [30]. This radical then initiates the peroxidation of the membrane phospholipids and the unsaturated fatty acids.…”

Section: Discussionmentioning

confidence: 99%

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Myrica rubra Fruit Drink Sub-Chronic Toxicity and Hepatoprotective Effect in Rats

Al-Hadiya¹

2013

Adv Pharmacoepidem Drug Safety

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Background: This study dealt with the effect of the subchronic toxicity of Myrica rubra fruit beverage drink (MRD) in rats and its hepatoprotective effect against carbon tetrachloride (CCl 4 )-induced hepatotoxicity.Methodology: Different groups of normal male and female Wistar rats were treated with 50% MRD as drinking vehicle (13 weeks), as substitution of the normal drinking water. Coulter Counter was used for red blood corpuscles (RBCs) and white blood corpuscles (WBCs) count. The Reflotron instrument and Reflotron haemoglobin kit used for determination of haemoglobin content, while the Reflotron strips for determination of blood glucose, total triglycerides and cholesterol contents, blood enzymatic levels, and bilirubin. Atomic absorption spectroscopy was used for determination of blood Na + , Mg ++ and Ca ++ concentrations.Principal findings: Treatment induced significant increases in the red blood corpuscles (RBCs) count, haematocrit and haemoglobin content. It also significantly decreased plasma levels of total cholesterol and the low-density lipoproteins (LDL) without affecting the levels of high-density lipoproteins (HDL), glucose, triglycerides and bilirubin, together with the significant decrease in hepatic malonaldehyde production. The treatment resulted in significant reductions in the enzymes alanine transiminase (ALT), aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) and a significant diuretic effect.

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Pathological mechanisms in carbon tetrachloride hepatotoxicity

Cited by 371 publications

References 79 publications

Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

Synergistic Effects of Jerusalem Artichoke in Combination with Pegylated Interferon Alfa-2a and Ribavirin Against Hepatic Fibrosis in Rats

Myrica rubra Fruit Drink Sub-Chronic Toxicity and Hepatoprotective Effect in Rats

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