Carbon tetrachloride-induced hepatotoxicity in pregnant and lactating rats

Mochizuki, Masahiro; Shimizu, S.; Umeshita, Kazuhiko; Kamata, Takashi; Kitazawa, Takahiro; Nakamura, Daichi; Nishihata, Yoshito; Ohishi, Takumi; Edamoto, Hiroshi

doi:10.2131/jts.34.175

Cited by 17 publications

(15 citation statements)

References 25 publications

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“…CCl4 is metabolized in the liver by cytochrome P450 into the free radical CCl3 [36] . The free radical attacks hepatocytes and causes necrosis of parenchymal cells, which promotes inflammatory responses in the liver [37] .…”

Section: Discussionmentioning

confidence: 99%

Emodin protects rat liver from CCl₄-induced fibrogenesis via inhibition of hepatic stellate cells activation

Dong¹,

Yan²,

Zhang³

et al. 2009

WJG

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AIM: To investigate the role of emodin in protecting the liver against fibrogenesis caused by carbon tetrachloride (CCl4) in rats and to further explore the underlying mechanisms. METHODS:Rat models of experimental hepatic fibrosis were established by injection with CCl4; the treated rats received emodin via oral administration at a dosage of 20 mg/kg twice a week at the same time. Rats injected with olive oil served as a normal group. Histopathological changes were observed by hematoxylin and eosin staining. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and hepatic hydroxyproline content were assayed by biochemical analyses. The mRNA and protein relevant to hepatic stellate cell (HSC) activation in the liver were assessed using real-time reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, western blotting and enzymelinked immunosorbent assay. RESULTS:The degree of hepatic fibrosis increased markedly in the CCl4 group compared to the normal group (P < 0.01), and decreased markedly in the emodin group compared to the CCl4 group according to METAVIR scale (P < 0.01) compared with those in the normal control group (51.02 ± 10.64 IU/L and 132.28 ± 18.14 IU/L). The activities of serum ALT and AST were significantly higher in rats injected with CCl4 (289.25 ± 68.84 IU/L and 423.89 ± 35.67 IU/L, both P < 0.05).The activities of serum ALT and AST were significantly reduced by administration of emodin (176.34 ± 4 7. 2 9 I U / L a n d 2 2 6 . 1 ± 4 4. 5 2 I U / L , b o t h P < 0.05). Compared with the normal controls (54.53 ± 13.46 mg/g), hepatic hydroxyproline content was significantly higher in rats injected with CCl4 (120.27 ± 28.47 mg/g, P < 0.05). Hepatic hydroxyproline content was significantly reduced in the rats treated with emodin at 20 mg/kg (71.25 ± 17.02 mg/g, P < 0.05).Emodin significantly protected the liver from injury by reducing serum AST and ALT activities and reducing hepatic hydroxyproline content. The mRNA levels of transforming growth factor-β1 (TGF-β1), Smad4 and α-SMA in liver tissues were significantly down-regulated in SD rats that received emodin treatment. Furthermore, significant down-regulation of serum TGF-β1 protein levels and protein expression of Smad4 and α-SMA in liver tissues was also observed in the rats. Emodin inhibited HSC activation by reducing the abundance of TGF-β1 and Smad4. CONCLUSION:Emodin protects the rat liver from CCl4-induced fibrogenesis by inhibiting HSC activation. Emodin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis.

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Section: Discussionmentioning

confidence: 99%

Emodin protects rat liver from CCl₄-induced fibrogenesis via inhibition of hepatic stellate cells activation

Dong¹,

Yan²,

Zhang³

et al. 2009

WJG

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“…Carbon tetrachloride is said to induce hepatotoxicity in rats, rabbits and humans after being metabolised to trichloromethyl free radical which causes peroxidative degradation in the adipose tissue resulting in fatty infiltration of the hepatocytes [36,37,191]. Trichloromethyl free radicals elicit lipid peroxidation of membrane lipids in the presence of oxygen generated by metabolic leakage from mitochondria.…”

Section: Industrial Toxinsmentioning

confidence: 99%

Clinical Biochemistry of Hepatotoxicity

Sharma¹

2014

J Clinic Toxicol

103

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Liver plays a central role in the metabolism and excretion of xenobiotics which makes it highly susceptible to their adverse and toxic effects. Liver injury caused by various toxic chemicals or their reactive metabolites [hepatotoxicants) is known as hepatotoxicity. The present review describes the biotransformation of hepatotoxicants and various models used to study hepatotoxicity. It provides an overview of pathological and biochemical mechanism involved during hepatotoxicity together with alteration of clinical biochemistry during liver injury. The review has been supported by a list of important hepatotoxicants as well as common hepatoprotective herbs.

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“…These inflammatory changes are thought to be due to the action of CCl 4 . Mochizuki, et al (24) reported that CCl 4 is metabolized in the liver by cytochrome P450 into the free radical CCl 3 . The free radical attacks hepatocytes leads to lipid peroxidation and membrane damage, which results in a reversible acute centrilobular liver necrosis, which promotes inflammatory responses in the liver.…”

Section: Discussionmentioning

confidence: 99%

Effect of Exogenous Interleukin-10 on Carbon Tetrachloride CCL4-Induced Hepatic Fibrosis in Rats

El-Din¹,

Hassan²,

Abdel-Hamed³

et al. 2013

Suez Canal University Medical Journal

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Background: Transforming growth factor β1 (TGF-β1) is one of the strongest profibrotic cytokines and TGF-β1/Smad signaling is the cardinal signal transduction pathway involved in fibrosis. Previous studies indicated that exogenous IL-10 down regulates collagen type I. It also exerts antifibrogenic effect by down regulating profibrogenic cytokines such as (TGF-β1). All these studies indicate that IL-10 might become a new therapeutic target. Aim: To investigate the potential therapeutic effect of exogenous interleukin-10 on reversing the well-established hepatic fibrosis of CCl 4 administration in experimental rats. Materials and Methods: Albino rats were divided into four groups (27 rats each): group A (control), group B1 (CCl 4-treated), group B2 (spontaneous recovery, SR) and group B3 (IL-10-treated). Rats' liver tissue was stained with i) hematoxylin and eosin (H & E) and, ii) Masson's trichrome stains for evaluation of the histological activity index (HAI). Serum TGF-β1 was determined by ELISA. Results: No inflammation was found in the control group, however, marked inflammation (grade 3) was observed in CCl 4-induced fibrosis group while moderate inflammation (grade 2) was observed in SR group. Meanwhile the administration of IL-10 in group D resulted in a marked decrease in the grading of inflammation (grade 1) compared to CCl 4-induced fibrosis group. No fibrosis was observed in the control group, however, a marked fibrosis reaching to cirrhosis (stages 3&4) was observed in CCl 4-induced fibrosis group. The degree of fibrosis showed a mild decrease (stage 3) in SR group. Meanwhile the administration of IL-10 in group D resulted in a marked decrease in the stage of fibrosis to (stage 1). Serum TGF-β1 concentration dramatically increased in CCl 4-induced fibrosis group compared to the control group. It also increased in SR group, but lesser than CCl 4 treated group while it was significantly reduced in the IL-10 treated group. Conclusions: Our results provide evidence towards the potential effect of IL-10 as anti-TGF-β1 that could lead to a reduction of hepatic fibrosis.

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Carbon tetrachloride-induced hepatotoxicity in pregnant and lactating rats

Cited by 17 publications

References 25 publications

Emodin protects rat liver from CCl₄-induced fibrogenesis via inhibition of hepatic stellate cells activation

Emodin protects rat liver from CCl₄-induced fibrogenesis via inhibition of hepatic stellate cells activation

Clinical Biochemistry of Hepatotoxicity

Effect of Exogenous Interleukin-10 on Carbon Tetrachloride CCL4-Induced Hepatic Fibrosis in Rats

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Carbon tetrachloride-induced hepatotoxicity in pregnant and lactating rats

Cited by 17 publications

References 25 publications

Emodin protects rat liver from CCl4-induced fibrogenesis via inhibition of hepatic stellate cells activation

Emodin protects rat liver from CCl4-induced fibrogenesis via inhibition of hepatic stellate cells activation

Clinical Biochemistry of Hepatotoxicity

Effect of Exogenous Interleukin-10 on Carbon Tetrachloride CCL4-Induced Hepatic Fibrosis in Rats

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Emodin protects rat liver from CCl₄-induced fibrogenesis via inhibition of hepatic stellate cells activation

Emodin protects rat liver from CCl₄-induced fibrogenesis via inhibition of hepatic stellate cells activation