Biphasic effect of colchicine on acute liver injury induced by carbon tetrachloride or by dimethylnitrosamine in mice

Mizuoka, Hiroshi; Shikata, Nobuaki; Yang, Jihong; Takasu, Masashi; Inoue, Katsumi; Tsubura, Airo

doi:10.1016/s0168-8278(99)80283-9

Cited by 15 publications

(11 citation statements)

References 26 publications

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“…In hepatotoxin-induced injury models, using Gal (90, 391), dimethylnitrosamine (565), acetaminophen (345,407), carbon tetrachloride (565), alcohol (30), microcystin-LR (153,894,896), and endotoxin (22), cytotoxicity has predominantly been related to apoptotic cell death, although necrotic tissue injury is also reported (227,560,909). The generation of reactive intermediate metabolites from the metabolism of hepatotoxins, and the generation of ROS during the inflammatory reaction account for the stimulation of a variety of pathways leading to cell death.…”

Section: B Apoptosis Oncotic Necrosis Secondary Necrosis and Aponmentioning

confidence: 99%

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

Vollmar

Menger²

2009

Physiological Reviews

426

368

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The complex functions of the liver in biosynthesis, metabolism, clearance, and host defense are tightly dependent on an adequate microcirculation. To guarantee hepatic homeostasis, this requires not only a sufficient nutritive perfusion and oxygen supply, but also a balanced vasomotor control and an appropriate cell-cell communication. Deteriorations of the hepatic homeostasis, as observed in ischemia/reperfusion, cold preservation and transplantation, septic organ failure, and hepatic resection-induced hyperperfusion, are associated with a high morbidity and mortality. During the last two decades, experimental studies have demonstrated that microcirculatory disorders are determinants for organ failure in these disease states. Disorders include 1) a dysregulation of the vasomotor control with a deterioration of the endothelin-nitric oxide balance, an arterial and sinusoidal constriction, and a shutdown of the microcirculation as well as 2) an overwhelming inflammatory response with microvascular leukocyte accumulation, platelet adherence, and Kupffer cell activation. Within the sequelae of events, proinflammatory mediators, such as reactive oxygen species and tumor necrosis factor-alpha, are the key players, causing the microvascular dysfunction and perfusion failure. This review covers the morphological and functional characterization of the hepatic microcirculation, the mechanistic contributions in surgical disease states, and the therapeutic targets to attenuate tissue injury and organ dysfunction. It also indicates future directions to translate the knowledge achieved from experimental studies into clinical practice. By this, the use of the recently introduced techniques to monitor the hepatic microcirculation in humans, such as near-infrared spectroscopy or orthogonal polarized spectral imaging, may allow an early initiation of treatment, which should benefit the final outcome of these critically ill patients.

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Section: B Apoptosis Oncotic Necrosis Secondary Necrosis and Aponmentioning

confidence: 99%

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

Vollmar

Menger²

2009

Physiological Reviews

426

368

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“…Carbon tetrachloride (CCl 4 ) is a well known hepatotoxin that is widely used to induce acutetoxic liver injury in a large range of laboratory animals (Rao et al, 1997;Mizuoka et al, 1999). Acute hepatotoxicity induces inflammation, necrosis, and oxidative stress of hepatocytes (Dong et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Morin protects acute liver damage by carbon tetrachloride (CCl4) in rat

et al. 2008

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The purpose of this study was to investigate possible beneficial effects of morin on CCl(4)-induced acute hepatotoxicity in rats. Rats received a single dose of CCl(4) (150 microL/100 g 1:1 in corn oil). Morin treatment (20 mg/kg) was given at 48, 24, and 2 h before CCl(4) administration. CCl(4) challenge elevated serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) levels, but these effects were prevented by the pretreatment of rats with morin. To identify the mechanism of protective activity of morin in CCl(4)-induced hepatotoxicity in rats, we investigated expressions of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and inducible nitric oxide (iNOS). The expressions of TNF-alpha, IL-1beta, IL-6, and iNOS were increased by CCl(4) treatment and increased expressions of those were decreased by morin. These findings suggest that morin prevents acute liver damage by inhibiting the production of TNF-alpha, IL-1beta, IL-6, and iNOS.

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“…A recent study performed by Mizuoka et al (30) with colchicine and CCl 4 showed a hepatoprotective effect when colchicine was administered 18 h before CCl 4 treatment, and an increase in hepatic injury when colchicine was administered 2 h before CCl 4 treatment. This hepatoprotective effect was related to the decreased hepatic content of cytochrome P450, and the acceleration of hepatic necrosis was ascribed to increased membrane lipid peroxidation (30). Another explanation for our observation may be an interference of CCl 4 with the half-life of PPS.…”

Section: Discussionmentioning

confidence: 93%

“…The increased hepatotoxicity of CCl 4 in association with PPS may have been due to other mechanisms, such as increased lipid peroxidation (28) and decreased concentrations of glutathione and alpha-tocopherol (29). A recent study performed by Mizuoka et al (30) with colchicine and CCl 4 showed a hepatoprotective effect when colchicine was administered 18 h before CCl 4 treatment, and an increase in hepatic injury when colchicine was administered 2 h before CCl 4 treatment. This hepatoprotective effect was related to the decreased hepatic content of cytochrome P450, and the acceleration of hepatic necrosis was ascribed to increased membrane lipid peroxidation (30).…”

Section: Discussionmentioning

confidence: 99%

Potentiation of carbon tetrachloride hepatotoxicity by pentosan polysulfate in rats

Zim

Silveira

Schwartsmann

et al. 2002

Braz J Med Biol Res

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Few data are available in the literature regarding the effect of pentosan polysulfate (PPS) on normal and fibrotic rat livers. In addition, the combination of PPS and carbon tetrachloride (CCl 4 ) has not been studied so far. The objective of this study was to assess the effect of PPS on rat livers treated or not with CCl 4 for the induction of liver fibrosis. The study consisted of four stages: 1) hepatic fibrosis induction with CCl 4 (N = 36 rats); 2) evaluation of the effect of PPS on CCl 4 -induced hepatic fibrosis (N = 36 rats); 3) evaluation of the effect of higher doses of PPS in combination with CCl 4 (N = 50 rats); 4) evaluation of the presence of an enzymatic inductor effect by PPS (N = 18 rats) using the sodium pentobarbital test which indirectly evaluates hepatic microsomal enzyme activity in vivo. Adult (60 to 70 days) male Wistar rats weighing 180 to 220 g were used. All animals receiving 0.5 ml 8% CCl 4 (N = 36) developed hepatic fibrosis, and after 8 weeks they also developed cirrhosis. No delay or prevention of hepatic fibrosis was observed with the administration of 5 mg/kg PPS (N = 8) and 1 mg/kg PPS (N = 8) 1 h after the administration of CCl 4 , but the increased hepatotoxicity resulting from the combination of the two substances caused massive hepatic necrosis in most rats (N = 45). PPS (40 mg/kg) alone caused hepatic congestion only after 8 weeks, but massive hepatic necrosis was again observed in association with 0.5 ml CCl 4 after 1 to 4 weeks of treatment. Unexpectedly, sleeping time increased with time of PPS administration (1, 2, or 3 weeks). This suggests that PPS does not function as an activator of the hepatic microsomal enzymatic system. Further studies are necessary in order to clarify the unexpected increase in hepatotoxicity caused by the combination of CCl 4 and high doses of PPS, which results in massive hepatic necrosis.

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Biphasic effect of colchicine on acute liver injury induced by carbon tetrachloride or by dimethylnitrosamine in mice

Cited by 15 publications

References 26 publications

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

Morin protects acute liver damage by carbon tetrachloride (CCl4) in rat

Potentiation of carbon tetrachloride hepatotoxicity by pentosan polysulfate in rats

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