Liver regeneration after carbon tetrachloride intoxication in the rat

Nakata, Rieko; Tsukamoto, Ikuyo; Miyoshi, Masamitsu; Kojo, Shosuke

doi:10.1016/0006-2952(85)90195-9

Cited by 59 publications

(26 citation statements)

References 15 publications

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“…The time course of LR differs regarding the inducting agent 32 ; labeling nuclear index is maximal 18 to 36 hours after PH with a peak at 24 hours and 18 to 72 hours after treatment with CCl 4 (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

Changes in mitochondrial adenine nucleotides and in permeability transition in two models of rat liver regeneration

et al. 2003

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Although enhanced phosphorylative activity can be a requisite for later DNA synthesis during liver regeneration (LR), mitochondrial generation of reactive oxygen species could lead to altered mitochondrial membrane permeability during the prereplicative phase of LR. Therefore, the role of mitochondrial permeability transition (MPT) was evaluated during rat LR, induced by either partial hepatectomy (PH) or after CCl 4 administration. Parameters indicative of mitochondrial function and membrane potentials, those of oxidative stress, and in vivo changes of the intramitochondrial pool of adenine nucleotides were determined. Twelve hours after PH, mitochondrial oxidative and phosphorylative activities and adenosine diphosphate (ADP) content were increased, reaching a maximal peak at 24 hours after surgery (maximal DNA synthesis). Parameters suggestive of oxidant stress were enhanced, but mitochondrial volume and membrane electrical potential remained unaltered. Interestingly, moderate mitochondrial swelling and depolarization were found at later post-PH times (72 hours). In CCl 4 -treated animals, it was found that an active liver cell necrosis delayed mitotic activity and mitochondrial uncoupled respiration. Starting 12 hours after CCl 4 intoxication, a drastic increase of inorganic phosphate occurred within swollen and strongly depolarized mitochondria, suggesting changes in the MPT. Despite expression of messenger RNA (mRNA) for mitochondrial transcription, factor A showed a similar time course in both experimental models. The so-called augmenter liver regeneration was found significantly elevated only in PH rats. In conclusion, onset of MPT could be associated with cell necrosis and inflammation after CCl 4 treatment, whereas this mitochondrial event could constitute a putative effector mechanism, through which growth or inflammatory factors inhibiting cell proliferation could initiate LR termination. (HEPATOLOGY 2003;37:842-851.)

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Section: Discussionmentioning

confidence: 99%

Changes in mitochondrial adenine nucleotides and in permeability transition in two models of rat liver regeneration

et al. 2003

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“…For example, potentiation of CCl, hepatotoxicity by chlordecone (CD) has been observed as early as 4 hr and the rats die starting at 36 hr after administration (1,23,29), at which time the induction of liver regeneration has been reported (25,31,43). These studies also revealed novel information pertaining to hepatocellular regeneration.…”

Section: Introductionmentioning

confidence: 99%

Protection of Hepatotoxic and Lethal Effects of CCl by Partial Hepatectomy

et al. 1989

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CCI, is a hepatotoxic haloalkane, capable of producing hepatocellular fatty degenention and centrilobular necrosis. Previous reports indicate induction of liver regeneration after 3 6 4 8 hr of CCI, treatment, which is considered as a secondary effect. The present investigation was undertaken to evaluate the primary effects of CCI, on hepatic DNA synthesis and to correlate liver regeneration with CCI, toxicity. These studies were conducted in normal and actively regenerating livers using male Spngue-Dawley rats undergoing sham operation (SH), or partial (70%) hepatectomy (PH). Incorporation of 'H-thymidine ('H-T) in hepatocellular nuclear DNA and autoradiographic analyses of liver sections served as indices for hepatocellular regeneration. Initial experiments established that peak regeneration occurs at 2 days post-PH (PH,) and liver regeneration phases out by 7 days post-PH (PH,). SH and PH rats were challenged with a single ip dose of either corn oil vehicle or CCI, at either 0.1 mVkg (to represent subtoxic dose) or 2.5 mVkg (to represent toxic dose). The low dose of CCI, was not toxic and did not alter 'H-T incorporation and percentage labelled cells at 6 or 24 hours after administration to SH, PH, or PH, groups, indicating that there was no interference with PHstimulated hepatocellular regeneration. The high dose of CCI, was significantly hepatotoxic and lethal in SH rats, while in PH, rats both hepatotoxic and lethal effects were significantly decreased. 'H-T incorporation as well as percentage labelled cells, highly stimulated by PH, were significantly decreased by high dose of CCI,. However, hepatocellular regeneration in PH2 rats treated with high dose of CCI, was still significantly higher than SH or PH, groups by virtue of the stronger stimulatory effect of PH. In PH, nts, where hepatocellular regeneration had returned to the SH level, the hepatotoxic and lethal effects of the large dose of CCI, were also restored. These findings show that the progressive phase of a single high dose of CCI, injury which normally culminates in hepatotoxic and lethal eKects is significantly mitigated by previously stimulated hepatocellular regeneration. High dose of CCI, suppresses hepatocellular regeneration at early time points after administration in contrast to the smaller subtoxicdose ofCCI,. By virtue ofthe much stronger stimulatory effect, PH results in the protection against the hepatotoxic and lethal effects of CCI, despite the obtunding effects of the high dose on hepatocellular regeneration.

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“…12) Along with extensive cell death maximally occurring 24-48 h after CCl 4 administration, processes for survival and regeneration of the liver cells occur simultaneously. 13,14) Furthermore, these cytokines also contribute to the regeneration process. 15) Although the involvement of Kupffer cells in the liver cell death caused by CCl 4 has been evaluated utilizing gadolinium chloride (GdCl 3 ), 9) assumed to be a specific inhibitor of Kupffer cells, recent studies have indicated that GdCl 3 exerts hepatoprotective effects other than depleting Kupffer cells.…”

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The Role of Kupffer Cells in Carbon Tetrachloride Intoxication in Mice

Kiso

Ueno

Fukuda

et al. 2012

Biological & Pharmaceutical Bulletin

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Carbon tetrachloride (CCl 4 )-induced acute hepatitis is assumed to involve two phases. The initial phase, initiated within 2 h after CCl 4 administration, involves the generation of reactive oxygen species. The second phase is assumed to start about 8 h subsequent to CCl 4 administration and involves the oxidant-induced activation of Kupffer cells, which release various pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We investigated the role of Kupffer cells during CCl 4 intoxication using Nucling-knockout mice (the KO group), in which the number of Kupffer cells is largely reduced. Plasma alanine transaminase and aspartate transaminase levels demonstrated that the liver necrosis during the second phase was significantly alleviated in the KO group compared with that in the wild-type mice (the WT group). Plasma TNF-α concentrations in the WT group significantly increased 24 h after CCl 4 intoxication, whereas those in the KO group did not significantly increase. Plasma IL-6 levels also significantly increased in the WT group 24 h after CCl 4 administration, but those in the KO group did not increase at any time point. These results indicated that excess reactions of Kupffer cells, once primed by oxidants, were involved in the exacerbation of oxidative stress and liver damage during the second phase of CCl 4 intoxication.

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Liver regeneration after carbon tetrachloride intoxication in the rat

Cited by 59 publications

References 15 publications

Changes in mitochondrial adenine nucleotides and in permeability transition in two models of rat liver regeneration

Changes in mitochondrial adenine nucleotides and in permeability transition in two models of rat liver regeneration

Protection of Hepatotoxic and Lethal Effects of CCl by Partial Hepatectomy

The Role of Kupffer Cells in Carbon Tetrachloride Intoxication in Mice

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