Enhanced Arsenite-Induced Hepatic Morphological and Biochemical Changes in Phenobarbital-Pretreated Rats

Albores, Arnulfo; Cebrián, Mariano E.; Garcı́a-Vargas, Gonzalo G.; Connelly, John C.; Price, Shirley C.; Hinton, Richard H.; Bach, Peter H.; Bridges, James W.

doi:10.1177/019262339602400205

Cited by 11 publications

(5 citation statements)

References 28 publications

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“…We have also observed dilatation of the space between hepatic cords (Table 2) that is often related to observations of hepatocyte swelling, dilatation of sinusoidal capillaries, and bile canaliculi, which contribute to the alteration of the normal structure of the hepatic lobule and parenchyma disorganization (Albores et al, 1996;Flora et al, 2002). Some of the histological alterations observed in the present work may result from inflammation.…”

Section: Discussionsupporting

confidence: 85%

Protective Activity of Hesperidin and Lipoic Acid Against Sodium Arsenite Acute Toxicity in Mice

Neves

Carvalho

et al. 2004

Toxicol Pathol

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The objective of the present work was to evaluate the toxic effects of sodium arsenite, As(III), in mice and the protective effect of 2 antioxidants, hesperidin and lipoic acid, against the observed As(III)-induced toxicity. In each study, mice were assigned to 1 of 4 groups: control, antioxidant, antioxidant + arsenite, and arsenite. Animals were first injected with the vehicle or 25 mg antioxidant/kg BW. After 30 minutes they received an injection of 10 mg arsenite/kg BW or 0.9% NaCl. Two hours after the first injection, the liver, kidney, and testis were collected for histological evaluation. Liver samples were also taken for quantification of arsenic. In mice exposed only to As(III), various histopathological effects were observed in the liver, kidneys, and testes. In mice pretreated with either hesperidin or lipoic acid, a reduction of histopathologic effects on the liver and kidneys was observed. No protective effects were observed in the testes for either of the 2 studied antioxidants. In conclusion, hesperidin and lipoic acid provided protective effects against As(III)-induced acute toxicity in the liver and kidneys of mice. These compounds may potentially play an important role in the protection of populations chronically exposed to arsenic.

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Section: Discussionsupporting

confidence: 85%

Protective Activity of Hesperidin and Lipoic Acid Against Sodium Arsenite Acute Toxicity in Mice

Neves

Carvalho

et al. 2004

Toxicol Pathol

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“…For example, a significant decrease in hepatic glycogen content was reported in livers of mice and rats that were given a single or multiple doses of sodium arsenite or As 2 O 3 (3–15 mg/kg b.w.) orally or by injection (Reichl et al 1988; Verma et al 2004; Berry and Smythe 1959; Reichl et al 1991; Kawaguchi 1981; Albores et al 1996; Singh et al 2017; Huang et al 2015). Similarly, repeated injections of As 2 O 3 , 2.5 mg/kg b.w.…”

Section: Discussionmentioning

confidence: 99%

Exposures to arsenite and methylarsonite produce insulin resistance and impair insulin-dependent glycogen metabolism in hepatocytes

et al. 2017

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Environmental exposure to inorganic arsenic (iAs) has been shown to disturb glucose homeostasis, leading to diabetes. Previous laboratory studies have suggested several mechanisms that may underlie the diabetogenic effects of iAs exposure, including (i) inhibition of insulin signaling (leading to insulin resistance) in glucose metabolizing peripheral tissues, (ii) inhibition of insulin secretion by pancreatic β cells, and (iii) dysregulation of the methylation or expression of genes involved in maintenance of glucose or insulin metabolism and function. Published studies have also shown that acute or chronic iAs exposures may result in depletion of hepatic glycogen stores. However, effects of iAs on pathways and mechanisms that regulate glycogen metabolism in the liver have never been studied. The present study examined glycogen metabolism in primary murine hepatocytes exposed in vitro to arsenite (iAs) or its methylated metabolite, methylarsonite (MAs). The results show that 4-h exposures to iAs and MAs at concentrations as low as 0.5 and 0.2 µM, respectively, decreased glycogen content in insulin-stimulated hepatocytes by inhibiting insulin-dependent activation of glycogen synthase (GS) and by inducing activity of glycogen phosphorylase (GP). Further investigation revealed that both iAs and MAs inhibit insulin-dependent phosphorylation of protein kinase B/Akt, one of the mechanisms involved in the regulation of GS and GP by insulin. Thus, inhibition of insulin signaling (i.e., insulin resistance) is likely responsible for the dysregulation of glycogen metabolism in hepatocytes exposed to iAs and MAs. This study provides novel information about the mechanisms by which iAs exposure impairs glucose homeostasis, pointing to hepatic metabolism of glycogen as one of the targets.

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“…Several reports have revealed that the PAH and other cytochrome P450 inducers, such as phenobarbital, led the h e p a t o c e l l u l a r s E R p r o l i f e r a t i o n w i t h g l y c o g e n depletion 7,8,13 . However, there was no study that described the morphological alteration of hepatocellular glycogen granules before the proliferation of sER.…”

Section: Discussionmentioning

confidence: 99%

Initial Changes of Hepatic Glycogen Granules and Glycogen Phosphorylase <i>a</i> After Exposure to 7,12-dimethylbenz[<i>a</i>]anthracene in Rats

et al. 2003

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The initial changes in rat liver after a single oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) (100 mg/ kg b.w.) were examined ultrastructually. Glycogen granules of centrilobular hepatocytes increased with time to peak on Day 1. After this, they sharply decreased on Day 2, and on Days 5-10 returned to levels similar to those of the vehicle group (corn oil). On Day 2, the size of the centrilobular hepatocytes was decreased significantly, and the nuclear to cytoplasmic ratio was increased significantly. While the activity of hepatic glycogen phosphorylase a was decreased at 6-12 hrs and on Day 1, on Days 2-10, it was elevated to a level similar to that of the vehicle group. Thus, the initial temporary storage of hepatic glycogen granules following DMBA administration involved the inhibition of glycogenolysis in centrilobular hepatocytes. Glycogen granules appeared in restricted regions near the smooth endoplasmic reticulum (sER). Following DMBA administration, proliferation of sER of the centrilobular hepatocytes also gradually increased with time to peak on Day 2, after which it decreased, and on Days 5-10 returned to a level similar to that of the vehicle group. Results from the present study indicate that exposure of rats to DMBA could induce a reversible initial change in the hepatic glycogen metabolism. Moreover, the glycogen depletion of hepatocytes might be related to the high proliferation of sER that occurred concurrently on Day 2.

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Enhanced Arsenite-Induced Hepatic Morphological and Biochemical Changes in Phenobarbital-Pretreated Rats

Cited by 11 publications

References 28 publications

Protective Activity of Hesperidin and Lipoic Acid Against Sodium Arsenite Acute Toxicity in Mice

Protective Activity of Hesperidin and Lipoic Acid Against Sodium Arsenite Acute Toxicity in Mice

Exposures to arsenite and methylarsonite produce insulin resistance and impair insulin-dependent glycogen metabolism in hepatocytes

Initial Changes of Hepatic Glycogen Granules and Glycogen Phosphorylase <i>a</i> After Exposure to 7,12-dimethylbenz[<i>a</i>]anthracene in Rats

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