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

Abstract

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.

Decreases in Binding Capacity of the Mitochondrial 18 kDa Translocator Protein Accompany Oxidative Stress and Pathological Signs in Rat Liver After DMBA Exposure

“…As determined with liver histopathology in the present study, the three DMBA treatments resulted in moderate toxic effects, comparable to cyclosporine-A-induced hepatotoxicity in rat liver (Rezzani et al 2005). As another parameter of liver histopathology, it has been reported that drug toxicity, including PAH, may be accompanied by glycogen overload owing to disturbed carbohydrate metabolism (Muto et al 2003;Pereira et al 2006;Singh et al 1997). Therefore, we also examined hepatocellular glycogen.…”

“…We paid special attention to the liver, since metabolic activation and detoxification of DMBA in vivo occur primarily in this organ (Moore et al 1986;Muto et al 2003). On the other hand, it is known that DMBA toxicity requires its conversion to 3,4-dyhydrodiol intermediates in the liver (Gao et al 2007;Miyata et al 2001).…”

“…This study served to determine potential correlations between DMBA exposure and oxidative stress in the liver, liver pathology, and TSPO binding characteristics in the liver. We paid special attention to the liver, since metabolic activation and detoxification of DMBA in vivo occur primarily in this organ (Moore et al 1986;Muto et al 2003). On the other hand, it is known that DMBA toxicity requires its conversion to 3,4-dyhydrodiol intermediates in the liver (Gao et al 2007;Miyata et al 2001).…”

Protective and Curative Effects of the Sea CucumberHolothuria atraExtract against DMBA-Induced Hepatorenal Diseases in Rats

“…This study served to determine potential correlations between DMBA exposure and oxidative stress in the liver, since metabolic activation and detoxification of DMBA in vivo occur primarily in this organ [ 51 , 52 ]. In conjunction with the reports of Parmar et al [ 53 ] and Parmar et al [ 54 ], data from the present investigation reflects that oxidative stress in the liver is a common feature of DMBA toxicity.…”

Time Course of Expression of 7,12-Dimethylbenz[a]anthracene-induced CYP1A1 and CYP1B1 mRNA and Protein in Rat Liver

“…Previously we observed the temporal depletion of rat hepatocyte glycogen granules with high proliferation of the smooth endoplasmic reticulum (sER) on day 2 following DMBA (100 mg/kg b.w.) administration, and suggested that the highest metabolism of DMBA might occur on day 2 8 , while the induction of CYP1mRNA was observed within 6 hr of DMBA administration 9 . However, no investigation concerning the time course of expression of liver CYP1 mRNA and proteins following DMBA administration has been reported.…”