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Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice.

Sukkasem N, Chatuphonprasert W, Tatiya-Aphiradee N, Jarukamjorn K - J Intercult Ethnopharmacol (2016)

Bottom Line: Plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, hepatic lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and the ratio of reduced to oxidized glutathione (GSH/GSSG) were determined.Plumbagin and PI significantly increased plasma ALT and AST levels, hepatic lipid peroxidation, and GPx activity but significantly decreased hepatic SOD and CAT activities.The GSH/GSSG ratio was significantly reduced by plumbagin.

View Article: PubMed Central - PubMed

Affiliation: Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology, Khon Kaen University.

ABSTRACT

Background/aim: Plumbago indica (PI) L. and its active constituent, plumbagin, has been traditionally claimed for several pharmacological activities; however, there is little information regarding their toxicity. The present study aims to examine the effects of plumbagin and PI extract (PI) on hepatic histomorphology and antioxidative system in mice.

Materials and methods: Adult male intelligent character recognition mice were intragastrically administered plumbagin (1, 5, and 15 mg/kg/day) or PI (20, 200, and 1,000 mg/kg/day) consecutively for 14 days. Hepatic histomorphology was examined. Plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, hepatic lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and the ratio of reduced to oxidized glutathione (GSH/GSSG) were determined.

Results: Plumbagin and PI concentration-dependently induced hepatic injury based on histopathological changes via imbalance of antioxidative system. Plumbagin and PI significantly increased plasma ALT and AST levels, hepatic lipid peroxidation, and GPx activity but significantly decreased hepatic SOD and CAT activities. The GSH/GSSG ratio was significantly reduced by plumbagin.

Conclusion: Plumbagin and PI caused hepatotoxic effects in the mice by unbalancing of the redox defense system. Therefore, plumbagin and PI-containing supplements should be used cautiously, especially when consumed in high quantities or for long periods.

No MeSH data available.


Related in: MedlinePlus

Liver histomorphology. Hepatic histomorphology of the mice treated with (a) control, 0.5% carboxymethyl cellulose (CMC), i.g., for 14 days, (b-d) Plumbagin in 0.5% CMC at the doses of 1, 5, and 15 mg/kg/day, i.g., for 14 days, (e-g) P. indica extract in 0.5% CMC at the doses of 20, 200, and 1,000 mg/kg/day, i.g., for 14 days. BD: Bile duct; PV: Portal vein. Open arrows indicate nuclear shrinkage. Closed arrows and circles indicate hydropic cell swelling
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Figure 2: Liver histomorphology. Hepatic histomorphology of the mice treated with (a) control, 0.5% carboxymethyl cellulose (CMC), i.g., for 14 days, (b-d) Plumbagin in 0.5% CMC at the doses of 1, 5, and 15 mg/kg/day, i.g., for 14 days, (e-g) P. indica extract in 0.5% CMC at the doses of 20, 200, and 1,000 mg/kg/day, i.g., for 14 days. BD: Bile duct; PV: Portal vein. Open arrows indicate nuclear shrinkage. Closed arrows and circles indicate hydropic cell swelling

Mentions: The histomorphological findings of the H&E-stained livers were shown in Figure 2. The control group demonstrated normal hepatic histomorphology [Figure 2a]. Mice fed with the lowest dose of plumbagin (1 mg/kg/day) [Figure 2b] and the PI extract (20 mg/kg/day) [Figure 2e] were not found any change in hepatic histomorphological anatomy compared to the control group. However, at the higher doses of both plumbagin and the PI extract, the evidence of liver injury was observed. The livers of mice received plumbagin (5 and 15 mg/kg/day) [Figure 2c and d] and the PI extract (200 and 1,000 mg/kg/day) [Figure 2f and g] were presented the nuclear shrinkage, where the nuclear chromatin materials were condensed and clumped together. In addition, at the highest doses of plumbagin (15 mg/kg/day) [Figure 2d] and the PI extract (1,000 mg/kg/day) [Figure 2g], the hepatic hydropic cell swelling, where the cytoplasm of hepatocyte was filled with vacuoles, and nuclear fading along with some hepatocyte nuclei disappearance were extensively observed. These hepatic histopathological findings revealed that plumbagin and the PI extract induced hepatotoxicity in the dose-dependent pattern.


Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice.

Sukkasem N, Chatuphonprasert W, Tatiya-Aphiradee N, Jarukamjorn K - J Intercult Ethnopharmacol (2016)

Liver histomorphology. Hepatic histomorphology of the mice treated with (a) control, 0.5% carboxymethyl cellulose (CMC), i.g., for 14 days, (b-d) Plumbagin in 0.5% CMC at the doses of 1, 5, and 15 mg/kg/day, i.g., for 14 days, (e-g) P. indica extract in 0.5% CMC at the doses of 20, 200, and 1,000 mg/kg/day, i.g., for 14 days. BD: Bile duct; PV: Portal vein. Open arrows indicate nuclear shrinkage. Closed arrows and circles indicate hydropic cell swelling
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835988&req=5

Figure 2: Liver histomorphology. Hepatic histomorphology of the mice treated with (a) control, 0.5% carboxymethyl cellulose (CMC), i.g., for 14 days, (b-d) Plumbagin in 0.5% CMC at the doses of 1, 5, and 15 mg/kg/day, i.g., for 14 days, (e-g) P. indica extract in 0.5% CMC at the doses of 20, 200, and 1,000 mg/kg/day, i.g., for 14 days. BD: Bile duct; PV: Portal vein. Open arrows indicate nuclear shrinkage. Closed arrows and circles indicate hydropic cell swelling
Mentions: The histomorphological findings of the H&E-stained livers were shown in Figure 2. The control group demonstrated normal hepatic histomorphology [Figure 2a]. Mice fed with the lowest dose of plumbagin (1 mg/kg/day) [Figure 2b] and the PI extract (20 mg/kg/day) [Figure 2e] were not found any change in hepatic histomorphological anatomy compared to the control group. However, at the higher doses of both plumbagin and the PI extract, the evidence of liver injury was observed. The livers of mice received plumbagin (5 and 15 mg/kg/day) [Figure 2c and d] and the PI extract (200 and 1,000 mg/kg/day) [Figure 2f and g] were presented the nuclear shrinkage, where the nuclear chromatin materials were condensed and clumped together. In addition, at the highest doses of plumbagin (15 mg/kg/day) [Figure 2d] and the PI extract (1,000 mg/kg/day) [Figure 2g], the hepatic hydropic cell swelling, where the cytoplasm of hepatocyte was filled with vacuoles, and nuclear fading along with some hepatocyte nuclei disappearance were extensively observed. These hepatic histopathological findings revealed that plumbagin and the PI extract induced hepatotoxicity in the dose-dependent pattern.

Bottom Line: Plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, hepatic lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and the ratio of reduced to oxidized glutathione (GSH/GSSG) were determined.Plumbagin and PI significantly increased plasma ALT and AST levels, hepatic lipid peroxidation, and GPx activity but significantly decreased hepatic SOD and CAT activities.The GSH/GSSG ratio was significantly reduced by plumbagin.

View Article: PubMed Central - PubMed

Affiliation: Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology, Khon Kaen University.

ABSTRACT

Background/aim: Plumbago indica (PI) L. and its active constituent, plumbagin, has been traditionally claimed for several pharmacological activities; however, there is little information regarding their toxicity. The present study aims to examine the effects of plumbagin and PI extract (PI) on hepatic histomorphology and antioxidative system in mice.

Materials and methods: Adult male intelligent character recognition mice were intragastrically administered plumbagin (1, 5, and 15 mg/kg/day) or PI (20, 200, and 1,000 mg/kg/day) consecutively for 14 days. Hepatic histomorphology was examined. Plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, hepatic lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and the ratio of reduced to oxidized glutathione (GSH/GSSG) were determined.

Results: Plumbagin and PI concentration-dependently induced hepatic injury based on histopathological changes via imbalance of antioxidative system. Plumbagin and PI significantly increased plasma ALT and AST levels, hepatic lipid peroxidation, and GPx activity but significantly decreased hepatic SOD and CAT activities. The GSH/GSSG ratio was significantly reduced by plumbagin.

Conclusion: Plumbagin and PI caused hepatotoxic effects in the mice by unbalancing of the redox defense system. Therefore, plumbagin and PI-containing supplements should be used cautiously, especially when consumed in high quantities or for long periods.

No MeSH data available.


Related in: MedlinePlus