The Protective Effects of Curcuma longa Linn. Extract on Carbon Tetrachloride-Induced Hepatotoxicity in Rats via Upregulation of Nrf2 (original) (raw)
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Toxicology, 2001
Glutathione S-transferases and glutathione play an important role in the detoxification of most toxic agents. In the present study, the protective effects of some antioxidants (L-ascorbic acid (AA), vitamin E (VE) or garlic) on carbon tetrachloride-induced changes in the activity of alanine amino transferase (ALT), aspartate amino transferase (AST), glutathione S-transferase (GST), and the level of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were studied. The activities of ALT, and AST were assayed in plasma, whereas the activity of GST and the levels of GSH and TBARS were determined in the livers of rats. The current study included two experiments. In the first experiment, animals received single oral dose of CCl 4 (400 mg/kg body weight) after administration of AA (100 mg/kg b.w.), VE (100 mg/kg b.w.) or garlic (800 mg/kg b.w.) as single oral doses. In the second experiment, rats received repeated oral doses of antioxidants for 12 consecutive days followed by a single oral dose of CCl 4 on the 13th day and killed after that by 24 h. Treatment of male rats with CCl 4 significantly increased the activity of ALT and AST in plasma, and the levels of both GSH and TBARS in the liver. On the other hand, CCl 4 inhibited the activity of GST after single dose treatment. Single-dose treatments of rats with AA, VE or garlic prior to the administration of CCl 4 could not restore the alterations in the activity of ALT and AST caused by CCl 4 to the normal control level. However, repeated dose treatments with these agents restored such alterations to the normal level. We observed that VE is more effective than AA and garlic in restoring the inhibition of GST activity caused by CCl 4 to the normal level after single dose treatments. On the other hand, AA and VE are more effective than garlic in restoring the induced TBARS level caused by CCl 4 to the normal control level after repeated dose treatments. It has been observed that the tested antioxidants were able to antagonize the toxic effects of CCl 4 , and such counteracting effects were more pronounced when they were administered as repeated doses prior to administration of CCl 4 .
Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat
BMC Complementary and Alternative Medicine, 2011
Background: Carissa opaca (Apocynaceae) leaves possess antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative in hepatic disorders. The effect produced by methanolic extract of Carissa opaca leaves (MCL) was investigated on CCl 4-induced liver damages in rat. Methods: 30 rats were divided into five groups of six animals of each, having free access to food and water ad libitum. Group I (control) was given olive oil and DMSO, while group II, III and IV were injected intraperitoneally with CCl 4 (0.5 ml/kg) as a 20% (v/v) solution in olive oil twice a week for 8 weeks. Animals of group II received only CCl 4. Rats of group III were given MCL intragastrically at a dose of 200 mg/kg bw while that of group IV received silymarin at a dose of 50 mg/kg bw twice a week for 8 weeks. However, animals of group V received MCL only at a dose of 200 mg/kg bw twice a week for 8 weeks. The activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and γ-glutamyltransferase (γ-GT) were determined in serum. Catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), glutathione reductase (GSR) and quinone reductase (QR) activity was measured in liver homogenates. Lipid peroxidation (thiobarbituric acid reactive substances; TBARS), glutathione (GSH) and hydrogen peroxide (H 2 O 2) concentration was also assessed in liver homogenates. Phytochemicals in MCL were determined through qualitative and high performance liquid chromatography (HPLC) analysis. Results: Hepatotoxicity induced with CCl 4 was evidenced by significant increase in lipid peroxidation (TBARS) and H 2 O 2 level, serum activities of AST, ALT, ALP, LDH and γ-GT. Level of GSH determined in liver was significantly reduced, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GSR, GST and QR. On cirrhotic animals treated with CCl 4 , histological studies showed centrilobular necrosis and infiltration of lymphocytes. MCL (200 mg/kg bw) and silymarin (50 mg/kg bw) co-treatment prevented all the changes observed with CCl 4-treated rats. The phytochemical analysis of MCL indicated the presence of flavonoids, tannins, alkaloids, phlobatannins, terpenoids, coumarins, anthraquinones, and cardiac glycosides. Isoquercetin, hyperoside, vitexin, myricetin and kaempherol was determined in MCL. Conclusion: These results indicate that MCL has a significant protective effect against CCl 4 induced hepatotoxicity in rat, which may be due to its antioxidant and membrane stabilizing properties.
Environmental Health and Preventive Medicine
Background: This study aims to assess the hepatoprotective potential of Commelina nudiflora against CCl 4-induced hepatic injury in rats. Method: Antioxidant activities were determined. Phytochemical analysis was performed by gas chromatography mass spectrometry (GCMS). In the in vivo study, Sprague Dawley rats were pretreated with C. nudiflora (150, 300, and 450 mg kg body weight (b.wt.)) once daily for 14 days followed by two doses of CCl 4 (1 ml/kg b.wt.). After 2 weeks, the rats were sacrificed and hepatoprotective analysis was performed. Results: In vitro studies have shown that the extract possessed strong antioxidant activity and has ability to scavenge 2,2-diphenyl-2-picrylhydrazyl-free radicals effectively. GCMS analysis of the C. nudiflora extract revealed the presence of various bioactive compounds. Administration of C. nudiflora significantly reduced the impact of CCl 4 toxicity on serum markers of liver damage, serum aspartate transaminase (AST), and alanine transaminase (ALT). C. nudiflora also increased antioxidant levels of hepatic glutathione (GSH) and antioxidant enzymes and ameliorated the elevated hepatic formation of malondialdehyde (MDA) induced by CCl 4 in rats. Histopathological examination indicated that C. nudiflora protect the liver from the toxic effect of CCl 4 and healed lesions such as necrosis, fatty degeneration, and hepatocyte injury as irregular lamellar organization and dilations in the endoplasmic reticulum. The immunohistochemical studies revealed that pretreatment of C. nudiflora decreased the formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Furthermore, overexpression of the proinflammatory cytokines TNF-α, IL-6, and prostaglandin E2 is also reduced. Conclusion: These findings exhibited the potential prospect of C. nudiflora as functional ingredients to prevent ROS-related liver damage.
Antioxidants as effective remedies at hepatotoxic action of carbon tetrachloride
Journal of Biophysical Chemistry, 2014
The liver, as the central metabolic organ, plays an important role in metabolism of carbohydrates, lipids and proteins. In the environment, there are many hepatotoxic xenobiotics. CCl4 is a free radical toxic for organelles of hepatocytes. The presented work was studying the character of ultrastructural changes in CCl4-intoxicated hepatocytes as well as the tissue after treatment by grape seed extract (GSE), α-tocopherol (α-T). As a result of cell bioremediation effect and reactions against corruptive factors, the liver has a high regeneration ability.
Journal of Drug Delivery and Therapeutics
Objective: The present study aims to study the effect of thymoquinone as prophylactic treatment against CCl4-induced hepatotoxicity on antioxidants status. Methodology: Hepatotoxicity was induced in rats by intraperitoneal administration of 3 ml/kg, 1:1 (V/V) mixture of CCl4 and olive oil after treatment for 7 days with TQ, using two doses. The method consists of studying the antioxidant effect of thymoquinone pretreatment by measuring superoxide dismutase (SOD) and catalase (CAT) activities, with reduced glutathione level in both plasma and liver homogenate. Results: The results revealed that hepatotoxicity is accompanied by significant decrease (p ≤ 0.01) of SOD and CAT activities with GSH level, in both plasma and liver homogenate. While prophylactic treatment using TQ at doses of 02.5 and 05 mg/kg increase significantly the status of the antioxidants, as dose dependent manner, in both plasma and liver homogenate. Conclusion: The results of this study show that thymoquinone has ...
Comunicata Scientiae, 2012
The current study was undertaken to evaluate the hepatoprotective potential of aged garlic extract (AGE) against hepatotoxicity induced by CCl 4 in adult male rats. CCl 4 intoxication (1ml/ kg b.w., twice a week, i.p. for 4 weeks) significantly increased oxidative stress as indicated by increased hepatic MDA formation, decreased both serum total and reduced glutathione contents, and inhibition of hepatic glutathione reductase and serum paraoxonase 1(POX1) activities. In addition, treatment with CCl 4 produced a significant increase in the activities of serum ALT, AST and albumin level with a significant decrease in total protein level. Moreover, treatment with CCl 4 resulted in significant increase in the levels of total cholesterol, LDL-cholesterol, triglycerides as well as creatine kinase isoenzyme and lactate dehydrogenase activities, and a significant decrease in HDL-cholesterol compared to control group. Oral treatment with AGE at doses of 100 and 200 mg/ kg/day in combination with CCl 4 significantly ameliorated the severity of CCl 4-induced changes in the above mentioned parameters in a dose-dependent manner. In conclusion, the present study indicated that AGE improves POX1 activity and attenuates liver and cardiac dysfunction induced by CCl 4. The protective effects of AGE against CCl 4 toxicity may be attributed to its antioxidant and free radical scavenging activities due to its higher contents of organosulphur compounds.
A single acute hepatotoxic dose of CCl 4 causes oxidative stress in the rat brain
Toxicology Reports, 2015
Carbon tetrachloride (CCl 4), a hepatotoxic agent is widely used to study the toxic mechanisms in experimental animals. We have investigated whether oxidative stress is induced in the brain at a single hepatotoxic dosage (1 ml/kg bw) of CCl 4. Increased lipid peroxidation (LPO), protein carbonyls (PC) content and glutathione (GSH) depletion were observed in the brain regions of rats treated with CCl 4 which was higher than that of liver. A drastic reduction in the activity of glutathione-S-transferase (GST) was seen in the brain regions which was higher than that of liver. Similarly, activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), NADH-and NADPHdehydrogenase were reduced in the brain regions similar to that of liver. Higher induction of oxidative stress in the brain compared to that of liver implies vulnerability of the brain for CCl 4 neurotoxicity. Our study shows that a single hepatotoxic dose of CCl 4 is equally neurotoxic to rats.
2014
Effects of n-butanol fraction of Gongronema latifolium leave extract on some liver function and histological parameters in CCl 4-induced oxidative damage in Wistar albino rats were assessed. Fifty-four (54) Wistar albino rats were divided into treatment group and LD 50 groups. Group A (normal control) was given feed and water, Group B (vehicle control) was injected with olive oil intraperitoneally, while the rest groups (C, D, E, F and G) were injected intraperitoneally with a single dose of CCl 4 (148 mg/kg) as a 1:1 (v/v) solution in olive oil and all the animals were fasted for 36 hours. This was repeated once every week for a period of four (4) weeks. At the end of 28 days of treatment, liver marker enzymes studies showed that there was significant (p<0.05) increase in the serum activities of ALT, AST, ALP and bilirubin concentrations in CCl 4-induced control group when compared with the normal control and induced treated groups but there was no significant (p>0.05) difference of these liver marker enzymes and bilirubin levels between the normal control and induced treated groups. Antioxidant assay on the liver homogenate showed that there was significant (p<0.05) decrease in SOD, CAT, GPx and a significant increase (p<0.05) in MDA of CCl 4-induced control rats when compared to the normal control rats but there was no significant (p>0.05) difference between the normal control and induced treated groups. These findings suggested that n-butanol fraction of methanolic leave extract of G. latifolium may have anti-hepatotoxic and antioxidative effects against CCl 4-induced liver damage in rats.
The rhizomes of Ginger (Zingiberofficinale), Turmeric (Curcuma longa), Licorice (Glycyrrhizaglabra), the bark of Cinnamon tree,(Cinnamomumzeylanicum) and the calyces of red Roselle (Hibiscus sabdariffa L.)are herbs used in thishepatoprotective studies. This study evaluates the hepatoprotective activity of water extract mixtures using carbon tetrachloride (CCl4)-induced liver injury in rats.In vitroantioxidant activity of plant water extracts was determined using DPPH. The water extractmixtures wereadministered for 10 days; on the 10thday all rats were challenged with CCl4 except control group animals. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin levels were determined to prove the hepatoprotectiveeffect.The enzyme activities were significantly increased in CCl4 treated rats. The four water extract mixtures exhibited significant (P<0.05) protective effect against CCl4-induced hepatoxocity and nephrotoxicity by decreasing the levels of serum markers, specially AST and creatinine , respectively.On the other hand, the serum lipid profiles were slightly improved ; HDL-cholesterol significantly (P<0.05) increased in all the water extract mixtures used.