CCl4 In Corn Oil Research Articles

Attenuation of Carbon Tetrachloride – Induced Hepatoxicity by Dacryodes edulis Seeds Ethanolic Extract in Male Wistar Rats

Dacryodes edulis (African pear) seed has a long history of use in ethnomedicine. However, there is a paucity of information on its ameliorative potential on hepatic damage. In the present study, the potentials of D. edulis ethanolic seed extract (DET) in attenuating carbon tetrachloride (CCl4)-induced hepatotoxicity in male Wistar rats was assessed. Ninety male Wistar rats were divided into 3 groups (n = 10) designated: control, CCl4, and DET, respectively. Animals in the control group were administered 2 mL/kg body weight corn oil, while those assigned to CCl4 and DET groups were administered i.p. 30% CCl4 in corn oil (1:1 v/v) at 2 mL/kg. Treatment was administered once every 24 h consecutively for 72 h. Thereafter, control and CCl4 groups were treated once daily with 1 mL distilled water by gavage, while DET rats were treated once daily with 1500 mg/kg DET by gavage. At every 7 days interval and for 28 consecutive days, animals were starved overnight, weighed, and six rats from each group were sacrificed under anesthesia to collect blood and liver samples. After 28 days, remarkable improvements in feed intake, body weight, serum levels of hepatic function indicators, and hepatic histology were observed in DET rats compared to CCl4 rats. These results suggest a possible ameliorative potential of D. edulis ethanolic seed extract against CCl4-induced hepatic injury.

Silybum marianum seeds oil attenuates CCl4-induced hepatic fibrosis via regulation of inflammatory response and oxidative stress

This study focused on the antioxidant and anti-inflammatory effects of Silybum marianum seeds oil (SMSO) on carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats. Hepatic fibrosis was induced by interaperitoneally (i.p.) administered with 20% CCl4 in corn oil (1 ml/kg, twice a week for six weeks) in rats. Results showed that SMSO was highly effective in preventing the development of cirrhosis in CCl4 rats. The mechanisms of action of SMSO were probably associated with its ability to reduce the inflammatory response and its ability to block oxidative stress induced by CCl4. SMSO may be a potential candidate for the prevention and treatment of liver fibrosis.

ROLE OF WHEAT GERM OIL AGAINST CARBON TETRACHLORIDE-INDUCED NEUROTOXICITY IN BRAIN TISSUES OF ADULT MALE MICE

The present study aimed to evaluate the possible curative effect of wheat germ oil (WGO) against carbon tetrachloride (CCl4)-induced neurotoxicity accompanied to the oxidative stress in brain tissue of adult male mice. A total of 24 mice were divided into 4 groups, 6 animals for each group. Control group: received oral corn oil for 10 days (0.5 mL/kg body weight). Wheat germ oil (WGO) group: received corn oil (0.5 mL/kg body weight) orally for 2 days then WGO (1400 mg/kg body weight) for 8 days. Carbon tetrachloride (CCl4) group: received CCl4 in corn oil orally (0.5 mL/kg body weight) for 2 days then received corn oil (0.5 mL/kg body weight) for 8 days. WGO+ CCl4 group: received CCl4 in corn oil (0.5 mL/kg body weight) orally for 2 days then WGO (1400 mg/kg body weight) for 8 days. Administration of CCl4 induced increment in malondialdehyde (MDA), nitric oxide (NO), oxidized glutathione (GSSG), 8-hydroxy-2-deoxyguanosine (8-OHdG), adenosine di- and mono-phosphates (ADP & AMP), while caused drop in reduced glutathione (GSH), adenosine triphosphate (ATP) and monoamines in brain tissues. Administration of WGO could reduce neurotoxicity and mitochondrial dysfunction caused by CCl4. WGO exhibited curative effect in restoring energy production, improving oxidative status, reducing DNA degradation and modulating neurotransmitters levels. In conclusion, CCl4-induced neurotoxicity aggravated the oxidative stress in brain tissues, causing DNA fragmentation, inhibited energy production and suppressed monoamines release. One the other hand, administration of WGO attained improvement in the aforementioned negative changes.

In vivo protective effect of phosphatidylcholine on carbon tetrachloride induced nephrotoxicity

Phosphatidylcholine (PC) from egg yolk is a bioactive substance with various beneficial effects, including anti-inflammatory and anti-oxidant effects. Recently, this substance has been reported to prevent acute hepatotoxicity. In the present study, we aimed to evaluate the putative protective effect of PC on carbon tetrachloride (CCl4)-induced nephrotoxicity in ICR mice. Many previous studies demonstrated that CCl4 induces nephrotoxicity resulting in renal oxidative damage. CCl4 in corn oil (0.1ml, 1.2g/kg) was intra-peritoneally injected into 7-week-old ICR mice twice a week. PC in corn oil (0.1ml, 100mg/kg) was then orally injected daily for a week. In 7 days, blood urea nitrogen (BUN) and creatinine concentrations had significantly increased in the CCl4 group compared to the control group, whereas the PC and CCl4 co-injected group had significantly decreased BUN and creatinine concentrations compared to the CCl4 group. Comparative analysis of histopathological injuries revealed that PC abrogated the nephrotoxicity of CCl4 at 7 days. Accordingly, PC also improved renal fibrosis induced by CCl4. Various biomarkers associated with oxidative damage appeared to be up-regulated in the CCl4 group, whereas in the PC and CCl4 co-injected group, levels of oxidative damage significantly decreased. Aquaporin1 (AQP1), an important water transport protein in the kidney, was down regulated in the CCl4 group compared to the control group. PC counteracted this effect. These results strongly suggest that PC can protect against oxidative damage induced by CCl4 in the kidney and enhance recovery from renal disorders.

Protective effects of sesamin on liver fibrosis through antioxidative and anti-inflammatory activities in rats

Context: Sesamin (Ses) from Sesamun indicum seeds has potent antioxidants and anti-inflammatory effects.Objective: This study focused on the antioxidant and anti-inflammatory effects of Ses on Carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats and the potential mechanism underlying the activation of NF-kB pathway.Materials and methods: Hepatic fibrosis was induced by interaperitoneally (i.p.) administered with 20% CCl4 in corn oil (2 mL/kg for 8 weeks) in rats. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were checked. The levels of protein carbonyls and antioxidant enzymes such as superoxide dismutase (SOD) and GSH-Px were determined after Ses administration. H&E and Masson’s trichrome staining for histopathological changes of liver tissues were observed. Western blotting was used to detect expression of IL-6, cyclooxygenase-2 (COX-2), and NF-kB activation. Finally, the levels of hydroxyproline in liver tissues were also determined.Results: Ses decreased the release of liver enzymes – ALT, AST, and TBIL, reduced protein carbonyls, attenuated the reduction of SOD and GSH-Px activities induced by CCl4 in the liver tissue. It also significantly reduced the levels IL-6 and COX-2 in the liver caused by CCl4 by inhibition of NF-kB activation. Histological results indicated that Ses significantly improved the pathological lesions of liver fibrosis.Conclusions: Ses exerted hepatoprotective effects possibly due to the antioxidant effect and suppressing the NF-kB activation.

Green tea extract attenuates CCl4-induced hepatic injury in male hamsters via inhibition of lipid peroxidation and p53-mediated apoptosis

Keeping in mind the beneficial effects of GTE administration on liver damage, the present study was undertaken to evaluate the hepatoprotective effect of green tea extract (GTE) against carbon tetrachloride (CCl4)-induced liver injuries in male hamsters for 8 weeks. Twenty hamsters were equally divided into 4 groups, the control ones (group I) received only dis. water. Hamsters of group II had free access to 10% of GTE, while hamsters of group III received 1ml/kg of 50% CCl4 in corn oil via gavage daily. Hamsters of group IV (GTE+CCl4) received a free access to GTE supplementation in combination with 1ml/kg of 50% CCl4 in corn oil via gavage daily. Lipid profile, hepatic enzyme levels and apoptosis molecular marker (p53) were investigated in hamsters. GTE+CCl4 treated hamsters showed lower levels of hepatic malondialdehyde (MDA) than CCl4 exposed hamsters. Hepatic activity levels of GSH, ALD and cytochrome 450 reductase were declined after CCl4 administration while they were remarkably improved with GTE administration. Serum lipid profiles as T-cholesterol (TC), triglyceride (TG) and low density lipoproteins (LDL) were improved in GTE and CCl4 treated hamsters than CCl4 group. Moreover, hepatic tissue damage and p53 expression induced with CCl4 were improved with the treatment of GTE. These results suggested that GTE possesses hepatoprotective properties against the effect of CCl4.

Restorative effect of (5E, 13E)–5,13–Docosadienoic acid on carbon tetrachloride induced oxidative stress in rats

ObjectiveTo evaluate the restorative effect of (5E, 13E)–5,13–Docosadienoic acid on carbon tetrachloride induced oxidative stress in rats. MethodsWistar strain male albino rats, weighing 180-200 g/bw were selected for the study. Rats were divided into four groups. Group I animals were served as normal control. Group II was administered with corn oil (3 ml/kg, i.p.) as vehicle control. Group III was given single dose (29th day) of CCl4 in corn oil (1:1 v/v, 3 ml/kg, i.p.). Groups IV was treated with (5E, 13E)–5,13–Docosadienoic acid (DA) (6 mg/kg body weight) for 28 days and given single dose of (29th day) CCl4 in corn oil (1:1 v/v, 3 ml/kg, i.p.). Six hours after CCl4 intoxication, the experimental animals were sacrificed. The blood samples were collected. Liver was excised immediately and immersed in physiological saline. ResultsThe lipid peroxidation was initiated in CCl4 intoxicated rats which is evidenced by thiobarbituric acid (TBARS) and diminution of GSH content in liver. Super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), vitamin C and E in CCl4 intoxicated rats retrieved towards near normalcy. After treating with DA which significantly altered (P<0.001) serum marker enzyme level and antioxidant level near normal against CCl4 treated rats. ConclusionsIt was observed that the entire variable tested i.e., SOD, CAT, GPx, reduced glutathione, vitamin C and E recorded a significant decline on CCl4 treatment. However, treatment with DA restored the levels to near normal value, suggesting the therapeutic effect of DA to counter the oxidative stress.

Decrease in Protein Kinase and Phosphatase Activities in the Liver Nuclei of Rats Exposed to Carbon Tetrachloride

The alteration in protein kinase and phosphatase activities in the liver nuclei of rats administered carbon tetrachloride (CCl4) was investigated. Rats received a single oral administration of CCl4 (1 ml/100 g body wt of 5, 10, and 25% CCl4 in corn oil), and 5, 24, and 48 h later they were euthanized by bleeding. The administration of CCl4 (10 and 25%) caused a significant decrease in protein kinase activity in the liver nuclei. The enzyme activity in the liver nuclei from normal and CCl4-administered rats was significantly increased by the addition of Ca2+ (0.5 mM) and calmodulin (10 μg/ml) in the reaction mixture, suggesting that Ca2+/calmodulin-dependent protein kinase activation is not suppressed by CCl4 treatment. Liver nuclear phosphatase activity toward phosphotyrosine, but not phosphoserine and phosphothreonine, was markedly decreased by CCl4 (5, 10, and 25%) administration. This decrease was seen 5 h after CCl4 administration. The presence of vanadate (10−4 M) in the reaction mixture caused a significant decrease in phosphotyrosine phosphatase activity in the liver nuclei from normal and CCl4-administered rats, whereas the enzyme activity was not decreased by okadaic acid (10−5 M) or sodium fluoride (10−3 M). The effect of anti-regucalcin antibody (100 ng/ml) in increasing phosphotyrosine phosphatase activity was seen in the liver nuclei of CCl4-administered rats, suggesting that regucalcin-sensitive phosphatase activity is decreased by CCl4 administration. The present study demonstrates that CCl4 administration induces a decrease in protein kinase and tyrosine phosphatase activities, which are involved in signaling factors in the liver nuclei of rats.

Liver nuclear DNA synthesis in mice following carbon tetrachloride administration or partial hepatectomy.

Long-term, continuous (twice per week) administration of CCl4 to male mice resulted in a high incidence of liver nodules which appeared to be resistant to the necrotizing effects of CCl4 but showed no features of malignant neoplasia. Liver nuclear DNA synthesis was compared in mice given CCl4 and in mice subjected to partial hepatectomy (PH). Mice were given by gavage corn oil or CCl4 in corn oil for periods of 2 to 25 weeks and several mice were subjected to PH after 12 and 25 weeks of corn oil treatment. Mice were given [3H]TdR during liver regeneration and newly synthesized liver nuclear DNA was isolated and separated by BND-cellulose chromatography. Greater than 85% of the labeled DNA from PH mice eluted from BND-cellulose columns as double-stranded (ds) DNA with single-stranded (ss) regions or ends and less than 15% as ds DNA. When mice were treated with CCl4 for 8 weeks or longer a significantly greater portion of liver nuclear DNA eluted as ds DNA. Administration of HU and 5-FU with [3H]TdR decreased [3H]TdR incorporation into DNA to low levels incompatible with unscheduled DNA synthesis. Single doses of CCl4 given to mice treated with corn oil for 2 to 12 weeks provided newly synthesized DNA which was primarily (greater than 80%) ds DNA with ss regions or ends, but after 25 weeks of corn oil administration, a single dose of CCl4 resulted in newly synthesized DNA with a greater proportion of ds DNA. The high labeling of ds DNA in mice treated with CCl4 may have resulted from an alternate pathway of DNA synthesis catalyzed by the enzymes or enzyme complexes associated with semiconservative DNA synthesis or from proliferation of nonparenchymal cells with a rapid turn-over rate.