Cannabis sativa exacerbates hepatic injury caused by acetaminophen or carbon tetrachloride in rats

The effect of Cannabis sativa extract on acute liver injury caused by acetaminophen or carbon tetrachloride (CCl₄) was studied in rats. Cannabis sativa was given at doses of 5 or 10 mg/kg (expressed as Δ⁹-tetrahydrocannabinol) once daily intraperitoneally (i.p.) for 2 days and simultaneously with acetaminophen or CCl₄. Rats were killed 24 h after acetaminophen or CCl₄ administration. Reduced glutathione (GSH), lipid peroxidation (malondialdehyde; MDA) and nitric oxide (nitrite/nitrate) concentrations were measured in the liver. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were determined in serum. Hepatic injury was also determined via histological examination of liver sections. The administration of only cannabis for 2 days had no significant effect on serum liver enzymes or on the hepatic levels of GSH, MDA or nitric oxide. However, in rats intoxicated with acetaminophen, Cannabis sativa at 5 or 10 mg/kg resulted in a significant increase in serum GOT by 17.6% and 19.5%, respectively, compared with the acetaminophen control group. In the CCl₄-induced acute liver injury, the levels of AST, ALT and ALP in serum were significantly elevated by Cannabis sativa extract in a dose-dependent manner by 23.7–29.1%, 14.4–21.3% and 17.6–22.1%, respectively. In both models of hepatic injury, Cannabis sativa resulted in a significant increase in the level of liver MDA and nitric oxide and a significant decrease in GSH compared with the corresponding acetaminophen or CCl₄ control group. These changes were dose dependent. Histological examination showed an increase in centrilobular necrotic areas in acetaminophen or CCl₄-treated rats administered with Cannabis sativa. Histochemical investigation revealed a decrease in intracellular protein contents caused by CCl₄ or acetaminophen, and these were further decreased by Cannabis sativa. It is concluded that short-term administration of Cannabis sativa enhances acute hepatic damage caused by CCl₄ or acetaminophen in rats.     

Effect of Crataegus extract on carbon tetrachloride-induced hepatic damage

The current study evaluated the effect of a standardized Crataegus extract on liver injury induced by acute carbon tetrachloride (CCl₄) administration in rats. Crataegus extract (10, 20 or 40?mg/kg), silymarin (25?mg/kg) or saline (control) was given once daily orally simultaneously with CCl₄ and for 1?week thereafter. Crataegus extract given at the above doses reduced serum alanine aminotransferase (ALT) levels by 28.8, 31.8 and 36.4%, respectively, when compared to the CCl₄ control group. Serum aspartate aminotransferase (AST) levels decreased by 14.3, 15.5 and 20.6%, respectively, while alkaline phosphatase (ALP) decreased by 21.8% by the extract at 40?mg/kg. The administration of silymarin reduced ALT, AST and ALP levels by 66.8, 64.9 and 60%, respectively. In CCl₄-treated rats, the increase in serum nitric oxide (nitrite/nitrate) level, the histological liver damage as well as the decrease in mucopolysaccharide and protein content of hepatocytes were all improved by Crataegus extract at 40?mg/kg and almost normalized by silymarin. These results suggest that treatment with Crataegus extract improves the CCl₄-induced hepatic injury in rats.     

Antioxidant effects of Citharexylum spinosum in CCl4 induced nephrotoxicity in rat

The present study was carried out to evaluate the antioxidant effect of the chloroform extract of Citharexylum spinosum (CSCE) (Family: Verbenaceae) leaves in Sprague–Dawley male rats. The different groups of animals were administered with carbon tetrachloride (CCl₄; 20% in olive oil, 2 ml/kg body weight) 7 doses (i.p.) at 48 h interval. The CSCE at the doses of 100 and 200 mg/kg or silymarin at a dose of 50 mg/kg were administered intragastrically after 24 h to the CCl₄ treated rats. The effect of CSCE or silymarin on urine and serum markers (urea, creatinine, creatinine clearance, protein, albumin, urobilinogen and nitrite) was measured in CCl₄-induced nephrotoxicity in rat. Further, the effects on lipid peroxidation (TBARS), enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase) and non-enzymatic antioxidant glutathione (GSH) were estimated in the kidney samples. The CSCE and silymarin produced significant renal protective effects by restoring the concentration of urine and serum markers. Activity level of antioxidant enzymes and GSH contents were increased while lipid peroxidation (TBARS) was decreased, dose dependently with CSCE and silymarin. Decrease in body whereas increase in kidney weight induced with CCl₄ was restored with CSCE and silymarin. Chemical composition of CSCE indicated the presence of flavonoids, terpenoids, alkaloids and very low amount of saponins. Total flavonoids estimated were (127 ± 14.6) as rutin equivalent mg/g of the extract. From these results, it is suggested that CSCE possesses potent nephroprotective and antioxidant properties.     

Hepatoprotective effects of Lycium chinense Miller fruit and its constituent betaine in CCl4-induced hepatic damage in rats

The hepatoprotective activities of Lycium chinense Miller (LC) fruit extract and its component betaine were investigated under carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. The treatment of LC fruit extract significantly suppressed the increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the sera of CCl₄ injured rats, and restored the decreased levels of anti-oxidant enzymes such as total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and suppressed the expression of inflammatory mediators including inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-1 and -2. To visualize the potential activity of betaine, a component of LC fruit, betaine was substituted for LC extract in CCl₄ injured rats. The biochemical profile in CCl₄ injured rats co-treated with betaine matched those of LC fruit treated CCl₄ injured rats. The ameliorative effects of LC extract, as well as betaine, were also confirmed by histopathological examination. Collectively, the present findings imply that LC fruit, via its component betaine, mitigate CCl₄-induced hepatic injury by increasing antioxidative activity and decreasing inflammatory mediators including iNOS and COX-1/COX-2.     

Chlorella vulgaris extract ameliorates carbon tetrachloride-induced acute hepatic injury in mice

The possible protective effects of Chlorella vulgaris extract (CVE) on carbon tetrachloride (CCl₄)-induced acute hepatic injury in mice and the mechanism underlying these effects was investigated. CCl₄ administration caused a marked increase in the levels of serum aminotransferases, lipid peroxidation and cytochrome P450-2E1 (CYP450) expression. Also, decreased glutathione (GSH) content and activities of cellular antioxidant defense enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and glutathione-S-transferase (GST) were found after CCl₄ exposure. All of these phenotypes were markedly reversed by preadministration of the mice with CVE. In addition, CVE exhibited antioxidant effects on FeCl₂–ascorbate induced lipid peroxidation in mouse liver homogenates, and on superoxide radical scavenging activity. Taken together, these results suggest that CVE produced a protective action on CCl₄-induced acute hepatic injury in mice, presumably through blocking CYP-mediated CCl₄ bioactivation, inducing the GSH levels, antioxidant enzyme activities and free radical scavenging effect. Therefore, CVE may be an effective hepatoprotective agent and viable candidate for treating hepatic disorders and other oxidative stress-related diseases.     

Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders

Background  

Carbon tetrachloride (CCl₄) is a well-known hepatotoxin and exposure to this chemical is known to induce oxidative stress and causes liver injury by the formation of free radicals. Acute and chronic renal damage are also very common pathophysiologic disturbances caused by CCl₄. The present study has been conducted to evaluate the protective role of the aqueous extract of the bark of Termnalia arjuna (TA), an important Indian medicinal plant widely used in the preparation of ayurvedic formulations, on CCl₄ induced oxidative stress and resultant dysfunction in the livers and kidneys of mice.     

Mangiferin, a natural polyphenol protects the hepatic damage in mice caused by CCl4 intoxication

Mangiferin is a natural polyphenolic (C-glucoxyl xanthone) antioxidant present in the bark, fruits, roots and leaves of Mangifera indica Linn. In the present study, we investigated the protective effect of mangiferin against carbon tetrachloride (CCl₄)-induced hepatotoxicity in mice and compared it with silymarin, a standard hepatoprotective drug. The pretreatment of mangiferin (30?mg/kg body weight, i.p.) has shown it to possess a significant protective effect by lowering the serum aspartate and alanine aminotransferases, alkaline phosphatase, bilirubin and inflammatory mediator TNF-α. This hepatoprotective action was confirmed by histological observation. In addition, pretreatment of mangiferin prevented the elevation of hepatic malondialdehyde formation and the depletion of antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and total reduced glutathione) activity in the liver of CCl₄-injected mice. The results suggest that mangiferin exhibits potent hepatoprotective effects on CCl₄-induced liver damages in mice.     

Dietary honey and ginseng protect against carbon tetrachloride-induced hepatonephrotoxicity in rats

Liver diseases are amongst the most serious health problems in the world today and hepatocellular carcinoma is one of the world's deadliest cancers. The aim of the current study was to evaluate the protective effect of sider honey and/or Korean ginseng extract (KGE) against carbon tetrachloride (CCl₄)-induced hepato-nephrotoxicity in rat. Eighty male Sprague-Dawley (SD) rats were allocated into different groups and over a 4-week period, they orally received honey and/or KGE or were treated either with CCl₄ alone (100 mg/kg b.w) or with CCl₄ after a pretreatment period with honey, KGE or a combination of both. Clinical, clinico-pathological and histopathological evaluations were done and CCl₄-treated groups were compared with rats receiving no treatment and with rats given honey, KGE or a combination of these substances. The results indicated that oral administration of CCl₄ induced severe hepatic and kidney injury associated with oxidative stress. The combined treatment with CCl₄ plus honey and/or KGE resulted in a significant improvement in all evaluated parameters. This improvement was prominent in the group receiving CCl₄ after combined pretreatment with honey and KGE. Animals receiving honey and/or KGE (without CCl₄-treatment) were comparable to the control untreated group. It could be concluded that honey and KGE protect SD rats against the severe CCl₄-induced hepatic and renal toxic effects. Our results suggest that the protective activity of honey and KGE may have been related to their antioxidant properties.     

The role of heat shock protein 70 induced by geranylgeranylacetone in carbon tetrachloride-exposed adult rat testes

Carbon tetrachloride (CCl₄) induces testicular damage, through formation of free-radical metabolites. Molecular chaperone heat shock protein of 70 kDa (HSP 70) protects cells from various stresses. This study was designed to investigate the potential role of induction of HSP70 using geranylgeranylacetone (GGA) on testicular damage caused by CCl₄. Rats were divided into group I (control group), Group II (CCl₄ group) received CCl₄ s.c. for 4 weeks, group III received CCl₄ s.c. for 4 weeks simultaneously with daily single oral dose of GGA (GGA – treated CCl₄ group). Serum testosterone, testicular lactate dehydrogenase (LDH) and alkaline phosphatase (ALP), testicular malondialdehyde (MDA), total nitrite and total antioxidant capacity (T-AOC) were measured. Evaluation of histopathological changes and immunohistochemical HSP70 expression for testicular biopsies were performed. Group II showed lower values of gonado-somatic index, serum testosterone, testicular LDH, ALP, T-AOC and greater values of testicular MDA and total nitrite than in control. Testicular morphology showed widening of seminiferous lumen, less spermatogenesis, vacuolization of germinative epithelium. Group III had higher values of gonado-somatic index, serum testosterone, testicular LDH, ALP, T-AOC with less testicular MDA and total nitrite than in group II. They have less damage and restored the altered testicular morphology. Immunohistochemical HSP70 expression was increased in the testicular spermatogenic and sertoli cells in group II that was significantly accentuated in group III. These findings suggest that GGA-induced activation of HSP 70 significantly alleviate CCl₄ inflicting testicular damage by HSP 70 mediated cytoprotection and antioxidant effects.     

Hepatoprotective effects of Cynara extract and silymarin on carbon tetrachloride-induced hepatic damage in rats

The aim of this study was to investigate the effect of Cynara scolymus extract alone or in combination with silymarin on the carbon tetrachloride (CCl₄)-induced hepatic injury in rats. Cynara extract (30, 60, or 120 mg/kg), silymarin (25 mg/kg), or Cynara extract (30, 60, or 120 mg/kg) combined with silymarin was given once daily orally simultaneously with CCl₄ and for 2 weeks thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Cynara extract given at the above doses conferred significant protection against the hepatotoxic actions of CCl₄ in rats, reducing serum alanine aminotransferase (ALT) levels by 21 %, 24.3 %, and 35.8 %, respectively, compared to CCl₄ control group. Serum aspartate aminotransferase (AST) levels decreased by 15.5 %, 39.6 %, and 44.3 %, respectively. Alkaline phosphatase (ALP) decreased by 21 % and 25 % by Cynara extract at 60 and 120 mg/kg, respectively. In rats treated with silymarin combined with Cynara extract (30, 60, or 120 mg/kg), ALT decreased by 32.6 %, 34.5 %, and 51.6 %, and AST decreased by 20 %, 50.6 %, and 58.3 %, respectively. Meanwhile, ALP decreased by 22.4 % and 29.7 % after treatment with silymarin combined with Cynara extract (60 or 120 mg/kg). On the other hand, the administration of silymarin alone reduced ALT, AST, and ALP levels by 55.3 %, 67.1 %, and 52.5 %, respectively. The administration of CCl₄ resulted in marked increase in nitric oxide level in serum (the concentrations of nitrite/nitrate) as well as marked decrease in blood levels of reduced glutathione (GSH). Treatment with Cynara extract resulted in a dose-dependent decrease in serum nitric oxide level and increased GSH in blood compared with CCl₄ control group. Silymarin showed an additive effect resulting in further decrease in serum nitric oxide. Silymarin only treatment caused a marked reduction in serum nitric oxide level and increased GSH in blood. Histopathological studies also indicated that CCl₄-induced liver injury was less severe in Cynara extract-treated groups. Metabolic perturbations caused by CCl₄ in hepatocytes such as reduced protein and mucopolysaccharide content were markedly improved by the Cynara extract given at the dose of 120 mg/kg. Intracellular protein and mucopolysaccharide contents were normalized upon treatment with silymarin. The effect of Cynara–silymarin combination was, however, less than that of Cynara extract alone. These results suggest that treatment with Cynara extract protects against CCl₄-induced hepatic injury in rats and might prove of value in treating chronic liver disease in man, although the combination of Cynara–silymarin is not superior to either Cynara extract or silymarin alone.     

Effect of ethylene dibromide and carbon tetrachloride on lipid peroxidation in rat and chick liver

Lipid peroxidation in vitro of carbon tetrachloride (CCl₄) and ethylene dibromide (EDB) in microsomal supernatant fraction (MSF) of chick and rat livers was evaluated by measuring the malonaldehyde concentration after incubation with thiobarbituric acid.     

Protective Effect of Ssanghwa-Tang Fermented by Lactobacillus Fermentum Against Carbon Tetrachloride-Induced Acute Hepatotoxicity in Rats

Ssanghwa-tang (SHT) is a traditional herbal medicine formula that has been used for the development of physical strength, relief of pain, and the reduction of fatigue. In this study, we fermented SHT with Lactobacillus fermentum (L. fermentum), Lactobacillus gasseri (L.gasseri), or Lactobacillus casei (L.casei) to investigate the hepatoprotective effects of SHT and fermented SHT with Lactobacillus on carbon tetrachloride (CCl₄)-induced liver injury in rats. Rats were given CCl₄ (1 ml/kg, 50% CCl₄ in olive oil) intraperitoneally and either SHT or fermented SHTs (15 ml/kg) was administered 30 min before CCl₄. At 24 hr after CCl₄ injection, the levels of transaminases in the serum were markedly increased. These increases were significantly attenuated by either SHT + L. fermentum or SHT+ L.gasseri. However, SHT and SHT + L.casei showed slight suppression of the increase of transaminases. The liver histological changes were diminished by treatment with SHT + L. fermentum. Additionally, the potential hepatoprotective effect of fermented-SHTs correlated with the amount of unknown metabolite which is produced during fermentation process with L. fermentum, L.gasseri, or L.casei. Therefore, these results suggest that the hepatoprotective effect of SHT may be improved by fermentation with L. fermentum and the intestinal bacterial enzyme activities may likely play an important role in the pharmacological action of herbal medicines.     

Radon Inhalation Protects Mice from Carbon-Tetrachloride-Induced Hepatic and Renal Damage

We assessed whether radon inhalation provided protection from carbon tetrachloride (CCl₄)-induced hepatic and renal damage in mice. Mice were subjected to intraperitoneal injection of CCl₄ after inhaling approximately 18 kBq/m³ radon for 6 h. Radon inhalation significantly increased total glutathione (t-GSH) content and glutathione peroxidase (GPx) activity in the liver and kidney. Injection of CCl₄ was associated with significantly higher levels of glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (ALP) activity and creatinine level in serum, and pretreatment with radon significantly decreased the GOT and ALP activity and creatinine level associated with CCl₄ injection, suggesting that radon inhalation alleviates CCl₄-induced hepatic and renal damage. The t-GSH contents and GPx activity in the liver and kidney of animals pretreated with radon were significantly higher than those of the CCl₄-only group. These findings suggested that radon inhalation activated antioxidative functions and inhibited CCl₄-induced hepatic and renal damage in mice.     

Studies on fatty liver with isolated hepatocytes. II. The action of carbon tetrachloride on lipid peroxidation, protein, and triglyceride synthesis and secretion.

This report describes some effects of poisoning with carbon tetrachloride on hepatocytes in single cell suspension. In isolated liver cells as well as “in vivo” CCl₄ stimulates lipid peroxidation, inhibits both protein synthesis and protein and lipoprotein secretion and induces fat accumulation within the cells. As the action of CCl₄ on lipid peroxidation, our data confirm that its increase induced by CCl₄ depends on the metabolism of this drug by the NADPH-cytochrome P₄₅₀ enzyme system. Furthermore, data reported here suggest that the onset of the CCl₄-induced decrease of lipoprotein secretion is due to a derangement of the secretory pathway.     

Protective effect of Sonchus asper extracts against experimentally induced lung injuries in rats: A novel study

In this study, protective effects of methanol extract (SAME) were evaluated against carbon tetrachloride induced oxidative stress in lungs. Male Sprague–Dawley rats were orally fed with various doses (100, 200 mg/kg body weight) of SAME and (50 mg/kg body weight) of rutin after 48 h of CCl₄ treatment (3 ml/kg body weight, 30% in olive oil) biweekly for 4 weeks. The results showed that administration of extracts and rutin significantly restored lung contents of reduced glutathione and activities of catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, quinine reductase were reduced while lipid peroxide, hydrogen peroxide, nitrite, DNA fragmentation% and activity of γ-glutamyl transferase, increased by CCl₄, were reversed towards the control levels by the supplement of Sonchus asper extracts and rutin. Lung histopathology showed that S. asper extracts and rutin reduced the incidence of lung lesions induced by CCl₄ in rats. These results suggest that S. asper fractions and rutin could protect lung against the CCl₄-induced oxidative damage in rats.     

N-acetylcysteine protects against liver injure induced by carbon tetrachloride via activation of the Nrf2/HO-1 pathway

Chronic liver injury is an important clinical problem which eventually leads to cirrhosis, hepatocellular carcinoma and end-stage liver failure. It is well known that cell damage induced by reactive oxygen species (ROS) is an important mechanism of hepatocyte injure. N-acetylcysteine (NAC), a precursor of glutathione (GSH), is well-known role as the antidote to acetaminophen toxicity in clinic. NAC is now being utilized more widely in the clinical setting for non-acetaminophen (APAP) related causes of liver injure. However, the mechanisms underlying its beneficial effects are poorly defined. Thus, Aim of the present study was to investigate potential hepatic protective role of NAC and to delineate its mechanism of action against carbon tetrachloride (CCl₄)-induced liver injury in models of rat. Our results showed that the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as malondialdehyde (MDA) contents decreased significantly in CCl₄-induced rats with NAC treatment. GSH content and superoxide dismutase (SOD) activities remarkably increased in the NAC groups compared with those in CCl₄-induced group. Treatment with NAC had been shown to an increase in nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA levels. In conclusion, these results suggested that NAC upregulated HO-1 through the activation of Nrf2 pathway and protected rat against CCl₄-induced liver injure. The results of this study provided pharmacological evidence to support the clinical application of NAC.     

Hepatoprotective effect of acetonic and methanolic extracts of Heterotheca inuloides against CCl4-induced toxicity in rats

A model of hepatotoxicity by carbon tetrachloride (CCl₄) in rats was used in order to evaluate the protective potential of the acetonic and methanolic extracts of Heterotheca inuloides. Pretreatment with the two H. inuloides extracts attenuated the increase in the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) observed in CCl₄-induced liver injury. The protective effect was confirmed by the analysis of tissue slides stained with hematoxylin-eosin and periodic acid/Schiff’s reagent. Additionally, the two extracts are scavengers to the superoxide radical as was observed by electron paramagnetic resonance. Due to the fact that the methanolic extract resulted in a better protective effect in the previous experiments, it was used to investigate in more detail the mechanism of hepatoprotection. Quercetin, one of the main components of the extract, with known hepatoprotective and antioxidant activity was used as a positive control. Pretreatment of animals with the methanolic extract or quercetin, was associated with the prevention of 4-hydroxynonenal and 3-nitrotyrosine increase in the liver, two markers of oxidative stress. Furthermore, the decrease in the activity of several antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase in CCl₄-induced liver injury was alleviated by the pretreatment with H. inuloides methanolic extract or quercetin. These results suggest that the hepatoprotective capacity of H. inuloides methanolic extract is associated with its antioxidant properties, which would also explain the biomedical properties attributed to this plant.     

Coenzyme Q10 and Silymarin Reduce CCl4-Induced Oxidative Stress and Liver and Kidney Injury in Ovariectomized Rats—Implications for Protective Therapy in Chronic Liver and Kidney Diseases

Oxidative stress is one of the key factors in the pathophysiology of liver disease. The present study aimed to evaluate the potential impact of two antioxidants, namely coenzyme Q10 (CoQ10) and silymarin, on carbon tetrachloride (CCl₄)-induced oxidative stress and hepatic damage in ovariectomized rats. Female Long Evans rats were divided into six groups (n = 6): control, CCl₄, CCl₄ + CoQ10 (200 mg/kg), CCl₄ + silymarin (140 mg/kg), Control + CoQ10, and Control + silymarin. Plasma and tissues from liver and kidney were analyzed for oxidative stress parameters and antioxidant enzyme activities using biochemical assays. Infiltration of inflammatory cells and fibrosis were assessed by histological staining of tissue sections. Both CoQ10 and silymarin significantly lowered serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels that were detected to be higher in CCl₄ rats compared to controls. Significant reduction in CCl₄-induced elevated levels of oxidative stress markers malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was observed with both antioxidants. However, in control rats, CoQ10 and silymarin did not produce a significant effect. Histological analysis revealed that CCl₄ markedly increased the level of inflammatory cells infiltration and fibrosis in liver and kidney tissues, but this was significantly reduced in CCl₄ + CoQ10 and CCl₄ + silymarin groups. Taken together, our results suggest that CoQ10 and silymarin can protect the liver against oxidative damage through improved antioxidant enzyme activities and reduced lipid peroxidation. Thus, supplementation of the aforementioned antioxidants may be useful as a therapeutic intervention to protect liver health in chronic liver diseases.     

In Vitro Antioxidant and In Vivo Hepatoprotective Activity of Leave Extract of Raphanus Sativus in Rats Using CCL4 Model

Background

Raphanus sativus is reported to have a variety of biological activities. This work screened the hepato-protective and antioxidant activity of ethanol (ERS), and aqueous (ARS), extracts of leaves of Raphanus sativus in Carbon tetrachloride (CCl₄), model in rats.

Material and Methods

The extracts were subjected to antioxidant tests (Total reducing power and Total phenolic content), and preliminary phytochemical screening. A pilot study was done on 100 and 300 mg/kg extracts, form which 300 mg was chosen for further experiments. The albino rats (200–250 grams), were divided into 5 groups of 6 animals each (n=6). There were three control groups comprising of normal control (normal saline −1ml/kg), negative control group (CCl₄ 1ml/kg in olive oil in a ratio of 1:1 v/v), and positive control group (Silymarin 50mg/kg). The Test drugs were given in a dose of 300 mg/kg for both ERS and ARS extract for 7 days. Biochemical parameters (AST, ALT, Alkaline phosphatase, Total Bilirubin), histo-pathological examination of liver and in vivo antioxidant tests [CAT, GSH and MDA] were done.

Results

The phytochemical study showed the presence of flavanoids, terpenoids, alkaloids, saponins and sterols. A dose dependent increase in the oxidative potential was observed in both the extracts with total phenolic content 70.1 and 44.4 GAE/g extract for ERS and ARS respectively. ERS 300mg/kg showed a significant (p<0.001) increase in levels of AST, ALT and alkaline phosphatase as compared to negative control (percentage hepatoprotection =45.3%) while ARS 300 mg/kg (p<.01) group showed 30% hepatoprotection. The GSH (p<0.001) and CAT (p<0.05) in ERS and ARS were significantly increased while MDA levels were decreased (P< 0.01), as compared negative control. The findings were confirmed histo-pathological examination.

Conclusion

The ethanol and aqueous extract of Raphanus sativus have partial hepatoprotection against CCl₄ toxicity.     

Attenuation of CCl4-induced hepatic oxidative stress in rat by Launaea procumbens

Antioxidant effects of Launaea procumbens methanol extract (LPME) were evaluated against CCl₄-induced oxidative stress in liver of rat. 48 male rats were equally divided in to 8 groups (06 rats each). Group I (control) remained untreated, while Group II was given vehicles (olive oil and DMSO). Animals of Groups III, IV, V, VI and VII were injected intraperitoneally with CCl₄ (3 ml/kg b.w.; i.p., 20% CCl₄/olive oil) twice a week for four weeks. Group III received only CCl₄ while Group IV was given rutin (50 mg/kg b.w.). Group V, VI and VII were administered LPME at a dose of 100, 150 and 200 mg/kg b.w., respectively. Animals of Group VIII received LPME (200 mg/kg b.w.) alone. Oxidative stress induced with CCl₄ in liver was evident by a significant increase in triglycerides, total cholesterol, LDL-cholesterol, and enzymatic activities of AST, ALT, ALP, LDH, γ-GT activities in serum. Level of lipid peroxidation, nitrite, and hydrogen peroxide concentration, DNA injuries in liver samples was also increased with CCl₄. GSH concentration in liver was significantly decreased, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GST, GSR, QR. Co-treatment of rats with LPME and rutin prevented all the changes observed with CCl₄. Hepatic lesions and telomerase activity induced with CCl₄ was also suppressed with LPME and rutin. It is suggested that LPME effectively prevented the CCl₄-induced oxidative injuries in liver, possibly through antioxidant and/or free radical scavenging effects of flavonoids and phenolic compounds in the extract.