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1.
Omar M. E. Abdel-Salam Amany A. Sleem Nermeen Shafee 《Comparative clinical pathology》2014,23(3):709-716
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. 相似文献
2.
Omar M. E. Abdel Salam Amany A. Sleem Nermeen Shafee 《Comparative clinical pathology》2012,21(6):1719-1726
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. 相似文献
3.
Omar M. E. Abdel-Salam Amany A. Sleem Nermeen Shaffie 《Comparative clinical pathology》2012,21(6):1149-1157
Extracts of Hypericum perforatum (St. John’s wort) have gained much interest for their antidepressant effects. The aim of the present study was to investigate the effect H. perforatum on the development of liver injury induced by treatment with carbon tetrachloride (CCl4) in rats. Liver damage was induced by administration of carbon tetrachloride (2.8?ml/kg in olive oil). H. perforatum (25, 50, and 100?mg/kg) alone or combined with silymarin (25?mg/kg) was given once daily orally simultaneously with CCl4 and for 14?days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. In CCl4-treated rats given H. perforatum at 25?mg/kg per day for 2?weeks, the elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum were significantly less than in the CCl4 control group. Serum ALT level decreased by 14.4% and AST level by 16.6% of their corresponding control value, respectively. Serum alkaline phosphatase (ALP) level was not significantly reduced by H. perforatum at 25?mg/kg. The addition of silymarin at the dose of 25?mg/kg to H. perforatum resulted in further decrease in liver enzymes compared with H. perforatum treatment alone. Serum ALT decreased by 40.2%, AST by 37.9%, and ALP by 38.1% of the control value, respectively, after combining H. perforatum at 25?mg/kg and silymarin. On the other hand, treatment with H. perforatum at 50 or 100?mg/kg reduced serum ALT levels by 37.9–52.6%, AST levels by 30.2–53.2%, and ALP by 48.5–51.5%, respectively. Silymarin given in combination with the above doses of H. perforatum reduced serum ALT by 58.7–63.3%, AST by 56.6–60.9%, and ALP levels by 54.7–58.8%, respectively. Meanwhile, silymarin alone decreased serum ALT by 56.8%, AST by 62.6%, and ALP levels by 55.1%, respectively. The administration of CCl4 resulted in marked increase in nitric oxide level in serum (the concentrations of nitrite/nitrate) as compared to the normal group. Treatment with H. perforatum resulted in a dose-dependent decrease in serum nitric oxide level compared with the CCl4 control group. Blood levels of reduced glutathione were markedly decreased in CCl4-treated rats. Reduced glutathione levels were increased significantly by 100?mg/kg H. perforatum and restored to near normal values by silymarin treatment. Histopathological examination also indicated that CCl4-induced liver injury was less severe in the H. perforatum-treated groups. Taken together, the present results show that H. perforatum reduces the extent of hepatic injury caused by CCl4 in rats and this effect is increased by co-administration of silymarin. This suggests the beneficial effect of silymarin administration to depressed patients with liver disease treated with H. perforatum. 相似文献
4.
Omar M. E. Abdel-Salam Amany A. Sleem Nermeen Shafee 《Comparative clinical pathology》2013,22(3):413-419
This study aimed to investigate the effect of piribedil, a drug used for the treatment of Parkinson’s disease and which has direct dopaminergic stimulating action, on the acute hepatic injury in mice. Hepatotoxicity was induced by CCl4 orally (0.28 ml/kg). Piribedil at three dose levels (4.5, 9, or 18 mg/kg) or silymarin (25 mg/kg) was given orally daily for 7 days, starting at time of administration of CCl4. Liver damage was assessed by determining liver serum enzyme activities and by hepatic histopathology. Piribedil administration lessened the increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) and also prevented the development of hepatic necrosis caused by CCl4. The effect of piribedil was dose-dependent one. Piribedil administered at the above doses caused significant reduction in the elevated plasma ALT by ?36.3%, ?42.8%, and ?52.4% and ALP by ?25%, ?36.9%, and ?57.1%, respectively. AST decreased by ?36.4% and ?46.2% by piribedil at 9 or 18 mg/kg, respectively. In comparison, the elevated serum ALT, AST, and ALP levels decreased to ?69.6%, ?64.2%, and ?68.5% of control values, respectively, by silymarin. Histopathologic examination of the livers of CCl4-treated mice administered piribedil at 9 mg/kg showed noticeable amelioration of the liver tissue damage, while piribedil at 18 mg/kg resulted in restoration of the normal architecture of the liver tissue as well as noticeable increase in the protein content of hepatocytes. It is concluded that administration of the dopaminergic agonist piribedil in a model of liver injury induced by CCl4 results in amelioration of liver damage. 相似文献
5.
Omar M. E. Abdel-Salam Amany A. Sleem Enayat Omara 《Comparative clinical pathology》2013,22(6):1145-1154
Micronised purified flavonoid fraction is a phlebotonic drug that is widely used in lower limb oedema due to chronic venous or lymphatic insufficiency. The aim of this study is to evaluate the effects of micronised purified flavonoid fraction (Daflon®) on hepatic injury caused by the administration of carbon tetrachloride (CCl4) in rats. Micronised purified flavonoid fraction (MPFF: 2.25, 4.5 or 9 mg/kg), silymarin (25 mg/kg) or MPFF (2.25, 4.5 or 9 mg/kg) combined with silymarin was given once daily orally simultaneously with CCl4 and for 1 week thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology and morphometry as well as by measuring the optical density of total alkaline phosphatase enzyme activity. Micronised purified flavonoid fraction given at the above doses conferred significant protection against the hepatotoxic actions of CCl4 in rats, reducing serum alanine aminotransferase (ALT) levels by 25.7, 43.1, and 75.6 %, respectively, compared to CCl4 control group. Serum aspartate aminotransferase (AST) levels decreased by 16.8, 35.6 and 62.9 %, respectively. Alkaline phosphatase (ALP) decreased by 17.9, 21 and 64.7 % by MPFF at 2.25, 4.5 and 9 mg/kg, respectively. In rats treated with MPFF–silymarin combination, ALT decreased by 27.5, 51.6, and 74.1 %, AST decreased by 38.4, 45.6, and 74.5 %, while ALP deceased by 44.3, 60.0, and 74.4 %. On the other hand, the administration of silymarin alone reduced ALT, AST and ALP levels by 78.9, 80.4 and 62.7 %, respectively. Histopathological studies also indicated that MPFF decreased the area of damage and improved hepatic architecture in CCl4-treated rats. In addition, MPFF markedly improved the optical density of total alkaline phosphatase enzyme activity. These results suggest that treatment with MPFF protects against CCl4-induced hepatic injury in rats and might find utility in treating chronic liver disease in man. 相似文献
6.
Omar M. E. Abdel-Salam Marwa El-Sayed El-Shamarka Nermeen Shaffee Alaa El-Din M. Gaafar 《Comparative clinical pathology》2014,23(3):495-507
Cannabis sativa preparations are the most widely used illicit drugs worldwide. The present study aimed to examine the effect of C. sativa extract on liver injury caused by thioacetamide in the rat. Thioacetamide was administered at 50 mg/kg twice weekly via subcutaneous route (s.c.) for 2 weeks. Starting from the first dose of thioacetamide, rats were treated with either C. sativa at doses of 10 or 20 mg/kg (expressed as Δ9-tetrahydrocannabinol), silymarin (25 mg/kg) or saline, once daily s.c., for 2 weeks. Reduced glutathione (GSH), lipid peroxidation (malondialdehyde; MDA) and nitric oxide concentrations were measured in the liver and brain. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), paraoxonase 1 activities (PON1) and total proteins were determined in serum. Hepatic injury was also determined via histological examination of liver sections. The administration of only cannabis to saline-treated rats had no significant effect on serum liver enzymes or on the hepatic levels of GSH, MDA or nitric oxide. Serum PON1 decreased by 21.9 % by 20 mg/kg cannabis. The level of MDA and nitric oxide in brain decreased by only cannabis administration. In thioacetamide-treated rats, the administration of cannabis extract (10 or 20 mg/kg) did not alter the level of MDA, GSH or nitric oxide in hepatic tissue. Serum ALT or AST were not significantly altered, but ALP increased significantly by 38.9 % after treatment with 20 mg/kg cannabis. Serum PON1 activity which showed marked decrease in thioacetamide-treated rats, increased by 18.9 and 151 % after C. sativa treatment. Serum proteins increased after the administration of cannabis (by 20.4 and 21.3 %, respectively). In brain tissue, both MDA and nitric oxide were significantly decreased by cannabis. Meanwhile, treatment with silymarin resulted in significant decrease in MDA and increased GSH in the liver tissue. Serum AST, ALT and ALP were significantly decreased, while PON1 activity was increased after silymarin. In brain, MDA decreased by 27.9 % after silymarin. Cannabis alone caused histological liver damage and fibrosis and neuronal degeneration. The liver tissue damage and brain degeneration caused by thioacetamide were enhanced by cannabis but almost prevented by silymarin treatment. It is concluded that the administration of C. sativa exacerbates the thioacetamide-induced liver and brain injury. 相似文献
7.
PV Habbu RA Shastry K M Mahadevan Hanumanthachar Joshi SK Das 《African journal of traditional, complementary, and alternative medicines》2008,5(2):158-164
The present study has been designed to evaluate the liver protective and in-vivo antioxidant role of Ethanolic extract (EtAS) and Ethyl acetate extract (EAAS) of roots of Argyreia speciosa, an important ‘rasayana’ herb in Indian System of medicine, in CCl4-induced hepatotoxicity and oxidative stress in rats. Animals were treated with EtAS and EAAS at doses of 200 mg and 400 mg / kg body weight p.o. along with CCl4 (0.7 ml / kg in olive oil, 1:1 v/v i.p. on every alternate days) for seven days. Serum biochemical parameters such as SGOT, SGPT, ALP, cholesterol, total and direct bilirubin were determined. Antoixidant status in liver was determined by measuring the activities of Super oxide dismutase (SOD), Catalase and Peroxidase. Histopathological study of isolated liver specimens was also carried out to know the protection offered by the extracts. There was a significant rise in the levels of serum GOT, GPT, and ALP and other biochemical parameters, decrease in the levels of SOD, Catalase and Peroxidase after administration of CCl4. Suspensions of EtAS and EAAS (200 and 400 mg/ kg) successfully prevented the alterations of these effects in rats (p< 0.001). Histopathological examination demonstrated that CCl4 treated group induces ballooning degeneration and centrilobular necrosis. Groups treated with EtAS and EAAS showed recovery on ballooning degeneration and centrlobular bridging necrosis was occasionally present. Data also showed that these extracts possessed strong antioxidant activity, and were comparable to Silymarin, a well known liver protecting herbal formulation. 相似文献
8.
Samanta Sifat Lamia Tushar Emran Jubaida Khatun Rikta Nowreen Islam Chowdhury Manoneeta Sarker Preeti Jain Tabinda Islam Zarin Tasnim Gias Manik Chandra Shill Hasan Mahmud Reza 《Pathophysiology》2021,28(1):50
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. 相似文献
9.
Omar M. E. Abdel-Salam Saffa Metwaly Amany Ameen Sleem Fatma Adly Morsy Hafiza A Sharaf 《Comparative clinical pathology》2013,22(2):209-218
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. 相似文献
10.
Jadwiga Jodynis-Liebert Teresa Adamska Magorzata Ewertowska Wiesawa Bylka Irena Matawska 《Experimental and toxicologic pathology》2009,61(5):443-451
Six groups of male Wistar rats were treated as follows: in groups II, III and V liver damage was induced by CCl4 (per os, 1590 mg/kg b.w. day) given 2 days a week for 6 weeks; group III was treated simultaneously with ethanol extract of Aquilegia vulgaris (100 mg/kg b.w. day) for 6 weeks; group V with silymarin, positive control, at a dose of 100mg/kg b.w. day for 6 weeks; and groups IV and VI received only the extract or silymarin, respectively. Microsomal lipid peroxidation in the liver increased following CCl4 treatment by 61–213% and was not changed significantly by the extract. The effect of silymarin was more pronounced, 19–52% decrease in the lipid peroxidation level. Hepatic glutathione was depleted by 22% in CCl4-treated rats. The extract tested did not change this parameter. The activity of antioxidant enzymes was significantly reduced after CCl4 administration, by 42–63%. Co-administration of the extract or silymarin resulted in significant increase in these enzymes activity; however, the basal level was not reached. Hepatic hydroxyproline concentration was elevated over 5-fold in comparison with controls. Co-administration of the extract or silymarin decreased the level of hydroxyproline by 66% and 55%, respectively. Activity of serum hepatic enzymes was elevated in rats treated with CCl4 by 47–8700%. Both the extract and silymarin reduced significantly these enzymes’ activity. The extract caused a fall in bilirubin and cholesterol level in rats treated with CCl4 by 42% and 17%, respectively. Histopathological examination revealed less-severe fibrosis in rats co-administered the extract or silymarin when compared to animals treated with CCl4 alone. 相似文献
11.
The possible modulatory effect of methanolic extract of Vernonia amygdalina (MEVA), a plant widely consumed in the tropics and used locally in the treatment of fever, jaundice, stomach disorders and diabetes on the toxicity of CCl4, was investigated in male rats.Oral administration of CCl4 at a dose of 1.2 g/kg body weight 3 times a week for 3 weeks significantly induced marked hepatic injury as revealed by increased activity of the serum enzymes ALT, AST, SALP and γ-GT. Methanolic extract of V. amygdalina administered 5 times a week for 2 weeks before CCl4 treatment at 250 and 500 mg/kg doses of the extract ameliorated the increase in the activities of these enzymes. Likewise the methanolic extract of V. amygdalina reduced the CCl4-induced increase in the concentrations of cholesterol, triglyceride and phospholipid by 37.8%, 30.6% and 8.5%, respectively, and a reduction in the cholesterol/phospholipids ratio. These parameters were however increased at 750 mg/kg extract pretreatment. CCl4-induced lipid peroxidation was likewise attenuated by 57.2% at 500 mg/kg dose of the methanolic extract of V. amygdalina. Similarly, administration of the extract increased the activities of the antioxidant enzymes: superoxide dismutase, glutathione S-transferase and reduced glutathione concentration significantly at 500 mg/kg (P<0.05) and catalase activity at 500–1000 mg/kg doses. These results suggest that methanolic extract of V. amygdalina leaves posseses protective effect against CCl4-induced hepatotoxicity by the antioxidant mechanism of action. 相似文献
12.
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. 相似文献
13.
Omar M. E. Abdel Salam Amany A. Sleem Nermeen Shafee 《Comparative clinical pathology》2012,21(1):77-89
The aim of the present study was to investigate the effect of several drugs acting on serotonergic neurotransmission on the
development of hepatocellular injury caused by carbon tetrachloride (CCl4) in rats. Liver damage was induced in rats by administration of CCl4 (2.8 ml/kg in olive oil, orally). Sertraline, citalopram, or fluvoxamine were administered orally once daily in association
with CCl4 and for 1 week thereafter. Sibutramine was administered 1 week prior to the toxic agent and for 3 days thereafter. Liver
damage was assessed by determining serum enzyme activities and hepatic histopathology. In CCl4-treated rats, sertraline (10, 20 mg/kg) reduced serum alanine aminotransferase (ALT) levels by 41.8% and 53.4%, respectively,
compared to controls. Serum aspartate aminotransferase (AST) levels decreased by 37.4% and 58.2%, respectively, while alkaline
phosphatase (ALP) decreased by 40.5% and 59.3%, respectively. Treatment with citalopram (5, 10, 20 mg/kg) reduced serum ALT
levels by 29.8%, 35.6%, and 43.8%, AST levels by 24.2%, 29.9%, and 43%, and ALP by 17.8%, 35%, and 48.9%, respectively. Fluvoxamine
(5, 10, 20 mg/kg) dose-dependently reduced the elevation of ALT levels by 42.6%, 49.9%, and 51.9%, AST levels by 40.2%, 44.6%,
and 61.6%, and ALP by 8.3%, 46.8%, and 52.7%, respectively. Given as a pretreatment, sibutramine (5, 10, 20 mg/kg) reduced
serum ALT levels by 52.1%, 52.2%, and 57.5%, AST levels by 53.6%, 58.4%, and 59.4%, and ALP by 46.8%, 67.6%, and 72.2%, respectively.
Histopathological and histochemical examinations also indicated that CCl4-induced liver injury was less severe after treatment with the test drugs than in the CCl4 control groups. It is concluded that the administration of drugs with serotonin reuptake inhibitory properties is associated
with a reduction in experimental liver injury induced by CCl4. 相似文献
14.
The hepatoprotective activity of cultured mycelium of morel mushroom Morchella esculenta against CCl4 and ethanol induced chronic hepatotoxicity was investigated. Hepatotoxicity was induced by challenging the animals with CCl4 (1:5, v/v, 3.75 ml/kg body weight, i.p., 30 doses) and ethanol (36%, v/v, 6 ml/animal, p.o., 35 doses) and the extract was administered at two concentrations (250 and 500 mg/kg body weight). Hepatoprotection was evaluated by determining the activities of liver function marker enzymes and antioxidant status of liver and also by histopathological observations of liver tissue. Administration of both ethanol and CCl4 elevated the levels of liver function enzymes, GOT, GPT and ALP in serum drastically. The treatment with the extract decreased the elevated serum GOT, GPT and ALP activities in a dose dependent manner. The extract also restored the depleted levels of antioxidants in liver consequent to CCl4 and ethanol challenge. The results indicated that aqueous-ethanolic extract of M. esculenta mycelium possessed significant hepatoprotective activity. The conclusion is also supported by the biochemical determinations and histopathological observations. The findings thus suggest the potential therapeutic use of morel mushroom mycelium as a novel hepatoprotective agent. 相似文献
15.
Diabetes mellitus is a metabolic disease resulting from defects in insulin secretion, insulin action, or both. Diabetes produces disturbances in lipid profile and increased incidence of atherosclerosis. Lipid abnormalitiesare defined by increases in triglyceride (TG), total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-c), low-density lipoprotein cholesterol (LDL-c), and decreases in high-density lipoprotein cholesterol (HDL-c). Silymarin is a natural hepato-protector extracted from Silybum marianum. It is possible that that Silymarin might be able to modulate metabolic changes in the liver and pancreas. In the present study, fifty adult male Wistar rats were used in five groups: group I—control (0.9 % NaCl), group II—diabetic control (0.9%NaCl), group III—diabetic receiving 100 mg/kg silymarin, group IV—diabetic receiving 125 mg/kg, silymarin, and group V—diabetic receiving 250 mg/kg silymarin. All groups were dosed for 14 days via oral gavage. Diabetes was induced by single injection of streptozotocin in rats (45 mg/kg b.w., ip.). Fasting glucose level and weight were measured before injection, 3 days after injection, and on days 7 and 14 of treatment. At the end of day 14, blood samples were collected via a heart puncture after animals had been anaesthetized with ether. Lipid profile of the serum samples were analysed (TC, TG, HDL-c, LDL-c). The results showed that hydroalcoholic extract of silymarin increased the average weight and decreased glucose level in this period, and TC, TG, LDL-c and VLDL-c level experienceda dose dependent reduction; the level of HDL-c increased in a dose-dependent manner at the end of 14 days (P?<?0/05). The results of the present study demonstrate that hydroalcoholic extract of silymarin has an overall beneficial effect on weight, glucose level and lipid profile in an experimental model. 相似文献
16.
Shariq Naeem Syed Waseem Rizvi Anil Kumar Aijaz Ahmad Khan Shagufta Moin Akif Ahsan 《African journal of traditional, complementary, and alternative medicines》2014,11(3):102-106
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. 相似文献17.
D Dahiru O Obidoa 《African journal of traditional, complementary, and alternative medicines》2008,5(1):39-45
Chronic alcohol ingestion is known to increase the generation of reactive oxygen species (ROS), thereby leading to liver damage. Antioxidant enzymes act individually or in combination to reduce or counter the effect of these ROS. Chronic administration of alcohol at (40% v/v, 1ml/100g), for 6 weeks showed a significant (p<0.05) elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). There was also a significant (p<0.05) decreased levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase compared to control rats. Pre-treatment of rats with 200, 400 mg/kg body weight of aqueous leaf extract of Ziziphus mauritiana or 100 mg/kg silymarin resulted in a significant (p<0.05) decreased levels of ALT, AST, ALP, and TB with levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase showing a significant (p<0.05) increase compared to group administered alcohol only. Histopathology of rat liver administered with alcohol only resulted in severe necrosis, mononuclear cell aggregation and fatty degeneration in the central and mid zonal areas which was a characteristic of a damaged liver. Pre-treatment with the aqueous extract of Ziziphus mauritiana or silymarin reduced the morphological changes that are associated with chronic alcohol administration. The presence of tannins, saponins and phenolic compounds observed in the plant extract could be responsible for the observed effects of decreasing the levels of injured tissue marker and lipid peroxidation. 相似文献
18.
Rahmat Ali Khan Muhammad Rashid Khan Sumaira Sahreen 《Experimental and toxicologic pathology》2013,65(3):319-326
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. 相似文献
19.
Neha Singh Neeraj Khullar Vandita Kakkar Indu Pal Kaur 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》2014,28(3):297-312
Background and Objectives
Curcumin, an established pleiotropic agent, has potential for hepatoprotection owing to its powerful antioxidant, anti-inflammatory, and antifibrogenic properties. However, its poor bioavailability limits its use in therapeutics. In this study, we aimed to package curcumin into solid lipid nanoparticles (C-SLNs) to improve its bioavailability and compare the efficacy of C-SLNs with that of free curcumin and silymarin, a well-established hepatoprotectant in clinical use, against carbon tetrachloride (CCl4)-induced hepatic injury in rats, post-induction. A self-recovery group to which no treatment was given was also employed for quantifying self-healing of hepatic tissue, if any.Material and Methods
C-SLNs (particle size 147.6 nm), prepared using a microemulsification technique, were administered to rats post-treatment with CCl4 (1 ml/kg body weight [BW] twice weekly for 2 weeks, followed by 1.5 ml/kg BW twice weekly for the subsequent 2 weeks). The extent of liver damage and repair in terms of histopathology and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), oxidative stress markers (malondialdehyde, superoxide dismutase, and reduced glutathione) and a pro-inflammatory response marker, tumor necrosis factor (TNF)-α, were determined in both the CCl4 group and the treatment groups.Results
C-SLNs (12.5 mg/kg) significantly (p < 0.001–0.005) attenuated histopathological changes and oxidative stress, and also decreased induction of ALT, AST, and TNF-α in comparison with free curcumin (100 mg/kg), silymarin (25 mg/kg), and self-recovery groups.Conclusion
Curcumin could be used as a therapeutic agent for hepatic disorders, provided it is loaded into a suitable delivery system. 相似文献20.
Bahman Mosallanejad Reza Avizeh Hossein Najafzadeh Varzi Mehdi Pourmehdi 《Comparative clinical pathology》2012,21(5):681-685
The aim of this study was to determine the protective action of silymarin on mebendazole-induced hepatotoxicity in cats. Twenty five healthy cats were randomly allotted into five equal groups. Cats in group A were given mebendazole (single dose 200?mg?kg, p.o.); group B consisted of cats that received silymarin (single dose 30?mg?kg, p.o.) concurrent with mebendazole administration; groups C, D and E were treated as group B, but silymarin was administered 2, 12 and 24?h after mebendazole administration, respectively. The serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total and direct bilirubin were measured before mebendazole administration and 2, 12, 24 and 72?h later as indices of liver injury. A single oral administration of mebendazole significantly elevated serum concentrations of ALT, AST, ALP, LDH (in all cases), and total and direct bilirubin in one cat in group A, after 24?h (P?<?0.05). In groups B and C, levels of serum enzyme activities and total and direct bilirubin remained within normal values, but in group D, levels of serum enzyme activity (in four cases) were higher than normal values and total and direct bilirubin remained within the normal range. In group E, levels of serum enzyme activities (in all cats) and total and direct bilirubin (in one cat) were higher than normal values. In conclusion, silymarin can protect liver tissue against oxidative stress in cats with mebendazole intoxication particularly in the first 2?h after exposure. 相似文献