Hepatoprotective Properties of Aqueous Leaf Extract of Persea Americana,Mill (Lauraceae) ‘Avocado’ Against CCL4-Induced Damage in Rats

Background

Natural products from plants have received considerable attention in recent years due to their diverse pharmacological properties, including antioxidants and hepatoprotective activities. The protective effects of aqueous extract of Persea americana (AEPA) against carbon tetrachloride (CCl₄)-induced hepatotoxicity in male albino rats was investigated.

Materials and Methods

Liver damage was induced in rats by administering a 1:1 (v/v) mixture of CCl₄ and olive oil [3 ml/kg, subcutaneously (sc)] after pre-treatment for 7 days with AEPA. Hepatoprotective effects of AEPA was evaluated by estimating the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and levels of total bilirubin (TBL). The effects of AEPA on biomarkers of oxidative damage (lipid peroxidation) and antioxidant enzymes namely, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were measured in liver post mitochondrial fraction.

Results

AEPA and Reducdyn® showed significant (p<0.05) hepatoprotective activity by decreasing the activities of ALT, AST, ALP and reducing the levels of TBL. The activities of antioxidant enzymes, levels of malondialdehyde and protein carbonyls were also decreased dose-dependently in the AEPA-treated rats. Pre-treatment with AEPA also decreased the serum levels of glutathione significantly.

Conclusion

These data revealed that AEPA possesses significant hepatoprotective effects against CCl₄-induced toxicity attributable to its constituent phytochemicals. The mechanism of hepatoprotection seems to be through modulation of antioxidant enzyme system.     

Biochemical and Toxicological Studies of Aqueous Extract of Syzigium Aromaticum (L.) Merr. & Perry (Myrtaceae) in Rodents

The effects of long-term administration of boiled aqueous extract of Syzigium aromaticum (SYZ), commonly known as clove (which has been locally employed for treating gastrointestinal tract diseases and also used as food spices), on some biochemical indices, such as body weight, liver functions and blood parameters were studied in adult albino rats of both sexes. Selected doses of 300 and 700 mg kg⁻¹ were given orally through cannular to groups of animals for a period of 90 days, while the control group received distilled water throughout the duration of study via the same route. Blood samples collected after therapy and assayed for activities of some liver enzymes recorded a significant (p<0.05) and prominent effect on ALP and AST. Measurement of haematological parameters also revealed significant effects (p<0.05; p<0.001) on Hb, RBC (p<0.05), PCV (p<0.001), platelets (p<0.001) and granulocytes (p<0.001). An insignificant reduction was recorded for total WBC. The histopathological study conducted was in consonance with the results of the biochemical investigations that the aqueous extract of SYZ even at moderate doses, significantly affects body organs, their enzymes as well as the various functions. LD₅₀ for both intraperitoneal and oral routes of SYZ were 263 and 2500 mg kg⁻¹ respectively. The present work has revealed the toxicity of sub chronic administration of SYZ, which suggests that its prolonged usage must be avoided.     

Comparative Anti-Inflammatory and Hepatoprotective Activities of Astragalus Gummifer Labill Herb and Roots in Rats

Background

The Astragalus gummifer (F. Fabaceae), herb and roots were studied for anti-inflammatory and hepatoprotective activities.

Materials and method

The alcoholic extracts of Astragalus gummifer (F. Fabaceae), herb (AGHE), and roots (AGRE), were used for anti-inflammatory and hepatoprotective activities in Wister rats. The effects of AGHE and AGRE were compared with the standard drugs Phenylbutazone and silymarin, for anti-inflammatory and hepatoprotective activities respectively.

Result

Both extracts showed significant anti-inflammatory activity (P< 0.001). AGRE showed comparatively more significant hepatoprotective activity (P< 0.001), than AGHE (P< 0.05); at doses of 250 and 500 mg/kg body weight as manifested by lowering the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin. The hepatoprotective activity was, also, supported by total protein (TP), malondialdehyde (MDA), nonprotein sulfhydryls (NP-SH), and histo-pathological studies of liver tissue.

Discussion

To the best of our knowledge, this is the first report of the anti-inflammatory and hepatoprotective activities of Astragalus gummifer. The results of present studies indicated that both AGHE and AGRE can be used in inflammatory conditions, while investigation supports the use of AGRE in cases that hepatoprotection are required in the hepatotoxic conditions. More supportive studies are required before clinical recommendation.     

Study of the effect of Cannabis sativa on liver and brain damage caused by thioacetamide

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.     

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.     

Protective Effects of Annona Muricata Linn. (Annonaceae) Leaf Aqueous Extract on Serum Lipid Profiles and Oxidative Stress in Hepatocytes of Streptozotocin-Treated Diabetic Rats

Extracts from various morphological parts of Annona muricata Linn. (Annonaceae) are widely used medicinally in many parts of the world for the management, control and/or treatment of a plethora of human ailments, including diabetes mellitus (DM). The present study was undertaken to investigate the possible protective effects of A. muricata leaf aqueous extract (AME) in rat experimental paradigms of DM. The animals used were broadly divided into four (A, B, C and D) experimental groups. Group A rats served as ‘control’ animals and received distilled water in quantities equivalent to the administered volumes of AME and reference drugs'' solutions intraperitoneally. Diabetes mellitus was induced in Groups B and C rats by intraperitoneal injections of streptozotocin (STZ, 70 mg kg⁻¹). Group C rats were additionally treated with AME (100 mg kg⁻¹ day⁻¹, p.o.) as from day 3 post STZ injection, for four consecutive weeks. Group D rats received AME (100 mg kg⁻¹ day⁻¹ p.o.) only for four weeks. Post-euthanization, hepatic tissues were excised and processed biochemically for antioxidant enzymes and lipid profiles, such as catalase (CAT), reactive oxygen species (ROS), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL), respectively. Treatment of Groups B and C rats with STZ (70 mg kg⁻¹ i. p.) resulted in hyperglycaemia, hypoinsulinaemia, and increased TBARS, ROS, TC, TG and LDL levels. STZ treatment also significantly decreased (p<0.05) CAT, GSH, SOD, GSH-Px activities, and HDL levels. AME-treated Groups C and D rats showed significant decrease (p<0.05) in elevated blood glucose, ROS, TBARS, TC, TG and LDL. Furthermore, AME treatment significantly increased (p<0.05) antioxidant enzymes'' activities, as well as serum insulin levels. The findings of this laboratory animal study suggest that A. muricata extract has a protective, beneficial effect on hepatic tissues subjected to STZ-induced oxidative stress, possibly by decreasing lipid peroxidation and indirectly enhancing production of insulin and endogenous antioxidants.     

Liver function recovery of COVID-19 patients after discharge,a follow-up study

Objective: The aim of this study was to observe the liver function recovery of COVID-19 patients after discharge.Patients and Methods: A total of 253 discharged COVID-19 patients in Shenzhen city, China were selected. The clinical characteristics of these patients were assessed. A 2-month follow-up and laboratory hematology test were performed to examine the status of patients'' liver function.Results: Patients combined with liver diseases, especially fatty liver, are more likely to progress to severe condition (P<0.05). Patients in severe condition and those with liver diseases have higher rates of liver injuries during hospitalization, characterized by a significant increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.01). The ALT, AST/ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and A/G levels showed significant differences in comparison with the control group (P<0.05, and P<0.001); and the outlier ratio of A/G, ALT, GGT and ALP of patients remained abnormal higher within 14 days after discharge (P<0.001). Liver injuries of COVID-19 patients may be related to the epidemiological characteristics, clinical indexes, basic diseases, symptoms, drug treatment during hospitalization and the complications. Indicators of liver function were correlated with cardiac function, renal function, thyroid function, lipid metabolism, glucose metabolism, immune index, leukocyte, erythrocyte, hemoglobin and platelet related indexes. The outlier ratio of TP, ALB and GLB remained extremely low throughout the follow-up period; the outlier ratio of ALT, AST and GGT decreased below 10% from a high level at 40 days after discharged. However, the outlier ratio of A/G, AST/ALT and ALP remained high during the follow-up period.Conclusions: Abnormal liver function might indicate worse recovery of COVID-19 patients. Changes in liver function should be emphasized during long-term follow-up of COVID-19 patients after hospital discharge; the necessity of employing appropriate interventions for liver function repair should be emphasized.     

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.     

Predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B patients and their diagnostic values in hepatic fibrosis

Objective: To investigate predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B (CHB) patients and their diagnostic values in hepatic inflammation and fibrosis. Methods: A total of 106 HBeAg-negative CHB patients with clinically and pathologically proven steatosis and 98 patients without steatosis were recruited into this study. The levels of fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), cholesterol (CHOL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), globulin (Glb), HBV DNA, body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR) and pathological changes of the liver in inflammation, fibrosis and fatty deposition were examined in all patients. Results: The levels of BMI, HOMA-IR, FBG, insulin, TG, and CHOL were significantly higher in patients with steatosis than those without steatosis (all P<0.05). But ALT, AST and HBV DNA levels were significantly lower in patients with steatosis (all P<0.05). Logistic regression analysis showed that only FINS was a significant predictor for hepatic steatosis (P<0.05); FINS and Glb were significant predictors for hepatic inflammation (all P<0.05); BMI and TC were significant predictors for hepatic fibrosis (all P<0.05). Conclusions: Hepatic steatosis, a common disease in HBeAg-negative CHB patients, was positively associated with BMI, FBG, FINS, TG, TC, GGT, ALP and HOMA-IR. In these patients, the prevalence of hepatic inflammation and fibrosis was also increased.     

Effect of Echinacea alone or in combination with silymarin in the carbon-tetrachloride model of hepatotoxicity

Echinacea preparations are widely used in the prevention or treatment of upper respiratory tract infections. The present study aimed to investigate the effect of a standardized Echinacea extract in experimentally induced liver toxicity and whether this herb would have a modulating effect on the silymarin-induced hepatoprotection in rats. Liver damage was induced by the administration of carbon tetrachloride (CCl₄). Echinacea extract (18 or 36?mg/kg) alone or combined with silymarin (25?mg/kg), silymarin only (25?mg/kg), or saline (control) was given once daily orally simultaneously with CCl₄ and for 1?week thereafter. Serum alanine aminotransferase (ALT) or aspartate aminotransferase were not significantly changed by treatment with Echinacea, but alkaline phosphatase (ALP) in serum decreased by 23.6% by the extract at 36?mg/kg. Silymarin given in combination with either dose of Echinacea resulted in 34.9% and 57.8% reduction in AST, 42.7% and 58% reduction in ALT and 41% and 60% reduction in ALP, compared with CCl₄ control group. Silymarin alone reduced ALT, AST, and ALP levels by 58.8%, 61.2%, and 62.2%, respectively. Histopathological examination revealed a mild decrease in degenerated hepatocytes after treatment with 36?mg/kg of Echinacea. Noticeable improvement in the liver damage was observed upon the addition of silymarin to Echinacea. A marked decrease of intracellular protein and glycogen staining was evident after the administration of CCl₄. Slight improvement in protein and glycogen staining was noted after 36?mg/kg of Echinacea. Increased hepatic protein and glycogen staining intensity was observed after silymarin and Echinacea co-treatment compared with Echinacea-only treated groups. Silymarin only treatment resulted in more or less normal histopathological and histochemical findings. The present results suggest that administration of Echinacea extract reduces the hepatoprotective effect of silymarin. Such finding is likely to have important clinical significance in patients with hepatic disease on silymarin treatment.     

Evaluation of prophylactic and therapeutic effects of silymarin on mebendazole-induced hepatotoxicity in cats

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.     

The effect of experimental streptococcus infection in myocarditis on some biochemical and inflammatory markers in albino rats

Background

Myocarditis is an uncommon disease that presents with a wide range of symptoms in children and adults. It is histologically characterized by varying degrees of myocardialnecrosis, edema and cellular infiltration myocardial inflammation is a nonspecificresponse to many triggers such as bacterial infection, cardio toxic agents, ormechanical injury.

Objective

This study was carried out to investigate the experimental Streptococcus faecalis induction of myocarditis and its effect on some blood parameters, inflammatory markers and histopathological changes in male albino rats.

Methods

Rats were infected by intraperitoneal injection of 10 8 CFU/ml of Streptococcus faecalis and sacrificed after one, two and seven days post infection. Biochemical analyses of blood were carried out to investigate the serum biomarkers of inflammation, liver function tests, cardiac enzymes & kidney function tests.

Results

All biochemical analyses showed statistically significant increase in the measured parameters due to bacterial infections except for blood urea which appear to be normal. A significant positive correlation was observed between lactate dehydrogenase enzyme (LDH) with creatinine (r =0.778, P<0.01). In the 7 days group, there were significant positive correlations between aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (r=0.675, P<0.05), erythrocyte sedimentation rate (ESR) with Urea (r=0.659, P<0.05) and alkaline phosphatase (ALP) with C-reactive protein (CRP) (r=0.765, p<0.01).

Conclusion

Many of these biomarkers will provide important new insights into pathophysiology and aid in the diagnosis and management of cardiovascular patients.     

Hepatoprotective Effect of Cymbopogon Citratus Aqueous Extract Against Hydrogen Peroxide-Induced Liver Injury in Male Rats

Background

Cymbopogon citratus (Poaceae) a tropical perennial herb plant that is widely cultivated to be eaten either fresh with food or dried in tea or soft drink has been reported to possess a number of medicinal and aromatic properties. This study aimed at evaluating the protective effects of C. citratus aqueous extract against liver injury induced by hydrogen peroxide (H₂O₂), in male rats.

Materials and Methods

Twenty-five rats were randomly divided into five different groups of five animals in each group; (1) Control. (2) Received H₂O₂ (0.5%) with drinking water. (3), and (4) received H₂O₂ and C. citratus (100 mg·kg⁻¹ b wt), vitamin C (250 mg·kg⁻¹ b wt) respectively. (5), was given C. citratus alone. The treatments were administered for 30 days. Blood samples were collected and serum was used for biochemical assay including liver enzymes activities, total protein, total bilirubin and malonaldehyde, glutathione in serum and liver homogenates. Liver was excised and routinely processed for histological examinations.

Results

C. citratus attenuated liver damage due to H₂O₂ administration as indicated by the significant reduction (p<0.05), in the elevated levels of ALT, AST, ALP, LDH, TB, and MDA in serum and liver homogenates; increase in TP and GSH levels in serum and liver homogenates; and improvement of liver histo-pathological changes. These effects of the extract were similar to that of vitamin C which used as antioxidant reference.

Conclusion

C. citratus could effectively ameliorate H₂O₂-induced oxidative stress and prevent liver injury in male rats.     

Hypericum perforatum protects against hepatic injury induced by carbon tetrachloride

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.     

Hepatoprotective and Antioxidant Effects of Argyreia Speciosa in Rats

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.     

Antidiabetic effect of kolaviron,a biflavonoid complex isolated from Garcinia kola seeds,in Wistar rats

Background

Hypoglycaemic effect of kolaviron (KV), (biflavonoid from Garcinia kola) in streptozotocin (STZ)-diabetic rats has been established.

Objectives

To evaluate the possible protective effects of KV on cardiac, renal and hepatic tissues of STZ-diabetic rats.

Methods

This study consists of four groups of 6 rats each. Groups one and two contained non-diabetic and untreated-diabetic rats, respectively. Groups three and four were made up of KV- and glibenclamide (GB) - treated diabetic rats, respectively.

Results

STZ-intoxication caused a significant (p<0.05) increase in the relative weight of liver in diabetic rats. STZ-diabetic rats had significant increase (p<0.05) in the levels of fasting blood glucose (FBG), á-amylase and HbA_1c. A marked and significant (p<0.05) increase in the levels of cardiac, renal and liver marker indices such as serum creatine kinase, lactate dehydrogenase, creatinine, urea and alanine aminotransferase were observed in untreated diabetic rats. Also, untreated diabetic rats had significantly (p<0.05) elevated urinary glucose and protein and, lowered creatinine clearance. In KV- and GB- treated groups, the levels of FBG, á-amylase and HbA_1c were significantly (p<0.05) reduced, while treatment with KV significantly (p<0.05) attenuated the cardiac, renal and liver marker indices.

Conclusion

KV offered significant antidiabetic and tissues protective effects in the rats.     

Effect of Administration of Aqueous Extract of Hippobromus Pauciflorus Leaves in Male Wistar Rats

The effect of administration of aqueous extract of Hippobromus pauciflorus (L.f.) Radlk (Sapindaceae) leaves at 50, 100 and 200 mg/kg body weight for 14 days on some biochemical parameters in male Wistar rats was investigated. The extract at all the doses tested did not significantly (P>0.05) alter the levels of white blood cells, red blood cells, mean corpuscular volume, platelets, neutrophils, monocytes, lymphocytes and large unstained cells. While the levels of haemoglobin, packed cell volume and basophils increased significantly (P<0.05) at specific doses, the mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and eosinophils decreased significantly (P<0.05). Again, the extract did not significantly (P<0.05) alter the computed liver- and kidney-body weight ratios, sodium, chloride and total protein, though, the levels of potassium, inorganic phosphorus, globulin, urea, total and conjugated bilirubin increased significantly (P<0.05) at certain doses. In contrast, the levels of albumin and creatinine also decreased significantly (P<0.05) at specific doses. While the activities of alkaline phosphatase, gamma glutamyl transferase and alanine aminotransferase remained significantly (P<0.05) unaltered in the serum, aspartate aminotransferase activity increased only at 200 mg/kg body weight. The atherogenic index as well as the concentrations of cholesterol, high- and low-density lipoprotein cholesterol in the serum of the animals were not significantly (P>0.05) altered. However, the extract significantly (P<0.05) increased the concentration of triacylglycerol. The results suggest that the extract has mild and dose specific haemato-, hepato- and nephrotoxic effects and may not be completely safe as oral remedy at the doses investigated.     

Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver

Endotoxemia-induced hepatotoxicity is characterized by disturbed intracellular redox balance, excessive reactive oxygen species (ROS) generation inducing DNA, proteins and membrane lipid damages. In the present study, the protective effects of montelukast (MNT) against Escherichia coli lipopolysaccharides (LPS)-induced oxidative stress were investigated in rat liver. LPS (10 mg/kg, i.p.) was injected and the animals were sacrificed 6 h after LPS challenge. MNT (10 mg/kg) was administered orally for seven successive days before endotoxemia induction. Blood samples were withdrawn for assessing the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and levels of serum total bilirubin, total protein, tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). Livers were dissected out and used for histological examination or stored for the determination of malondialdehyde (MDA), protein carbonyl content (PCC), reduced glutathione (GSH) levels, enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO). Sepsis significantly increased ALT, AST, ALP, LDH, total bilirubin, TNF-α and IL-1β, MPO, MDA and PCC levels and decreased total protein, GSH and enzymatic antioxidants (CAT, SOD and GSH-Px). MNT decreased the markers of liver injury (AST, ALT, ALP, LDH, and total bilirubin), inflammatory biomarkers (TNF-alpha, IL-1β), MDA, PCC and MPO after LPS challenge. In conclusion, MNT abrogates LPS-induced markers of liver injury and suppresses the release of inflammatory and oxidative stress markers via its antioxidant properties and enhancement enzymatic antioxidant activities.     

Preventive Effect of Geraniol on Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats

Background

Geraniol is a plant-derived phytochemical possessing anti-cancer action. The anti-carcinogenic effect of geraniol was investigated in the diethylnitrosamine (DEN)-induced hepatocarcinogenic rat model.

Methods

Male Wistar rats were intraperitoneally injected with 300 μL of phosphate-buffered saline (PBS) (G1; n = 4) or DEN (100 mg/kg body weight) dissolved in PBS (G2; n = 8) every 2 weeks on experimental weeks 2, 4 and 6. The rats were treated with a low concentration (0.07%) of geraniol (G3; n = 9) and high concentration (0.35%) of geraniol (G4; n = 7) for 12 weeks. To evaluate the effects of geraniol on the DEN-induced hepatocarcinogenesis, we compared the relative liver weight, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels and expression levels of proliferating cell nuclear antigen (PCNA) and glutathione S transferase-P (GST-P) by immunohistochemical analyses among each group.

Results

Relative liver weight was significantly higher in G2 than in G1 (P < 0.01). Both serum AST and ALT levels were significantly higher in G2 than in G3 and in G4 (P < 0.05). Serum ALP levels did not show a significant difference among each group. Percentages of both PCNA- and GST-P- positive area were significantly decreased in G3 and in G4 compared to in G2 (P < 0.001, respectively), suggesting anti-hepatocarcinogenic effects of geraniol.

Conclusion

Geraniol is a promising compound useful for suppression of hepatocellular carcinoma. The mechanisms of action are required to be clarified in the future intensive study.     

Anthelmintic Efficacy of Nauclea Latifolia Extract Against Gastrointestinal Nematodes of Sheep: In Vitro and In Vivo Studies

Direct effects of Nauclea latifolia extracts on different gastrointestinal nematodes of sheep is described. In vivo and in vitro studies were conducted to determine possible anthelmintic effect of leaf extracts of Nauclea latifolia toward different ovine gastro intestinal nematodes. A larval development assay was used to investigate in vitro, the effect of aqueous and ethanolic extracts of N. latifolia towards strongyles larvae. The development and survival of infective larvae (L₃) was assessed and best-fit LC₅₀ values were computed by global model of non-linear regression analysis curve-fitting (95% CI). Twenty sheep harbouring naturally acquired gastrointestinal nematodes were treated with oral administration of ethanolic extracts at a dose rate of 125 mg/kg, 250 mg/kg and 500mg/kg to evaluate therapeutic efficacy, in vivo.The presence of the extracts in the cultures decreased the survival of larvae. The LC₅₀ of aqueous and ethanolic extract were 0.704 and 0.650 mg/ml respectively and differ significantly (P<0.05, paired t test). Faecal egg counts (FEC) on day 12 after treatment showed that the extract is effective, relative to control (1-way ANOVA, Dunnett''s multiple comparison test), at 500mg/kg against Haemonchus spp, Trichostrongylus spp (p<0.05), Strongyloides spp (P < 0.01); at 250mg/kg against Trichuris spp (P < 0.01) and ineffective against Oesophagostomum spp (p>0.05). The effect of doses is extremely significant; the day after treatment is sometimes significant while interaction between dose and day after treatment is insignificant (2-way ANOVA).N. latifolia extract could therefore find application in the control of helminth in livestock, by the ethnoveterinary medicine approach.