Efficiency of the leaves and fruits of Aegle marmelos methanol extract (L.) Correa and their relative hepatotoxicity induced by CCL4 and identification of their active constituents by using LC/MS/MS.

The methanol extracts of both leaves and fruits (MEL & MEF) of A. marmelos (L.) Correa (family Rutaceae) were analyzed by using analytical method based on liquid chromatography-tandem mass spectrometry (LC/MS/MS). The objective of this study was to identify the active constituents of (MEL & MEF) of A. marmelos. Six, alkaloids namely aeglemarmelosine, marmesiline aegelinoside, shahidine, anhydromarmeline and N-2-methoxy-2-(4-methoxyphenyl) ethylcinnamide and two flavonoids, rutin and kaempferol-3-O-rutinoside in leaves were identified. Two alkaloids marmesiline and shahidine in the methanol extracts of fruits, also have been identified. Moreover, the efficiency of extracts was performed for measuring the reducing hepatotoxicity effect induced by carbon tetrachloride (CCl4) in mice. Accordingly, several biochemical parameters were performed such as lipid profile in serum, liver functions enzyme activities, glycolytic enzyme activities. In addition, LDH and SDH were investigated. The results obtained demonstrated, significant increase in lipid profile, liver function biomarkers in addition to glycolytic enzyme activities in CCl4-induced hepatotoxicity. Histopathological examination confirmed the biochemical results. Treatment of intoxicated mice with (MEL & MEF) of A. marmelos showed amelioration signs in biochemical findings as well as at cellular level. It could be concluded that both MEL & MEF can be used clinically for their potential effect as a hepatoprotective that normalized liver function biomarkers, hepatic architecture and restore physiologically status of the body against CCl4 intoxication.

Dietary supplementation of some antioxidants against hypoxia.

The present study aims to clarify the protective effect of supplementation with some antioxidants, such as idebenone (200 mg/kg, ip), melatonin (10 mg/kg, ip) and arginine (200 mg/kg, ip) and their combination, on liver function (T. protein, albumin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase), energetic parameters (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, inorganic phosphate, total adenylate, adenylate energy charge and potential phosphate). The effect on glycolytic and glycogenolytic enzymes (glucose, glycogen, glycogen phosphorylase, pyruvate kinase and phosphofructokinase against hypoxia) was also studied. The drugs were administered 24 and 1 h prior sodium nitrite intoxication. All biochemical parameters were estimated 1 h after sodium nitrite injection. Injection of sodium nitrite (75 mg/kg, sc) produced a significant disturbance in all biochemical parameters of liver function, energetic parameters and glycolytic and glycogenolytic enzymes. Hepatic damage was confirmed by histopathological examination of the liver as compared to controls. The marked changes in hepatic cells induced by sodium nitrite were completely abolished by pretreatment with the drug combination, suggesting potential protection against sodium nitrite-induced hypoxia. It could be concluded that a combination of both idebenone and melatonin or idebenone and arginine provides potential protection against sodium nitrite-induced hypoxia by improving biochemical parameters and preserving liver histology.

Evaluation of the immunological effect of beta alanyl-l-histidine against Schistosoma mansoni antigens in rabbits.

INTRODUCTION: The influence of vaccination on healthy (non-infected) rabbits treated with Schistosoma mansoni egg antigens, cercariae, and worms as prophylactic agents against infection, and the benefit of beta alanyl-l-histidine treatment against Schistosoma mansoni infection were investigated. METHODOLOGY: This study involved individual injection of three Schistosoma mansoni antigens: soluble egg antigen (SEA), cercarial antigen preparation (CAP) and soluble worm antigen preparation (SWAP), in three rabbit groups, respectively. Three other groups each received the same specific antigen in conjunction with the administration of (beta alanyl-l-histidine) L-carnosine. Hepatic total protein, glycogen and glycogen phosphorylase, total serum protein and one diminution electrophoresis of protein fractions (180 KDa; 116 KDa; 97, 4 KDa, serum albumin 66 KDa; 48. 5 KDa; 29 KDa; 18.400 KDa; 14.200 KDa; 6.5 KDa) were measured in all the rabbit groups. RESULTS: Elevation in most parameters was observed in the immunized groups. Carnosine treatment of rabbit groups immunized with SEA, CAP and SWAP in comparison to the non-carnosine-treated immunized groups resulted in amelioration of serum protein fractions in all SEA and SWAP-immunized animals, and reduction in glycogen phosphorylase b in SWAP animals alone. In addition, changes in glycogen content were observed in the CAP-immunized group. CONCLUSION: L-carnosine has a beneficial effect in the amelioration of most biochemical parameters as a result of S. mansoni antigen immunization.

Protective effect of L-carnitine and coenzyme Q10 on CCl4-induced liver injury in rats.

This study provides an information about the mechanisms of liver injury induced by CCl(4), and determines the influence of administration of L-carnitine or/and CoQ10 as prophylactic agents against CCl(4) deteriorative effect. The study was carried out on 80 adult male albino rats divided into eight groups, 10 animals each, as follows: four normal groups (control, treated with L-carnitine, treated with CoQ10, and treated with a combination of Lcarnitine and CoQ10) and four liver injury groups treated with CCl(4) (control, treated with L-carnitine, treated with CoQ10, and treated with a combination of L-carnitine and CoQ10). Liver injury was induced by s.c. injection of a single dose of CCl(4) (1 ml/kg). L-carnitine (50 mg/kg/day) was given i.p. for four successive days 24 hours before CCl(4) injection, and CoQ10 (200 mg/kg) was given as a single i.p. dose 24 hours before CCl(4) injection. Animals were sacrificed 24 hours after CCl(4) injection, blood samples were withdrawn and liver tissue samples were homogenized. The levels of the following parameters were determined: hepatic reduced glutathione, serum ALT and AST, hepatic lipid peroxides, hepatic vitamin C, hepatic and serum total protein, serum albumin, serum sialic acid, serum nitrite, and serum and hepatic total LDH activities and LDH isoenzymes. The obtained data revealed that CCl(4) injection produced a significant decrease in reduced glutathione content, vitamin C, total protein and albumin levels. However, there was a significant increase in serum ALT and AST activities, lipid peroxides, sialic acid, nitric oxide, serum and hepatic total LDH activities. On the other hand, groups treated with L-carnitine or/and CoQ10 prior to CCl(4) injection showed an improvement in most parameters when compared with cirrhotic control group. It has been concluded that L-carnitine and coenzyme Q10 have a pronounced prophylactic effect against liver damage induced by halogenated alkanes such as carbon tetrachloride.

Bioimmunological responses to Schistosoma mansoni and Fasciola gigantica worm homogenates either with or without saponin.

BACKGROUND: In this study, we evaluated the biochemical, immunological, histopathological and antischistosomal activities of Schistosoma mansoni or Fasciola gigantica worm homogenates mixed either with or without saponin that was extracted from Atriplex nummularia. METHODOLOGY: The immunization schedule was based on subcutaneous administration of two doses (50 microg /100 microl PBS) of each homogenate with time intervals of 15 days. After 15 days of the last homogenate inoculation, all mice were challenged with 100 Schistosoma mansoni cercariae and sacrificed after two months. Free radical scavengers and liver function enzymes were determined in mice liver. Worm counting and the histopathological picture of the liver were also done. RESULTS: Immunization with Schistosoma or Fasciola worm homogenates, mixed either with or without saponin, recorded an amelioration of the free radical scavenger levels, liver function enzymes and reduction in worm burden, as well as improvement of the histological feature of the liver, the number and size of granuloma, evidence of increased immune reaction manifested by a lymphocytic cuff surrounding the granuloma, diminution of its fibrotic and collagen content, and destruction of Schistosoma ova. CONCLUSION: Fasciola or Schistosoma worm antigens mixed with or without saponin succeeded to eliminate the product of oxidative stress and assistance in immune-mediated destruction of eggs that ameliorate the histopathological picture of the liver cells and preserve its function.

Protective role of Juniperus phoenicea and Cupressus sempervirens against CCl(4).

AIM: To investigate the role of Cupressus sempervirens (C. sempervirens) and Juniperus phoenicea (J. phoenicea) extracts as therapeutic effect against CCl(4) with biochemical, histopathological evaluations. METHODS: A single intraperitoneal dose of 10% CCl(4) in olive oil (1 mL/kg body weight) was administered to a group of female Wister rats, sacrificed after 24 h (as the injury group). The other groups were given CCl(4) as described above and divided as follows: two groups of ten rats each were orally administered either J. phoenicea extract or C. sempervirens extract three times per week for six weeks and a further group administered CCl(4) was left for six weeks to allow self-recovery. At the end of experiment, the rats from all groups were sacrificed for sampling and for biochemical and histological analysis. RESULTS: Remarkable disturbances were observed in the levels of all tested parameters. On the other hand, rats injected with the toxic agent and left for one and a half month to self recover showed moderate improvements in the studied parameters while, treatment with both medicinal herbal extracts ameliorated the levels of the disturbed biochemical parameters. The group treated with J. phoenicea extract showed a remarkable improvement in comparison to the CCl(4) treated group. The C. sempervirens group revealing an even more remarkable effect showing histopathological liver& kidney profiles close to those of the control group. CONCLUSION: C. sempervirens and J. phoenicea leaf extracts show a remarkable effect in enhancing liver and kidney functions and may thus be of therapeutic potential in treatment hepatotoxicity and nephrotoxicity.