Alterations in the lipid profiles and circulating liver enzymes in individuals infected by Schistosoma mansoni

Abstract INTRODUCTION Portal hypertension and periportal fibrosis commonly occur in severe Schistosoma mansoni infection. Changes in lipid profile and elevated levels of circulating liver enzymes have also been described in infected individuals. The present study sought to assess the alterations in laboratory parameters associated with liver disorder in individuals infected by S. mansoni who visited a private routine laboratory service. Levels of circulating liver enzymes (gamma-glutamyl transferase [γ-GT], aspartate transaminase [AST], alanine transaminase [ALT], and alkaline phosphatase [ALP]) and a lipid panel (total cholesterol [COL], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very low-density lipoprotein [VLDL], and triglycerides [TRI]) were evaluated in both infected and non-infected individuals and relative risk was used to measure associations. METHODS Data were collected for analysis from a total of 1,078 cases identified in 379,600 individuals who submitted samples to the Datalab Laboratory (Salvador, Bahia) between 2004 and 2008. RESULTS S. mansoni infection led to increased circulating levels of γ-GT in both women and men, AST (women), and ALP (men). S. mansoni infection was a protective factor against increased levels of TRI, CHO, and VLDL for individuals aged 19 years or older. The results of our analysis indicate that alterations in lipid metabolism and circulating liver enzymes in asymptomatic S. mansoni-infected individuals might be attributed to eggs lodged in the hepatic sinusoids. CONCLUSIONS Parasitological testing for S. mansoni should be indicated in endemic areas when this pattern of alterations is detected.

Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis

In this study, we investigated the expression and activity of liver cytochrome P450s (CYPs) and praziquantel (PZQ) kinetics in mice infected with Schistosoma mansoni. Swiss Webster (SW) mice of both genders were infected (100 cercariae) on postnatal day 10 and killed on post-infection days (PIDs) 30 or 55. Non-infected mice of the same age and sex served as controls. Regardless of mouse sex, infection depressed the activities of CYP1A [ethoxy/methoxy-resorufin-O-dealkylases (EROD/MROD)], 2B9/10 [pentoxy/benzyloxy-resorufin-O-dealkylases (PROD, BROD)], 2E1 [p-nitrophenol-hydroxylase (PNPH)] and 3A11 [erythromycin N-demethylase (END)] on PID 55 but not on PID 30. On PID 55, infection decreased liver CYP mRNA levels (real-time reverse transcription-polymerase chain reaction). On PID 30, whereas mRNA levels remained unaltered in males, they were depressed in females. Plasma PZQ (200 and 400 mg/kg body weight intraperitoneally) levels were measured (high-performance liquid chromatography) at different post-treatment intervals. In males and females, infection delayed the PZQ clearance on PID 55, but not on PID 30. Therefore, it can be concluded that schistosomiasis down-modulated CYP expression and activity and delayed PZQ clearance on PID 55, when a great number of parasite eggs were lodged in the liver. On PID 30, when egg-laying was initiated by the worms, no change of CYP expression and activity was found, except for a depression of CYP1A2 and 3A11 mRNAs in female mice.

The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice / O efeito das propriedades antioxidantes do extrato aquoso do alho e da Nigella sativa como agentes anti-esquistossômicos no camundongo

The aim of this study was to assess the antioxidant and anti-schistosomal activities of the garlic extract (AGE) and Nigella sativa oil (NSO) on normal and Schistosoma mansoni-infected mice. AGE (125 mg kg-1, i.p.) and NSO (0.2 mg kg-1, i.p.) were administrated separately or in combination for successive 28 days, starting from the 1st day post infection (pi). All mice were sacrificed at weeks 7 pi. Hematological and biochemical parameters including liver and kidney functions were measured to assess the progress of anemia, and the possibility of the tissue damage. Serum total protein level, albumin, globulin and cholesterol were also determined. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the liver tissues as biomarkers for oxidative and reducing status, respectively. The possible effect of the treatment regimens on Schistosoma worms was evaluated by recording percentage of the recovered worms, tissue egg and oogram pattern. Result showed that, protection with AGE and NSO prevented most of the hematological and biochemical changes and markedly improved the antioxidant capacity of schistosomiasis mice compared to the infected-untreated ones. In addition, remarkable reduction in worms, tissue eggs and alteration in oogram pattern were recorded in all the treated groups. The antioxidant and antischistosomal action of AGE and NSO was greatly diverse according to treatment regimens. These data point to these compounds as promising agents to complement schistosomiasis specific treatment.

O propósito deste estudo foi verificar os efeitos anti-oxidantes e anti-esquistossômicos do extrato de alho (AGE) e do óleo da Nigella sativa (NSO) em camundongos normais e infectados com S. mansoni. AGE (125 mg/kg, i.p. ) e NSO (0,2 mg/kg, i.p.) foram administrados separadamente ou em combinação por 28 dias sucessivos começando do primeiro dia pós infecção (p.i.). Todos os camundongos foram sacrificados sete semanas p.i. Parâmetros hematológicos e bioquímicos incluindo funções renais e hepáticas foram medidos para avaliar o progresso da anemia e a possibilidade de dano tecidual. O nível total de proteínas séricas, albumina, globulina e colesterol foram também medidos. Níveis de malondialdeído (MDA) e glutationa (GSH) foram determinados em tecido hepático como biomarcações para o estado oxidativo e redutor, respectivamente. O possível efeito dos tratamentos sobre os vermes de Schistosoma foram avaliados através do percentual de vermes recuperados, ovos no tecido e o oograma. Resultados mostraram que a proteção com AGE e NSO preveniu a maior parte das alterações hematológicas e bioquímicas e melhoraram bastante a capacidade anti-oxidante de camundongos com esquistossomose comparados com aqueles infectados e não tratados. Adicionalmente, foi registrado uma acentuada redução nos vermes, ovos no tecido e alterações do oograma. A ação anti-oxidante e anti-esquistossômica do AGE e NSO foi diferente de acordo com os vários tratamentos. Estes dados mostram que estes compostos são agentes promissores para complementar o tratamento específico da esquistossomose.

Activity of liver microsomal enzymes during the chronic phase of murine schistosomiasis

The effects of schistosomiasis on microsomal enzymes were studied on post-infection day 90 when accumulated damage and fibrosis are most intense but granulomatous reaction around the eggs harbored in the liver is smaller than during the earlier phases. Swiss Webster (SW) and DBA/2 mice of either sex (N = 12 per sex per group) were infected with 100 Schistosoma mansoni cercariae on postnatal day 10 and killed on post-infection day 90. Cytochrome P-450 (CYP) concentration and alkoxyresorufin-O-dealkylases (EROD, MROD, BROD, and PROD), p-nitrophenol-hydroxylase (PNPH), coumarin-7-hydroxylase (COH), and UDP-glucuronosyltransferase (UGT) activities were measured in hepatic microsomes. Age-matched mice of the same sex and strain were used as controls. In S. mansoni-infected mice, CYP1A- and 2B-mediated activities (control = 100 percent) were reduced in SW (EROD: male (M) 36 percent, female (F) 38 percent; MROD: M 38 percent, F 39 percent; BROD: M 46 percent, F 19 percent; PROD: M 50 percent, F 28 percent) and DBA/2 mice (EROD: M 64 percent, F 58 percent; MROD: M 60 percent; BROD: F 49 percent; PROD: M 73 percent) while PNPH (CYP2E1) was decreased in SW (M 31 percent, F 38 percent) but not in DBA/2 mice. COH did not differ between infected and control DBA/2 and UGT, a phase-2 enzyme, was not altered by infection. In conclusion, chronic S. mansoni infection reduced total CYP content and all CYP-mediated activities evaluated in SW mice, including those catalyzed by CYP2E1 (PNPH), CYP1A (EROD, MROD) and 2B (BROD, PROD). In DBA/2 mice, however, CYP2A5- and 2E1-mediated activities remained unchanged while total CYP content and activities mediated by other CYP isoforms were depressed during chronic schistosomiasis.

Efficacy of Citrus reticulata and Mirazid in treatment of Schistosoma mansoni

This work has been carried out to investigate the effect of Schistosoma mansoni infection on mice livers after treatment with the ethanolic extract of Citrus reticulata root or the oleo-resin extract from Myrrh of Commiphora molmol tree (Mirazid), as a new antishistosomal drug. Marker enzymes for different cell organelles were measured; succinate dehydrogenase (SDH); lactate dehydrogenase (LDH) and its isoenzymes; glucose-6-phosphatase (G-6-Pase); acid phosphatase (AP) and 5'- nucleotidase. Liver function enzymes; aspartate aminotransferase (AST); alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were also estimated. Parasitological studies through ova count and worm burden will also be taken into consideration. The results showed a marked reduction in SDH, LDH, AST, and ALT enzyme activities and a significant increase in G-6-Pase, AP, 5'- nucleotidase, and ALP after S. mansoni infection. A noticeable alteration in LDH subunits were also noticed. Treatment with C. reticulata or Mirazid improved all the previous enzyme activities with a noticeable reduction in ova count and worm burden.

Effect of schistosoma mansoni infection on kidney sodium potassium adenosine triphosphatase activity in experimental

Schistosoma mansoni is a common parasite in Egypt. Disturbance in renal function is a striking complication of bilharzial infection. ATPase enzyme is considered to be responsible for the generation of energy supply for the extrusion of Na[+] exchange for K[+] and maintence of water and electrolyte balance. In this study Na [+] K[+] ATPase activities have been assayed in kindeys of healthy and Schistosoma mansoni - infected mice before and after treatment with praziquantel. Schistosoma mansoni infection caused significant decrease of the kidney Na[+] - K[+] ATPase activities which were reversed by treatment of mice with praziquantel [200 mg/kg B. Wt. for three doses in 24 hours]. Possible explanations of these findings are clarified

Aspectos imunologicos do sistema enzimatico fenoloxidase de Schistosoma mansoni / Immunological aspects of the phenol oxidase enzymatic system of Schistosoma mansoni

O sistema enzimatico fenoloxidase (EC1.10.3.1, EC1.10.3.2) esta amplamente distribuido entre os seres vivos, tendo sido descrito em diferentes especies do reino animal e vegetal. Apesar de desempenhar um papel fundamental na formacao da capsula ou parede dos ovos de trematodeos, o sistema enzimatico fenoloxidase (PO) tem sido pouco estudado nesses organismos. No presente trabalho sao apresentados os resultados iniciais de imunizacoes de coelhos contra PO de femeas adultas de S. mansoni e tirosinase de cogumelo (Sigma). As analises imunologicas, realizadas atraves de imunodifusao dupla (teste de Ouchterlony) e imunoeletroforese, revelaram identidade imunitaria parcial entre PO de machos e femeas....

Bioquímica da esquistossomose mansônica: envolvimento dos siderossomos nos processos inflamatórios hepáticos / Biochemistry of schistosomiasis mansoni: involvement of siderosomes in hepatic inflammatory processes

Os processos inflamatórios que se desenvolvem durante as etapas avançadas da esquistossomose mansônica foram relacionados, com o acúmulo de siderossomos, a capacidade dos ions ferrosos/férricos de desencadearem a formaçäo de radicais livres e a peroxidaçäo de lipídios membranáceos, assim como à diminuiçäo da estabilidade das membranas dos diversos componentes do comportamento lisossômico hepático. Os lisossomos isolados de figados de camundongos infectados por 100 cercárias, com 80 e 100 dias de infecçäo, foram respectivamente, 2,5 e quase 4 vezes mais frágeis que os controles, isolados de figados de camundongos näo infectados. A presença de siderossomos em grande quantidade foi demonstrada por espectrometria aos raios-X

Atividade dissacaridásica intestinal da esquistossomose mansônica: estudo evolutivo em camundongos com diferentes cargas de infestaçäo / Intestinal activity of disaccharides in schistosomiasis mansoni: study of the course in mice with different loads of infestation

A esquistossomose mansônica compromete vários órgäos, sendo o intestino e o fígado os mais agredidos. Com a intençäo de verificar o comprometimento do intestino delgado, dependente da intensidade e do tempo de infecçäo pelo Schistosoma mansoni, analisou-se a atividade das dissacaridases - lactase, sacarase e maltase - em 112 camundongos, distribuídos em 3 grupos: grupo I - controle, grupo II - infestado com 30 cercárias, grupo III - infestado com 60 cercárias. Observou-se uma diminuiçäo da atividade lactásica, sacarásica e maltásica do intestino delgado, decorrente da infestaçäo esquistossomótica, do tempo de infestaçäo e da alteraçäo entre ambos. O íleo é o segmento que demonstrou maior sensibilidade a esquistossomose, tendo uma diminuiçäo das suas dissacaridases a partir da fase inicial de infestaçäo. Opostamente, o jejuno só mais tardiamente mostra essas alteraçöes, exceto em relaçäo a lactase. Detectou-se um aumento da atividade dissacaridásica, inclusive para a lactase, em todos os grupos, com a evoluçäo etária dos animais, quantitativamente menor nos infestados. Cargas de 30 e 60 cercárias devem ser consideradas do mesmo porte, pois produziram reduçäo semelhante na atividade dissacaridásica