Changes in Hepatic Phase-I and -II Drug-metabolizing Enzymes and Antioxidant Capacity in Egyptian Ovine Fascioliasis Treated with Triclabendazole (original) (raw)
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Molecular and Biochemical Parasitology, 2013
Fasciolasis is a zoonotic parasitic disease caused by Fasciola hepatica and its control is mainly based on the use of triclabendazole (TCBZ). Parasite resistance to different anthelmintics is growing worldwide, including the resistance of F. hepatica to TCBZ. In the present work we evaluate "in vivo" the activity of xenobiotic metabolizing enzymes of phase I (carboxyl esterases) and phase II (glutathione S-transferases and carbonyl reductases) recovered of flukes from sheep treated with TCBZ. All three enzymes showed increased activity in TCBZ flukes returning 60 h post-treatment at similar to baseline unexposed flukes. TCBZ action may induce secondary oxidative stress, which may explain the observed increment in activities of the analyzed enzymes as a defensive mechanism. The enzymes analyzed are candidates to participate actively in the development of resistance at TCBZ in F. hepatica.
Pharmacological Research Communications, 1981
The effects of experimental infection with Fasciola hepatica on the in vitro drug-metabolizing activity of the hepatic mixed function oxidase (MFO) system have been studied in the rat. Decreases in cytochrome P-450-dependent metabolizing activities (p-nitroanisole O-demethylase, aminopyrine N-demethylase, hexobarbital oxidase, aniline hydroxylase and zoxazolamine hydroxylase) are observed throughout the infection period and are maximal in t~e acute stage. The decreases are consequent to decreased cytochrome P-450 and NADPH-cytochrome P-450 (cytochrome c) reductase. The depressed drug-metabolizing ability of the liver monooxygenase system might alter the steroids and fatty acids catabolism in the liver cell and decrease the safety margin for those flukicidal agents that are detoxified by the monooxyoenase pathway.
Pharmacological Research, 1989
Fascioliasis causes a dramatic decrease in drug-metabolizing ability of the hepatic monooxygenase (MFO) and glucuronosyltransferase (GT) enzyme systems in the rat. The present study was undertaken to determine whether lipid peroxidation is involved in the enzymatic loss. Peroxidative damage of membrane lipids (as assessed by the tissue content of malonic dialdehyde, MDA, and the diene conjugation absorption in microsomal membranes) was found to occur over the entire course of the liver infection (concomitant to a decrease in glutathione levels), and to different degrees in relation to the various steps of the parasite cycle. The onset (MDA six times the controls ; AE 1%=1. 55 at the 20th day) coincides with the beginning of the loss of MFO (-30%) and GT (-20% at the 20th day), and peaks between the 30th and 40th day (MDA eight times the controls ; AE 1 % = 1-96), when the loss in the enzyme activities is maximal (MFO-60/70% ; GT-65/95%). There was a strict correlation at all the observation times between the extent of lipid peroxidation and the decrease in drug metabolizing ability : this supports the view that lipid peroxidation is the major agent in the impairment of MFO and GT enzyme activities, and very likely in the initiation of the pathological degeneration of the liver tissue. As evidenced by histological examination, the phagocytic response of the liver tissue to the parasite invasion and growth leads to oxidative stress, which is the causative agent in the initiation and development of lipid peroxidation. KEY WORDS: experimental fascioliasis, impairment of hepatic phase I and phase II drugmetabolizing enzymes, lipid peroxidation, phagocytic response .
Serum enzymes and hepatic changes in sheep infested with Fasciola hepatica
Fasciola hepatica, also known as sheep liver fluke is a parasitic flatworm of the class Trematoda, phylum Platyhelminthes that infects liver of various mammals, including humans. Fasciolosis is a parasitic disease of sheep caused by Fasciola hepatica. It has a worldwide distribution and it causes significant morbidity, mortality, liver damage and loss of weight. This study provides evidence for the presence of the parasite in the liver of sheep and biochemical values for 26 sheep samples which have been infested naturally from Fasciola hepatica parasite. Infestation was perceived throughout liver's macroscopic examination in slaughterhouses and microscopic examination too. From 224 sheep examined, 26 of them resulted infested by Fasciola hepatica. Biochemical indicators analysed in this study are alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase and lactate dehydrogenase. Results have shown different values compared with the references but significantly higher changes have resulted in lactate dehydrogenase values (842.26U/I).
Circulating oxidative stress status in desert sheep naturally infected with Fasciola hepatica
Veterinary Parasitology, 2008
Oxidative stress is a general mechanism whereby free radicals induce oxidative damages and reduce the antioxidant defences of the biological systems. The aim of the present study was to determine plasma malondialdehyde levels as a biomarker of lipid peroxidation and its relation to the antioxidants status (plasma ascorbate and blood glutathione concentrations), liver function tests and anaemia in spontaneous ovine fascioliasis. For this purpose, jugular blood samples and livers of 27 infected ewes with Fasciola hepatica along with blood samples of 20 healthy (control) ewes were collected from animals slaughtered in a F. hepatica endemic area (Kharga oasis, Egypt). An increase (P < 0.001) in plasma malondialdehyde (141.1%) accompanied by decreased levels (P < 0.001) of albumin (29.3%) and ascorbate (36.2%) in plasma and glutathione in blood (31.6%) of infected sheep was noticed when compared with control values. In the infected group, malondialdehyde values were positively correlated with liver fluke burden (r = 0.57, P = 0.002) and the activity of plasma aspartate aminotransferase (r = 0.39, P = 0.0.046) and g-glutamyltransferase (r = 0.64, P = 0.0003) and negatively correlated with the concentrations of albumin (r = À0.53, P = 0.004), ascorbate (r = À0.46, P = 0.0.17) and glutathione (r = À0.41, P = 0.034). In conclusion, oxidative stress is a significant feature of chronic F. hepatica infection in grazing sheep. #
In the present work, we evaluate in vivo the activity of carboxylesterase of Fasciola hepatica exposed to triclabendazole. We observed a statistically significant increase in enzyme activity at 24 and 48 h post treatment (P < 0.01 and P < 0.001, respectively). The zymogram of cytosolic fractions identified a protein of 170 kDa containing the carboxylesterase activity. The densitograms of the zymograms confirmed the phenomenon of enzyme induction under the experimental conditions of the assay. These results provide not only the understanding of the importance of this metabolic pathway in flukes but carboxylesterase would also be an enzyme that could participate more actively in the development of anthelmintic resistance at TCBZ.
International Journal of Veterinary Science, 2023
Fasciola hepatica, a parasitic trematode, affects cattle and many mammals, including humans. The present study was carried out in Assuit governate, Egypt, over one year from 2018 to 2019, to assess the prevalence of fascioliasis in cattle and sheep. We clinically examined 835 animals (303 cattle and 532 sheep) from different private farms. We performed the fecal examination through a direct smear and did a sedimentation technique. The results demonstrated that fascioliasis was present in 20.8% of cattle and 17.1% of sheep, and the overall prevalence was 18.4%. After assessing associated risk factors, there was a significant association only between sex and infection rate (P<0.05). Other assessed risk factors (species, water, and feeding source) did not affect the infection level (P>0.05). By calculating the odds ratio, the sex was considered as a risk factor as odds ratio (OR) =5.879, 95% confidence interval (CI) 3.699-9.449. Categorized the animals into six groups. We treated each group with either albendazole, triclabendazole, superzole, clorsulon, or rafoxanide. NC group received no treatment. Animals were subjected to clinical and laboratory examination after the second dose's third and sixth week. The recovery percentage in animals treated with albendazole, triclabendazole, and Superzole was 84%, while 84% and 96% in animals treated with clorsulon and rafoxanide, respectively. All the drugs were effective (P<0.05); nonetheless, rafoxanide demonstrated the best recovery percentage (area under curve =0.605 in cattle and =0.615 in sheep).
Journal of Medical Microbiology and Infectious Diseases, 2015
Introduction: To determine an indicator for Triclabendazole (TCBZ) efficacy, Alanine aminotransferase (ALT) activity in Fasciola hepatica (Iranian isolate) parasite in presence and absence of TCBZ was evaluated by an in vitro cultivation method. Also, ALT enzyme activity between none and parasitized-infected sheep liver tissues was assessed. Method: The sheep livers were collected and transferred immediately to the Department of Parasitology. Adult living parasites were recovered, washed and divided into two groups, treatment and control groups with 10 parasites in each. We added 15 μg TCBZ to the treatment group; then incubated both groups for 4 h at 37ºC. The parasites, infected and parasite free liver tissues were ground and homogenized by a Mortar and pestle, centrifuged, and supernatants were recovered. Protein concentration and ALT enzyme activity were measured in the supenatants. Results: The results of ALT enzyme activity assay showed 0.03 U/ml/mg protein for treated F. hepatica and 0.01 U/ml/mg protein for untreated samples, the mean values of difference was not significant (p>0.05). The difference between ALT activity in none and parasitized-infected liver was not significant (p>0.05). However, two-sample T-test analysis showed higher ALT activity in treated and untreated parasite in comparison with none and parasitized-infected liver specimens (p<0.05). In addition to ALT protein band for parasite and liver tissue, Cathepsin enzyme (proteases) was detected for parasite by SDS-PAGE analysis. Conclusion: ALT activity cannot be considered as a useful marker for TCBZ efficacy in F. hepatica treatment. However, ALT enzyme showed comparable activities in parasite and its host liver tissue.