Óxido de cobre associado ao closantel em ovinos experimentalmente infectados com Haemonchus contortus: metabolismo oxidativo, hepático e imunológico

Abstract

Haemonchus contortus is the most prevalent and pathogenic parasite of sheep and the emergence of parasitic resistance to most classes of anthelmintic made the infection by this parasite one of the main obstacles to sheep rearing. Closantel is an antiparasitic that demonstrate a remarkable propensity for development of resistance to H. contortus parasite. Studies have been carried out aiming at the development of alternative means to reduce the use of anthelmintics, providing an increment in the host's immune response to the parasite or even reducing the H. contortus egg laying. In this sense, the capsule with copper oxide wire particles (COWP), which was originally developed to overcome copper deficiency in ruminants in pasture, is highlighted by its prophylactic effect in the establishment of infective larvae of H. contortus. Thus, the aim of this study was to evaluate the effect of COWP supplementation, isolated or associated with closantel, on oxidative stress markers, immune response, hematological and biochemical profile and hepatic energetic metabolism in sheep experimentally infected with H. contortus. For this, thirty Corriedale sheep, males, with approximately eight months of age and an average weight of 30 kg were used. The animals were distributed in five groups with 6 animals each: Control (negative control) consisting of healthy animals and free of parasites; HC: (positive control), consisting of animals infected by H. contortus; HC+Cu: infected with H. contortus and treated with COWP; HC+CL: infected with H. contortus and treated with closantel; HC+CL+Cu: infected with H. contortus and treated with closantel and COWP. Infected sheep were inoculated with 5,000 H. contortus larvae. The copper oxide capsule and closantel were orally supplied to the lambs. Sheep were monitored for 50 days. Blood and feces samples were collected weekly for evaluation and monitoring of parasitic infection. Animals supplemented with COWP (isolated or associated with closantel) showed a reduction in egg counts per gram of faeces as well as a reduction in adult larval counts in the abomasum, and the association of treatments was 100% effective. The treatment reduced butyrylcholinesterase (BuChE) and myeloperoxidase (MPO) activities, demonstrating that copper oxide exerts anti-inflammatory effects, in addition, prevents the inhibition of adenylate kinase (AK) and pyruvate kinase (PK) activities, maintaining the balance between consumption and production of cellular ATP. All treatments were able to reduce the levels of thiobarbituric acid reactive substances (TBARS) and increase the activity of catalase (CAT), superoxide dismutase (SOD) and the levels of glutathione (GSH) and total thiols (PSH) when compared to the infected and untreated group, better results were obtained for those supplemented with copper. COWP positively modulated the immune response in treated animals, by increasing immunoglobulins levels (IgE and IgG). There was no evidence of COWP intoxication in the treated sheep's liver and plasma copper remained low throughout the experimental period. We conclude that COWP associated with closantel is an excellent alternative for sheep producers suffering economic losses with H. contortus infection due to the multiple resistance to anthelmintic, as it resulted in a reduction of 100% in parasite count of infected lambs, also demonstrated antioxidant action and increased the immune response of sheep.