Albendazole Sensitive vs. Resistant Nematodes – The Mitochondrial Ultra-Structural Changes

Studies on microtubule inhibitors have shown that the loss of equilibrium between tubulin and microtubules can generate a multitude of histochemical changes in mitochondria. This disruption of balance is also considered the basis of benzimidazole anthelmintic (BZ) activity. Studies have shown that BZ does not bond to the tubulin of the BZ-resistant Haemonchus contortus, as opposed to sensitive ones. This affinity alteration can be easily recognised by changes in the optical density and can help in the classification of H. contortus mitochondria, into sensitive (dark) and resistant (clear, unmodified zones). In order to confirm this hypothesis, we started our study from albendazole (ABZ) resistant and sensible H. contortus individuals, collected from the intestinal tract of sheep, aiming towards the identification of mitochondrial features, using the Electron Microscopy Transmission (EMT) technique. The EMT has confirmed that the structure of sensitive trichostrongilian populations was affected rapidly, only four hours after ABZ treatments. The main changes that appeared in the intestinal mitochondria of sensitive helminths were: cristae thickening and decreasing in number and cellular membrane thickening. Twelve hours after anthelmintic administration, a total blocking of metabolic functionality was observed, and finally, these changes completely altered the optical density of the mitochondria. In ABZ resistant populations, the optical density has remained normal; and the cristae number, size or functionality of resistant nematode mitochondria has remained unchanged.