title: Carbonic anhydrase enzyme as a potential therapeutic target for experimental trichinellosis.
abstract: Trichinellosis is a globally distributed helminthic infection. There is a considerable interest in developing new anti-helminthic drugs affecting all the developmental stages of Trichinella. Acetazolamide (carbonic anhydrase (CA) inhibitor) involves a novel mechanism of action by inhibiting such an essential enzyme for parasite metabolism. This work aimed to study the effect of acetazolamide against different stages of T. spiralis in experimental animals. Mice were divided into three groups: group I: infected and treated with acetazolamide on day 2 post infection (P.I.), group II: infected and treated with acetazolamide on day 12 P.I., and group III: infected non-treated. From each group, small intestine and muscles were removed for histopathological and immunohistochemical studies. Also, total adult and muscle larval count were estimated. We found that acetazolamide was effective in reduction of both adult and muscle larval counts. When given early, the effect was more pronounced on the adults (62.7 %). However, the efficacy of the drug against muscle larvae was increased when given late (63 %). Improvement of the intestinal histopathological changes was observed in all the treated groups. Degeneration of encysted larvae with minimal pathologic changes of infected skeletal muscle was observed in the treated groups. Expression of matrix metalloproteinase-9 showed a statistically significant decrease in the intestinal and muscle tissues in all treated groups as compared to the control group. In conclusion, the present study revealed that acetazolamide, carbonic anhydrase inhibitor, could be a promising drug against both adults and larvae of T. spiralis.
authors.affiliation: Department of Medical Parasitology, Faculty of Medicine, Tanta University, Tanta, Gharbiya, Egypt. abero2020@yahoo.com.
authors.forename: Abeer E
authors.initials: AE
authors.lastname: Saad
authors.affiliation: Department of Medical Parasitology, Faculty of Medicine, Tanta University, Tanta, Gharbiya, Egypt.
authors.forename: Dalia S
authors.initials: DS
authors.lastname: Ashour
authors.affiliation: Department of Medical Parasitology, Faculty of Medicine, Tanta University, Tanta, Gharbiya, Egypt.
authors.forename: Dina M
authors.initials: DM
authors.lastname: Abou Rayia
authors.affiliation: Department of Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Asmaa E
authors.initials: AE
authors.lastname: Bedeer
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015801:Helminth Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007421:Intestine, Small / Q000469:parasitology / Q000473:pathology; D007814:Larva / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000469:parasitology / Q000473:pathology; D014234:Trichinella / Q000187:drug effects / Q000201:enzymology*; D017160:Trichinella spiralis / Q000187:drug effects / Q000201:enzymology; D014235:Trichinellosis / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D015801:Helminth Proteins; D002256:Carbonic Anhydrases; D000086:Acetazolamide
keywords: Acetazolamide; Carbonic anhydrase enzyme; Matrix metalloproteinases; Trichinella spiralis