title: Effect of clonidine in mice injected with Tityus discrepans scorpion venom.
abstract: A study was conducted to assess the effect of clonidine (α(2)-adrenoceptor selective agonist) on glycemia, serum and urine α-amylase, blood urea nitrogen (BUN), serum creatinine, white blood cell count, kidney histology and zymogen granule content in pancreatic acini, in mice under the effect of Tityus discrepans (Td) scorpion venom. BALB/c male mice (20 ± 2 g, n = 7-11) were intraperitoneally (ip) injected with a sublethal dose (1 μg/g) of Td venom, and were treated (ip) with 0.1 μg/g of clonidine (Catapresan(®)) or 0.9% NaCl 30 min after the venom injection, and then every 2 h. Six hours later, mice were anesthetized with diethylether and urine and blood samples were withdrawn by cystocentesis and cardiocentesis, respectively. Tissue samples were obtained and fixed immediately in buffered formalin (2%, pH 7.4) and then processed for stain H&E. Td venom did not cause hyperglycemia by itself. However, clonidine induced hyperglycemia, which was synergized by Td venom. Although the venom did not produce hyperamylasemia, clonidine significantly diminished serum α-amylase activity in envenomed mice. Td venom did not significantly increase urinary α-amylase activity, which was unaffected by clonidine. Morphometric analysis using microphotographs of pancreata from mice injected with Td venom showed a reduced zymogen granule content as judged by the acidophilic bidimensional area of acini. This effect was significantly reduced by clonidine. Kidney samples showed histological changes which were partially affected by the drug. Clonidine reduced the increase in BUN and serum creatinine concentration in envenomed mice. Td venom produced neutrophilia and lymphopenia, which were clonidine-resistant at the assayed dose. These results suggest that α(2)-adrenoceptor selective agonists would be able to reduce some scorpion venom-induced renal and pancreatic disturbances, possibly through the inhibition of neurotransmitter release from presynaptic cholinergic and noradrenergic terminals, as well as from adrenal medulla.
authors.affiliation: Departamento de Ciencias Biomédicas, Facultad de Ciencias Veterinarias, Universidad Central de Venezuela, Apartado 4563, Maracay 2101, Venezuela. aerg58@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez
authors.forename: H
authors.initials: H
authors.lastname: Zerpa
authors.forename: A
authors.initials: A
authors.lastname: Ruiz
authors.forename: V
authors.initials: V
authors.lastname: Bermúdez
authors.forename: F
authors.initials: F
authors.lastname: García
authors.forename: A
authors.initials: A
authors.lastname: Silva
authors.forename: L
authors.initials: L
authors.lastname: Gutiérrez
authors.forename: S
authors.initials: S
authors.lastname: Villasmil
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001806:Blood Urea Nitrogen; D003000:Clonidine / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004357:Drug Synergism; D004792:Enzyme Precursors; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced; D007091:Image Processing, Computer-Assisted; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology; D012604:Scorpion Venoms / Q000633:toxicity*; D012605:Scorpions / Q000502:physiology*; D022142:Secretory Vesicles / Q000187:drug effects / Q000648:ultrastructure; D000516:alpha-Amylases / Q000097:blood / Q000652:urine
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D004792:Enzyme Precursors; D012604:Scorpion Venoms; D003404:Creatinine; D000516:alpha-Amylases; D003000:Clonidine