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1.
Curr Top Med Chem ; 19(22): 2049-2057, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31364515

RESUMEN

BACKGROUND: Scorpion venom causes renal injury and affects vascular ion-channels function. Centruroides margaritatus scorpion is found in Colombia and is frequently the cause of envenomation accidents; however, its renal impact has never been investigated. OBJECTIVE: To evaluate the effects of C. margaritatus venom (CmV) on renal parameters using isolated rat kidney and renal cell culture models. METHODS: Wistar rats (n = 5, weighing 240-300 g) were first perfused with Krebs-Henseleit solution containing 6 g 100 mL-1 bovine serum albumin. After 30 minutes, the kidneys were perfused with CmV to a final concentration of 10 µgmL-1; evaluation was performed by measuring Perfusion Pressure (PP), Renal Vascular Resistance (RVR), Urinary Flow (UF), Glomerular Filtration Rate (GFR), and percentage of electrolyte tubular transport. Moreover, kidney histological analyses and cell cytotoxicity in renal tubule epithelial cells (MDCK) and proximal tubular cells (LLC-MK2) were assessed. RESULTS: CmV increased PP and RVR 60 min after perfusion. On the other hand, UF, GFR, and the percentages of sodium, potassium and chloride tubular transport decreased after experimental envenomation. UF dropped after 120 min, while GFR and percentage of electrolyte tubular transport diminished after 60, 90 and 120 min. CmV was not toxic to MDCK cell line but reduced the viability of LLC-MK2 cells at concentrations ranging from 6.25 to 200 µgmL-1. Histological analyses disclosed hydropic degeneration, edema, and protein deposits. Flow cytometry disclosed that cell death occurred predominantly by necrosis. CONCLUSION: Our results suggest that C. margaritatus venom can trigger renal impairment, mainly in the proximal kidney tubule.


Asunto(s)
Riñón/efectos de los fármacos , Venenos de Escorpión/farmacología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Colombia , Perros , Relación Dosis-Respuesta a Droga , Riñón/patología , Células de Riñón Canino Madin Darby/efectos de los fármacos , Células de Riñón Canino Madin Darby/patología , Masculino , Ratas , Ratas Wistar , Escorpiones , Relación Estructura-Actividad
2.
Braz. j. med. biol. res ; 52(1): e7581, 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-974275

RESUMEN

Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 µg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 µg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3′,4′-OH flavonoids are known inhibitors of phospholipases A2.


Asunto(s)
Animales , Masculino , Ratas , Antivenenos/farmacología , Extractos Vegetales/farmacología , Raíces de Plantas/química , Venenos de Crotálidos/antagonistas & inhibidores , Edema/tratamiento farmacológico , Hemorragia/etiología , Antivenenos/aislamiento & purificación , Bothrops , Venenos de Crotálidos/toxicidad , Polygalaceae/química , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/etiología , Hemorragia/tratamiento farmacológico
3.
Braz J Med Biol Res ; 52(1): e7581, 2018 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-30517287

RESUMEN

Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 µg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 µg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3',4'-OH flavonoids are known inhibitors of phospholipases A2.


Asunto(s)
Antivenenos/farmacología , Venenos de Crotálidos/antagonistas & inhibidores , Edema/tratamiento farmacológico , Hemorragia/etiología , Extractos Vegetales/farmacología , Raíces de Plantas/química , Polygalaceae/química , Animales , Antivenenos/aislamiento & purificación , Bothrops , Venenos de Crotálidos/toxicidad , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/etiología , Hemorragia/tratamiento farmacológico , Masculino , Ratas
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