RESUMEN
OBJECTIVE: The aim of the present study was to reveal the possible effect of sulforaphane on oxidative stress and inflammation in rats liver with toxic hepatitis induced by acetaminophene. BACKGROUND: Sulforaphane is a compound with high antioxidant properties. Acetaminophen, which is a para-aminophenol derivative, can lead to fatal hepatic necrosis with direct hepatotoxic effects at high doses. METHODS: Thirty six male Sprague-Dawley rats were randomly divided into four groups. Control group (n = 9) was fed with standard rat chow and water for 3 days. Group APAP (n = 9) received a single dose acetaminophen 1 g/kg by oral gavage in addition to standard chow and water. Group SFN (n = 9) received sulforaphane 500 µg/kg by oral gavage in addition to standard chow and water for 3 days. Group APAP+SFN (n = 9) received sulforaphane 500 µg/kg and a single dose acetaminophen 1 g/kg by oral gavage in addition to standard chow and water. Acetaminophen was administered three hours after SFN administration. RESULTS: Neopterin, MDA, AST, ALT and CRP levels of group APAP were significantly increased compared to control group. GSH level of group APAP was significantly lower than in the control group. CONCLUSION: Sulforaphane is a protective agent against acetaminophen-induced liver damage and it can be added in the treatment protocol (Tab. 1, Fig. 5, Ref. 51).
Asunto(s)
Acetaminofén/toxicidad , Analgésicos no Narcóticos/toxicidad , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Isotiocianatos/farmacología , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Alanina Transaminasa/efectos de los fármacos , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/efectos de los fármacos , Aspartato Aminotransferasas/metabolismo , Proteína C-Reactiva/efectos de los fármacos , Proteína C-Reactiva/metabolismo , Inflamación , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Neopterin/metabolismo , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Ratas , Ratas Sprague-Dawley , SulfóxidosRESUMEN
The plasma disposition of fenbendazole (FBZ), oxfendazole (OFZ) and albendazole (ABZ); and the enantiospecific disposition of OFZ, and ABZSO produced were investigated following an oral administration (50 mg/kg) in dogs. Blood samples were collected from 1 to 120 h post-administration. The plasma samples were analysed by high performance liquid chromatography (HPLC). The plasma concentration of FBZ, OFZ, ABZ and their metabolites were significantly different from each other and depended on the drug administered. The sulphone metabolite (FBZSO2) of FBZ was not detected in any plasma samples and the parent molecule ABZ did not reach quantifiable concentrations following FBZ and ABZ administration, respectively. OFZ and its sulphone metabolite attained a significantly higher plasma concentration and remained much longer in plasma compared with FBZ and ABZ and their respective metabolites. The maximum plasma concentrations (Cmax), area under the concentration time curve (AUC) and mean residence time (MRT) of parent OFZ were more than 30, 68 and 2 times those of FBZ, respectively. The same parameters for ABZSO were also significantly greater than those of FBZSO. The ratio for total AUCs of both the parent drug and the metabolites were 1:42:7 for following FBZ, OFZ and ABZ administration, respectively. The enantiomers were never in racemic proportions and (+) enantiomers of both OFZ and ABZSO were predominant in plasma. The AUC of (+) enantiomers of OFZ and ABZSO was, respectively more than three and seven times larger than that of (-) enantiomers of both molecules. It is concluded that the plasma concentration of OFZ was substantially greater compared with FBZ and ABZ. The data on the pharmacokinetic profile of OFZ presented here may contribute to evaluate its potential as an anthelmintic drug for parasite control in dogs.
Asunto(s)
Albendazol/farmacocinética , Antihelmínticos/farmacocinética , Bencimidazoles/farmacocinética , Perros/metabolismo , Fenbendazol/farmacocinética , Administración Oral , Albendazol/administración & dosificación , Albendazol/química , Animales , Antihelmínticos/administración & dosificación , Antihelmínticos/sangre , Antihelmínticos/química , Área Bajo la Curva , Bencimidazoles/administración & dosificación , Bencimidazoles/química , Cromatografía Líquida de Alta Presión/veterinaria , Fenbendazol/administración & dosificación , Fenbendazol/química , Reproducibilidad de los ResultadosRESUMEN
A comparative chromatographic study was developed for the simultaneous quantitative resolution of trimethoprim (TMP) and sulphamethoxazole (SMX) in veterinary formulations. Multi-wavelength chromatograms were recorded by using diode array detector (DAD) system at the five-wavelength set consisting of 220, 230, 240, 250 and 260 nm. In the first step, five different calibration equations at the above wavelengths for each drug were obtained by using the relationship between concentration and peak area. These calibration graphs were used for the quantitative evaluation of TMP and SMX in samples. These single-wavelength applications were called traditional LC method. In the second step, principal component regression (PCR) and partial least-squares (PLS) calibrations were applied to the above mentioned multi-wavelength chromatograms. The amount of two investigated drugs in samples was determined by the constructed PCR and PLS calibrations. The experimental results obtained from each single-wavelength calibration graph were compared with those obtained by the chemometric approaches and chromatographic multivariate approaches give successful results more than traditional LC method.