Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway.

CONTEXT: Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects. OBJECTIVE: To investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat model of MGN. MATERIALS AND METHODS: Fourty male Sprague-Dawley rats were randomized into four groups. The MGN model was established and treated with a DG dose (10 mg/kg) and a positive control (TPCA1, 10 mg/kg), while normal control and MGN groups received distilled water by gavage for four consecutive weeks. At the end of the experiment, 24 h urinary protein, biochemical indices, oxidation and antioxidant levels, inflammatory parameters, histopathological examination, immunohistochemistry and immunoblotting were evaluated. RESULTS: DG significantly ameliorated kidney dysfunction by decreasing urinary protein (0.56-fold), serum creatinine (SCr) (0.78-fold), BUN (0.71-fold), TC (0.66-fold) and TG (0.73-fold) levels, and increasing ALB (1.44-fold). DG also reduced MDA (0.82-fold) and NO (0.83-fold) levels while increasing the activity of SOD (1.56-fold), CAT (1.25-fold), glutathione peroxidase (GPx) (1.55-fold) and GSH (1.81-fold). Furthermore, DG reduced Keap1 (0.76-fold) expression, Nrf2 nuclear translocation (0.79-fold), and induced NQO1 (1.25-fold) and HO-1 (1.46-fold) expression. Additionally, DG decreased IL-2 (0.55-fold), TNF-α (0.80-fold) and IL-6 (0.75-fold) levels, and reduced protein expression of NF-κB p65 (0.80-fold), IKKß (0.93-fold), p-IKKß (0.89-fold), ICAM-1 (0.88-fold), VCAM-1 (0.91-fold), MCP-1 (0.88-fold) and E-selectin (0.87-fold), and also inhibited the nuclear translocation of NF-κB p65 (0.64-fold). DISCUSSION AND CONCLUSIONS: The results suggest a potential therapeutic benefit of DG against MGN due to the inhibition of the NF-κB pathway, supporting the need for further clinical trials.

Produção in vitro de embriões bovinos em meio SOF e com SVE ou BSA / Bovine in vitro embryo production in modified SOF medium with ECS or BSA

O objetivo deste trabalho foi determinar as taxas de desenvolvimento de embriões bovinos produzidos in vitro em meio SOF suplementado com soro de vaca em estro (SVE) ou albumina sérica bovina (BSA). Os oócitos foram obtidos a partir de ovários de vacas de abatedouro e maturados in vitro (MIV) durante 24 horas em TCM199 acrescidos de 10% de SVE, estradiol (1 mg/mL), FSH (0,5 mg/mL) e hCG (0,03 UI/mL). A fecundação in vitro (FIV) foi realizada durante 18 a 20 horas em meio Fert-TALP acrescido de heparina (5,56 mg/mL), hipotaurina (1,1 mg/mL) e epinefrina (0,18 mg/mL). Tanto a MIV quanto a FIV foram realizadas em estufa de cultivo a 39ºC, 100% de umidade relativa e 5% de CO2 em ar. Para o cultivo embrionário, os zigotos foram cultivados em SOF modificado, suplementado com 10% de SVE ou 0,4% de BSA, em atmosfera com 5% de CO2, 7% de O2 e 88% de N2. Os embriões foram mantidos durante 9 dias em estufa a 39ºC com 100% de umidade relativa do ar. O emprego de BSA ou SVE como fonte protéica não promoveram diferença significativa sobre as taxas de clivagem (59,0% ou 55,6%, respectivamente) e de formação de blastocisto (40,3% ou 49,0% respectivamente). Entretanto, o SVE proporcionou maior velocidade na formação dos blastocistos (p<0,01).