DNA-Free Recombinant SV40 Capsids Protect Mice from Acute Renal Failure by Inducing Stress Response, Survival Pathway and Apoptotic Arrest

Viruses induce signaling and host defense during infection. Employing these natural trigger mechanisms to combat organ or tissue failure is hampered by harmful effects of most viruses. Here we demonstrate that SV40 empty capsids (Virus Like Particles-VLPs), with no DNA, induce host Hsp/c70 and Akt-1 survival pathways, key players in cellular survival mechanisms. We postulated that this signaling might protect against organ damage in vivo. Acute kidney injury (AKI) was chosen as target. AKI is critical, prevalent disorder in humans, caused by nephrotoxic agents, sepsis or ischemia, via apoptosis/necrosis of renal tubular cells, with high morbidity and mortality. Systemic administration of VLPs activated Akt-1 and upregulated Hsp/c70 in vivo. Experiments in mercury-induced AKI mouse model demonstrated that apoptosis, oxidative stress and toxic renal failure were significantly attenuated by pretreatment with capsids prior to the mercury insult. Survival rate increased from 12% to >60%, with wide dose response. This study demonstrates that SV40 VLPs, devoid of DNA, may potentially be used as prophylactic agent for AKI. We anticipate that these finding may be projected to a wide range of organ failure, using empty capsids of SV40 as well as other viruses

Antioxidant and antibacterial activity of extracts, fractions and isolated substances from the flowers of Acacia podalyriifolia A. Cunn. ex G. Don

The extracts and fractions from the flowers of A. podalyriifolia were analyzed previously for antibacterial activity using diffusion in disk, Antioxidant properties were evaluated by determining radical scavenging power (DPPH test) and total phenol content was measured (Folin method). The present study describes the in vitro antibacterial (determining minimum inhibitory concentration) and antioxidant activities (by thiobarbituric acid reactive species - TBARS method) for the ethanol extract, dichloromethane and ethyl acetate fractions and two flavanones (naringenin and 5-β-D-glycosyl-naringenin) isolated from the flowers of Acacia podalyriifolia A. Cunn. ex G. Don. The flavanones naringenin and 5-β-D-glycosyl-naringenin had not previously been obtained from this species. The most effective antibacterial activity was observed in the ethyl acetate fraction (MIC=0.25 mg mL-1 against Staphylococcus aureus ATCC 6538, MIC = 0.125 mg mL-1 against Staphylococcus epidermidis ATCC 12229, MIC=0.5 mg mL-1 against Streptococcus pyogenes ATCC 19615, Klebsiella pneumoniae ATCC 13883 and Proteus mirabilis ATCC 43071). The evaluated samples showed antioxidant activity on the TBARS test, especially for ethanol extract (1000 ppm), which was the most active (29.43% ± 0.65) followed by ethyl acetate fraction (1000 ppm, 24.84% ± 1,28), both demonstrating higher activity than that presented by ascorbic acid (1000 ppm, 21.73% ± 1.77), although lower than the BHT (1000 ppm 35.15% ± 3.42), both reference compounds. Naringenin and 5-β-D-glycosyl-naringenin demonstrated antioxidant action, but only naringenin inhibited the growth of gram-positive and gram-negative bacteria.Os extratos e frações de Acacia podalyriifolia foram analisados previamente para a atividade antibacteriana através da difusão em disco e as propriedades antioxidantes foram verificadas pela determinação da capacidade removedora do radical livre DPPH e pela mensuração do conteúdo de fenólicos totais (Método de Folin). O presente estudo descreve as atividades antibacteriana (determinação da concentração inibitória mínima) e antioxidante (espécies reativas do ácido tiobarbitúrico - teste TBARS) para o extrato etanólico e as frações diclorometano e acetato de etila e para duas flavanonas (naringenina e 5-β-D-glicosil-naringenina) isoladas das flores de Acacia podalyriifolia A. Cunn. ex G. Don. As flavanonas naringenina e 5-β-D-glicosil-naringenina ainda não haviam sido obtidas desta espécie. A atividade antibacteriana mais efetiva foi observada com a fração acetato de etila (CIM=0,25 mg/mL contra Staphylococcus aureus ATCC 6538; CIM=0,125 mg/mL, contra Staphylococcus epidermidis ATCC 12229; CIM=0,5 mg/mL contra Streptococcus pyogenes ATCC 19615, Klebsiella pneumoniae ATCC 13883 e Proteus mirabilis ATCC 43071). As amostras avaliadas demonstraram atividade pelo teste TBARS, especialmente o extrato etanólico (1000 ppm), que foi o mais ativo (29,43% ± 0.65), seguido pela fração acetato de etila (1000 ppm, 24,84% ± 1,28), ambos demonstrando atividade mais elevada que a apresentada pelo ácido ascórbico (1000 ppm, 21,73% ± 1,77), ainda que menor que a do BHT (1000 ppm, 35,15% ± 3,42), ambas substâncias de referência. Naringenina e 5-β-D-glicosil-naringenina demonstraram ação antioxidante, porém somente a naringenina inibiu o crescimento de bactérias gram-positivas e gram-negativas