Navegando por Palavras-chave "Adriamycin"

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    Chronic supplementation of creatine and vitamins C and E increases survival and improves biochemical parameters after doxorubicin treatment in rats
    (Blackwell Publishing, 2007-12-01) Santos, Ronaldo Vagner Thomatieli dos [UNIFESP]; Batista, Miguel L.; Caperuto, Erico C.; Costa Rosa, Luis F. B. P.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Univ Mogi das Cruzes
    1. Doxorubicin is an anti-cancer drug with well-described effects against a wide range of tumours. However, doxorubicin also exhibits dose-dependent cytotoxicity. the purpose of the present study was to determine whether chronic supplementation of creatine or a mix of vitamins C and E could increase survival and improve plasma parameters 48 h after doxorubicin treatment.2. Rats were divided into four groups: (i) saline (control); (ii) doxorubicin treated; (iii) a creatine (0.2 g/kg per day)-supplemented group; and (iv) a vitamin C (250 mg/kg per day) and E (400 IU/kg per day)-supplemented group. After 30 days supplementation of rats with either creatine or the vitamins, one dose of doxorubicin (15 mg/kg, i.p.) was administered.3. There was no difference in weight loss among the groups until the 3rd day after doxorubicin treatment, but the creatine- and vitamin-supplemented groups lived longer compared with the doxorubicin only treated group (6, 7 and 3 days, respectively). the doxorubicin-treated group lost 13.4% bodyweight over 3 days, whereas the creatine- and vitamin-supplemented groups lost approximately 35% 3 days after the administration of doxorubicin. Doxorubicin treatment resulted in an increase in alanine aminotransferase (ALT; P < 0.05), lactate dehydrogenase (LDH; P < 0.05), urea (P < 0.05) and creatinine (P < 0.05) compared with levels observed in the control group. Conversely, creatine supplementation promoted a partial return to control values for LDH (P < 0.05) and creatinine (P < 0.05), whereas the vitamin mix reversed the changes in ALT (P < 0.05), LDH (P < 0.05), urea (P < 0.05) and creatinine (P < 0.05).4. in conclusion, the results of the present study indicate that the two supplementation protocols decreased the cytotoxic effects of doxorubicin and that a protective effect was more noticeable in animals supplemented with the mixture of vitamins C and E.
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    A investigação do inflamassoma NLRP3 no desenvolvimento da glomeruloesclerose segmentar e focal experimental
    (Universidade Federal de São Paulo (UNIFESP), 2020-01-30) Santos, Amandda Rakel Peixoto Dos [UNIFESP]; Silva Filho, Alvaro Pacheco E [UNIFESP]; Universidade Federal de São Paulo
    Introduction. Chronic inflammation has been associated with several diseases including chronic kidney disease (CKD), and among those, focal segmental glomerulosclerosis (FSGS), a glomerulopathy in which inflammatory and degenerative mechanisms are implicated in podocyte damage. FSGS is a disease in which 50% of the patients are resistant to corticotherapy. In the past decades, the innate immune sensor system called NLRP3 inflammasome has been widely studied, showing its important contribution to the immune response. However, little has been investigated about FSGS and NLRP3 inflammasome. Aims. As it has been observed in other diseases, we speculated that NLRP3 inflammasome may also contribute to the development of FSGS. Therefore, we have investigated NLRP3 inflammasome components in experimental FSGS in order to unravel new mechanisms of the immune responses in renal diseases. Methods. Through Adriamycin Nephropathy (DOX) in wild type mice, C57BL/6J, mutants, such as NLRP3 KO, ASC KO, CASP-1 KO, and CRE Lox transgenic mice, we evaluated and compared NLRP3 inflammasome activation. We studied renal function, as well as gene and protein expression of molecules associated with podocytopathy, inflammation and tissue repair. Results. Our data showed that NLRP3 inflammasome activation happened early, in the second day of the nephropathy model, in C57BL/6J, with increased expression of nlrp3 (p=0,0275), casp-1 (p=0,0038), pro-il-18 (p<0,0001) and serum IL-18 (p<0,0001), associated with diminished expression of genes responsible for structural podocytes proteins and slit diaphragm proteins, actn4, synpo, nphs1 and kirrel (p<0,0001), we have also found diminished numbers of podocytes, WT1 (p=0,0009), and podocyte effacement through transmission electron microscopy (TEM). Among the knockout and CRE Lox transgenic mice, we pointed out that NLRP3 KO were protected against DOX- induced injury, podocytes mainly, not showing differences in podocytes molecules expression between the groups (p>0,05), or significant changes in podocytes structure by TEM; and, although they have presented increased expression of col4a1 (p=0,0056), fsp-1 (p=0,0217) and il-33 (p=0,0132), the mmp9/timp1 ratio was decreased (p<0,0001), indicating less extracellular matrix deposit when nlrp3 is not present. Conclusions. Our results indicated that NLRP3 inflammasome participates in experimental FSGS development, specially through IL-18 and IL-33 modulation. We believe that NLRP3 inflammasome activation promotes severe podocyte damage through IL-18, but, on the other hand, without NLRP3 inflammasome, IL-33 is not inactivated by caspase-1, and without this important limiting mechanism, IL-33 induces cellular infiltration and augmented expression of pro-fibrotic molecules. Thus, NLRP3 inflammasome and FSGS relation should be deeply investigated to guide the development of drugs that act accurately, blocking podocyte damage, without compromising the surveillance of this important innate immunity component.