The analgesic drug dipyrone is used to treat side effects (including pain and fever) of cancer chemotherapeutic agents. Dipyrone is metabolized to 4-aminoantipyrine (4-AA), a PGE2-dependent blocker and inhibitor of cyclooxygenase (COX). We evaluated the genotoxic, mutagenic, apoptotic, and immunomodulatory activities of 4-AA in vivo and the effects of its combination with the antineoplastic drugs doxorubicin, cisplatin, and cyclophosphamide. 4-AA did not cause genotoxic/mutagenic damage, splenic phagocytosis, or leukocyte alterations. However, when combined with the antineoplastic agents, 4-AA decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. These results suggest that 4-AA might interfere with DNA damage-mediated chemotherapy.

No abstract

ABSTRACT. Rupture of the Achilles tendon diminishes quality of life. The gold-standard therapy is a surgical suture, but this presents complications, including wound formation and inflammation. These complications spurred evaluation of the therapeutic potential of 10435 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (4): 10434-10449 (2014) Stem cells for tendon injury treatment mesenchymal stem cells (MSCs) from adipose tissue. New Zealand rabbits were divided into 6 groups (three treatments with two time points each) evaluated at either 14 or 28 days after surgery: cross section of the Achilles tendon (CSAT); CSAT + Suture; and CSAT + MSC. A comparison between all groups at both time points showed a statistically significant increase in capillaries and in the structural organization of collagen in the healed tendon in the CSAT + Suture and CSAT + MSC groups at the 14-day assessment. Comparison between the two time points within the same group showed a statistically significant decrease in the inflammatory process and an increase in the structural organization of collagen in the CSAT and CSAT + MSC groups. A study of the genomic integrity of the cells suggested a linear correlation between an increase of injuries and culture time. Thus, MSC transplantation is a good alternative for treatment of Achilles tendon ruptures because it may be conducted without surgery and tendon suture and, therefore, has no risk of adverse effects resulting from the surgical wound or inflammation caused by nonabsorbable sutures. Furthermore, this alternative treatment exhibits a better capacity for wound healing and maintaining the original tendon architecture, depending on the arrangement of the collagen fibers, and has important therapeutic potential.

ABSTRACT. The present study investigated the effects of restricting protein and calories and supplementation of inulin, a fiber comprising a linear type of polydisperse carbohydrates composed primarily of 2423 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (1): 2422-2435 (2015) Inulin prevents cancer in malnourished animals fructil-fructose bonds (β-(2→1), on the deficiency statuses of animals in which genomic lesion development and colorectal carcinogenesis had been induced. This experiment involved adult male Swiss mice (N = 11/group). The experimental groups were as follows: Negative Control (vehicle), Positive Control, 1,2-dimethylhydrazine (DMH), Inulin, and Associate. DMH, which promoted colorectal cancer, was administered intraperitoneally in 4 20-mg/kg body weight (bw) doses during a 2-week period; inulin was administered orally at a daily dose of 50 mg/kg bw. Each group was bifurcated; half of each group was fed a normal protein diet and the other half was fed a low-protein diet. The results indicated that a correlation existed between malnutrition and an increased frequency of genomic lesions but that malnutrition did not predispose animals to colorectal cancer development. Inulin exhibited genotoxic activity, which requires further investigation, and low antigenotoxic activity. Moreover, inulin reduced the levels of intestinal carcinogenesis biomarkers in both malnourished and healthy animals. These data suggest that inulin holds therapeutic potential and is a strong candidate for inclusion among the functional foods used for cancer prevention in both properly nourished and malnourished individuals.

ABSTRACT. The use of mesenchymal stem cells (MSCs) in experimental, clinical, and therapeutic trials has grown in recent years. However, the issue remains of whether these procedures are completely safe for transplant patients. Therefore, this study was designed and carried out with the aim of evaluating two different comet assay protocols for genomic damage pattern analysis in MSCs derived from adipose tissue. The analyzed and interpreted results suggest that genetic testing is needed to support clonal expansion safety in cell therapy procedures with MSCs. Furthermore, they also suggest that if the comet assay technique would be used as a genomic integrity screening assay, the protocol performed at pH = 12 (that yielded a frequency of damaged cells: tail intensity = 9.50 ± 0.60, tail moment = 0.0122 ± 0.0007; results are reported as means ± standard deviation) would be indicated as genomic damage, and that subsequent single-strand breaks occur at pH > 13 (frequency of damaged cells: tail intensity = 30.71 ± 4.23, tail moment = 0.0447 ± 0.0073). Our study demonstrates that, in the era of regenerative medicine, it is necessary to standardize and establish a battery of tests in order to identify genomic damage prior to MSC transplantation.