ABSTRACT Purpose To develop a model of induction of type-2 diabetes (DM2) by combining low doses of streptozotocin (STZ) and a cafeteria diet. Methods Forty male Wistar rats (200 g) were allocated into four groups: control (non-diabetic, n = 10); STZ 30 mg/kg (diabetic, n = 10); STZ 35 mg/kg (diabetic,n = 10); and STZ 40 mg/kg (diabetic, n = 10). DM2 was induced with a single intraperitoneal injection of STZ after four weeks of cafeteria diet in the three diabetic groups. All animals were evaluated as for anthropometric, and biochemical analyses, as well as liver, kidney and pancreas histological analyses. Results Lower weight gain, higher water intake, higher Lee index, hyperglycemia and modified total protein, urea, alpha-amylase, as well as insulin resistance, hepatic steatosis, pancreas, and kidney injury were observed in animals treated with 35 and 40 mg/kg of STZ. Conclusions The results show that the experimental model using cafeteria diet associated with 35 mg/kg of STZ is a low-cost model and efficient in order to develop DM2, confirmed by the presence of polydipsia, hyperglycemia, altered biochemical tests, insulin resistance and damages to the liver, pancreas and kidney, which is similar to the disease found in humans.

Abstract Lichens have exhibited numerous biological activities, including growth inhibition of tumor cells. This study evaluated the antiproliferative activity of hypostictic and salazinic acids against tumor cell lines (B16-F10, PC-03, MCF7, HT-29, HEP-G2, K562 and 786-0) by the SRB assay in vitro and antitumor activity in experimental murine melanoma in vivo. Activation of caspase-3 was quantified by flow cytometry. The murine experimental melanoma model B16-F10 was used in BALB/c mice for evaluation of antitumor activity. Hypostictic acid showed significant antiproliferative activity in K562 cells (GI50 2.20 µM), B16-F10 (GI50 13.78 µM) and 786-0 (GI50 14.24 µM), whereas salazinic acid was more active against K562 cells (GI50 64.36 µM), HT-29 (GI50 67.91 µM) and B16-F10 (GI5078.64 µM). Quantification of capase-3 revealed that the test compounds did not increase the expression of that enzyme. In the in vivo antitumor evaluation in B16-F10 melanoma, the isolated compounds inhibited tumor growth in relation to weight and volume. Hypostictic acid (16.7 mg/kg) inhibited 72% and salazinic acid 88% of tumor volume (p < 0.05). The results indicated that, both in the in vitro and in vivo models, the compounds evaluated showed antiproliferative and antitumor activities.