ABSTRACT
The increasing prevalence of diabetes mellitus in the world is of great concern. As synthetic drugs have undesirable side effects or contraindications, traditional medicinal plants are being used for treatments of diabetes. This study aimed to determine the protective effect of aloe vera [AV] on beta cells of diabetic rats. Forty adult male rats were utilized and divided equally into four groups. The first served as the control group; the second was the streptozotocin [STZ] group [single intraperitoneal dose of 65 mg/kg body weight]; the third was the preventive AV group, which was given a daily oral dose of AV [300 mg/kg body weight/day] for 14 days along with a single intraperitoneal injection of STZ given after 7 days from the start of AV; the fourth group was the curative AV group, which was given a single intraperitoneal injection of STZ and after 7 days were given a daily oral dose of AV for 14 days. Pancreatic tail samples were taken 14 days after the treatment with AV. Paraffin sections were prepared for histological and immunohistochemical studies. The results revealed that a single dose of STZ induced marked cytoplasmic vacuolations and pyknotic nuclei in many islet cells. The AV preventive group showed normal-appearing islet cells. The AV curative group showed cytoplasmic vacuolations and pyknotic nuclei in many islet cells. Statistical analysis revealed a significant decrease [P<0.05] in anti-insulin antibody reaction and bcl2 expression in the diabetic group and the AV curative group compared with the control group, whereas there was an insignificant increase in the preventive group. The present study suggests that AV when used as a preventive agent can protect against STZ-induced diabetes in rats. Therefore, AV should be given to prediabetic patients and to individuals at high risk for diabetes
Subject(s)
Male , Animals, Laboratory , Aloe/adverse effects , Protective Agents , Plant Preparations , Insulin-Secreting Cells/ultrastructure , Immunohistochemistry/statistics & numerical data , Microscopy, Polarization/statistics & numerical data , RatsABSTRACT
O transplante de ilhotas microencapsuladas constitui uma alternativa terapêutica interessante para o Diabetes Mellitus tipo 1, permitindo um melhor controle glicêmico e eliminando a necessidade de imunossupressão. Entretanto, a manutenção a longo prazo da viabilidade das células-β ainda é um desafio. No isolamento, a perda da matriz extracelular e as condições hipóxicas subsequentes afetam decisivamente a sobrevivência e funcionalidade das ilhotas. Objetivo Para diminuir o estresse sobre o enxerto, levando a um sucesso prolongado do transplante, propôs-se a adição de perfluorocarbono (PFC) ou laminina (LN), moléculas associadas respectivamente à oxigenação e interações célula-célula, ao biomaterial baseado em alginato, Biodritina, adequado ao encapsulamento celular. Metodologia Para testar a estabilidade das formulações PFC-Biodritina e LN-Biodritina, microcápsulas foram submetidas a diferentes estresses (rotacional, osmótico, temperatura e cultura) por 7 e 30 dias. A pureza do biomaterial foi avaliada pela coincubação com macrófagos murinos RAW264.7, por 3, 9 e 24h, quando a ativação dos macrófagos foi observada pela expressão gênica de IL- 1β e TNFα. Microcápsulas implantadas i.p. em camundongos foram recuperadas após 7 ou 30 dias, para análises de biocompatibilidade. A expressão de níveis de mRNA (bax, bad, bcl-2, bcl-XL, xiap, caspase 3, mcp1/ccl2, hsp70, ldh, insulina 1 e 2), proteínas (Bax, Bcl-XL e Xiap) e a atividade de Caspase3 foram avaliadas em ilhotas microencapsuladas com PFC- e LN-Biodritina, após cultura de 48h em condições de normóxia e hipóxia (<2% O2). Camundongos diabéticos foram transplantados com ilhotas encapsuladas nas diferentes formulações e os animais foram monitorados pelas variações de massa corporal, glicêmicas e pela funcionalidade do enxerto (TOTGs). As ilhotas foram recuperadas de animais normo ou hiperglicêmicos e uma análise de biocompatibilidade das cápsulas foi realizada, assim como a avaliação funcional das células-β...
Transplantation of microencapsulated islets represents an attractive therapeutical approach to treat type 1 Diabetes Mellitus, accounting for an improved glycemic control and the abolishment of immunosuppressive therapies. However, maintenance of long-term β-cell viability remains a major problem. During islet isolation, the loss of extracellular matrix interactions and the hypoxic conditions thereafter dramatically affect β-cell survival and function. Objective To lessen the burden of islet stress and achieve a better outcome in islet transplantation we tested the addition of perfluorocarbon (PFC) or laminin (LN), molecules associated respectively with oxygenation and cell-cell interaction, to Biodritin, an alginate-based material suitable for cell microencapsulation. Methodology To test the stability of PFC-Biodritin and LN-Biodritin composites, microcapsules were subjected to different stresses (rotational, osmotic, temperature and culture) for 7 and 30 days. To assess biomaterial purity microcapsules were co-incubated with RAW264.7 murine macrophage cell line for 3, 9 and 24h and macrophage activation was detected through mRNA levels of IL-1β and TNFα. Microcapsules were implanted i.p. in mice and retrieved after 7 or 30 days, for biocompatibility analyses. Gene expression at mRNA (bax, bad, bcl-2, bcl-XL, xiap, caspase 3, mcp1/ccl2, hsp70, ldh, insulin 1 and 2) and protein (Bax, Bcl-XL and Xiap) levels, together with Caspase3 activity, were evaluated in islets microencapsulated in PFC- or LN-Biodritin, upon culturing for 48h in normoxic or hypoxic (<2% O2) conditions. Diabetic mice were transplanted with PFC- or LN-Biodritin microencapsulated islets, followed by assessments of body weight, glycemia and graft function by oral glucose tolerance tests (OGTTs). Microencapsulated islets were retrieved from normoglycemic or hyperglycemic mice and biocompatibility analyses of the beads together with a functional assessment of the graft followed. After graft...