Chemopreventive and chemotherapeutic activities of Dracaena cinnabari balf.f against oral cancer in vivo / Nashwan Abdullah Abdo al-Afifi

Dracaena cinnabari (DC) is a perennial tree possesses various pharmacological properties but its anticancer properties have not been clarified. Aims: To evaluate the toxicity, anticancer activity (chemopreventive and chemotherapeutic) and metastasis obstruction of the DC resin methanol extract on 4-nitroquinoline-1-oxide (4NQO)-induced oral cancer in rats. Materials and Methods: The powder of DC resin was extracted with methanol using the maceration extraction method. The toxicity profile of DC extract was investigated in Sprague Dawley (SD) rats using acute and sub-acute oral toxicity tests. In general, the chemopreventive study involves administration of 4NQO solution (cancer induction) to SD rats for 8 weeks alone or with DC extract at 100, 500 and 1000 mg/kg that started one week before the exposure until one week after the cessation of the carcinogen exposure. In the chemotherapeutic study, SD rats were given 4NQO (20 ppm) for 8 weeks followed by administration of DC extract at 100, 500 and 1000 mg/kg for another 10 weeks with or without Cisplatin (3 mg/kg I.P for every 3 weeks). All rats from both studies were sacrificed after 22 weeks, and histological analysis was performed to assess any incidence of pathological changes. Immunohistochemical expressions of selected tumour marker antibodies were analysed using an image analyser computer system, and the expression of selected genes involved in apoptosis and proliferative mechanism related to oral cancer were evaluated using RT2-PCR. Result: Acute oral toxicity revealed that the DC extract could be well tolerated up to the dose of 2000 mg/kg and at the dose of 1500 mg/kg, the sub-acute test revealed no evidence of any treatment-related changes of the animals used in this study. In the chemopreventive study, the incidence of OSCC decreased with the administration of DC extract at 100, 500 and 1000 mg/kg compared to the induced cancer and vehicle groups. In the chemotherapeutic study, there was no incidence of OSCC (0%) with the administration of DC 1000 mg/kg and Cisplatin. For both chemopreventive and chemotherapeutic studies, the survival rate increased to 100% for DC doses of 500 and 1000 mg/kg. The developed tumour was also observed to be smaller, and lymph node metastasis was inhibited in all DC treated groups with or without Cisplatin when compared to the induced cancer and vehicle groups. The DC 1000 mg/kg group inhibit the expression of Cyclin D1, Ki-67, Bcl-2 and p53 genes responsible for decreasing the transformation and the aggressiveness of the cancer tissue while a slight increase in the expression of β-catenin and E-cadherin genes that decrease the proliferation of cancer cells while maintaining epithelial polarity was observed. It was also observed that DC 1000 mg/kg induced apoptosis by upregulation of Bax and Casp3 genes and down-regulation of Tp53, Bcl-2, Cox-2, Cyclin D1 and EGFR genes when compared to the induced cancer group. Conclusion: This study provides scientific validation for the safety of DC extract up to the highest dose level used in this study. Furthermore, the data indicated that systemic administration of the DC extract has anticarcinogenic potency on oral carcinogenesis

Evaluation of obturation quality using gutta-percha and a resin-based material with different techniques / Nashwan Abdullah Abdo Al-Afifi.

Introduction: Gutta-percha (GP) has been accepted as the “gold standard” root filling material. It is the material against which most others are compared. The adhesive potential of GP to radicular dentine has been shown to be far from satisfactory. Therefore, resin-based materials that address many of the limitations of the GP/sealer combinations have been introduced. They are claimed to produce the so-called “monoblock” that is a gap-free union between core material and sealer, which adheres and penetrates into dentinal tubules. Examples of these resin-based filling materials include Resilon, EndoREZ and Guttaflow. Objectives: The objectives of this study were to evaluate and compare the obturation quality in canals obturated with a GP/AH Plus® and a resin-based material, EndoREZ® (ER) through assessments of: apical extrusion of obturation materials; percentage of canal area occupied by core filling materials versus sealer + voids; and adaptation of obturation materials to the canal walls. Materials and methods: Ninety-six mandibular premolars were randomly divided into two groups (n=48 each): GP and ER groups. Each group was further divided into 3 subgroups (n=16) according to different obturation techniques: Cold lateral compaction (CLC), warm lateral compaction (WLC) and single cone (SC). Apical extrusion was compared with Chi-square test for any association with the type of filling materials and techniques used. The teeth were subsequently embedded in resin, with one sample being selected randomly and sectioned longitudinally for scanning electron microscopy (SEM). All other samples were sectioned horizontally at 1, 3, 6 and 9 mm from the obturated canal terminus. All sections were viewed under a stereomicroscope (OLYMPUS szx7, Olympus Corp., Tokyo, Japan) at 40× magnification and micrographs were obtained. The area occupied by core filling material was determined using Cell^ D software (OLYMPUS Soft Imaging Solutions GmbH, 2008, Munster). Then, for each section, the ratio of combined area of sealer + voids to cross-sectional area of root canal was calculated. Data were analyzed using two-way repeated measure, Wilcoxon and Mann-Whitney tests. Results: There was no statistically significant difference in the incidence of material extrusion between materials and compaction techniques used. The SC group was not analysed because no extrusion was found for both materials. In CLC, the percentage of ER core filling material was significantly higher than the percentage of GP core filling material at 1 mm (P=0.005) and 3 mm (P=0.023) levels. In WLC, the percentage of ER core filling material was significantly higher than the percentage of GP core filling material at the 1 mm (P=0.029), 3 mm (P=0.006) and 9 mm (P=0.007) levels. In SC, the percentage of ER core filling materials was significantly higher than the percentage of GP core filling material at all levels: 1 mm (P=0.001), 3 mm (P=0.000), 6 mm (P=0.000) and 9 mm (P=0.000). SEM observation at different magnification showed that ER points/ER sealer seemed to suggest a better adaptation to dentine as compared to gutta-percha/AH Plus. Conclusions: The resin-based material was superior to the gutta-percha in the percentage of core filling material that occupied the canal filled area

Acute and sub-acute oral toxicity of Dracaena cinnabari resin methanol extract in rats

Abstract Background Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon’s blood, the Twobrother’s Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. Methods In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology. Results In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control. Conclusion This study demonstrates tolerability of DC resin methanol extract administered daily for 28 days up to 1500 mg/kg dose