Systemic versus local injection of bone marrow mesenchymal stem cells on 5-fluorouracil treated parotid glands of albino rats

Abstract

Objective: Head and neck cancer is the sixth leading cancer by incidence worldwide and eighth by death. Recent reports revealed that, not only radiotherapy but also chemotherapy may induce xerostomia. The aim of this study was to compare the possible regenerative effect of BMSCs through systemic and local injections. Material and Methods: 52 male Albino rats were randomly divided into 4 groups: Group 1: 10 rats received 0.5 ml of PBS by injection. Group 2: 14 rats received an intraperitoneal injection of 5-FU drug. Group 3: 14 rats were injected the same dose of 5-FU then received an intraglandular transplantation of BMSCs suspended in 0.5 ml of PBS at day 1 after 5-FU administration. Group 4: 14 rats were injected the same dose of 5-FU then received an intravenous injection of BMSCs suspended in 0.5 ml of PBS via the tail vein at day 1 after 5-FU administration. Results: Histological examination showed that group 2 showed features of severe degenerative changes which increased over time. Group 3 showed increasing amelioration in the ductal structure overtime. Group 4 also showed regenerated ductal elements however concerning apoptotic changes, immunohistochemistry results revealed improvement in both group 3 and 4 over group 2 with no statistical difference between groups 3 and 4. Conclusion: Histological and immunohistochemical features in group 3 and group 4 revealed similar amelioration in regenerative potentials. On the other hand, regenerative features of both experimental groups were statistically significant as compared independently to group 1. KEYWORDS 5-fluourouracil; anti-caspase-3; BMSCs; H&E; parotid salivary gland. RESUMOObjetivo: O carcinoma de cabeça e pescoço é o sexto câncer de maior incidência no mundo sendo a oitava causa de morte por cancer. Relatos recentes revelaram que não apenas a radioterapia, mas também a quimioterapia podem induzir xerostomia. O objetivo desse estudo foi comparar a possivel ação regenerative de BMSCs através de injeção local e sistêmica. Material e Métodos: 52 ratos Albino foram aleatoriamente alocados em 4 grupos: Grupo 1: 10 ratos que receberam 0.5 ml de injeção de PBS. Grupo 2: 14 ratos que receberam injeção intraperitoneal da droga 5-FU. Grupo 3: 14 ratos que foram injetados com a mesma dose de 5-FU e receberam transplante intraglandular de BMSCs ressuspendidas em 0.5mL de PBS no dia 1 após a administração do 5-FU. Grupo 4: 14 ratos que foram injetados com a mesma dose de 5-FU e receberam injeção intravenosa de BMSCs ressuspendidas em 0.5mL de PBS via veia caudal 1 dia após a administração de 5-FU. Resultados: O exame histológico demonstrou que o grupo 2 apresentou alterações degenerativas severas que se agravaram com o tempo. O Grupo 3 mostrou melhora da estrutura ductal ao longo do experimento. Group 4 também mostrou elementos ductais regenerados. Referente a alterações apoptóticas,análise imunohistoquimica mostrou melhora nos grupos 3 e 4 comparados ao grupo 2, sendo que os grupos 3 e 4 foram estatisticamente semelhantes. Conclusão: Análises histológicas e imun...

The Effect of Bone Marrow Derived Mesenchymal Stem Cells in Ameliorating Cytarabine-Induced Injury in The Submandibular Salivary Glands of Rats

“…The blood vessels showed dilatation and congestion with red blood cells. These results coincide with the results of previous studies that showed the effects of Cytarabine, 5-fluorouracil, and Cisplatin drugs on the submandibular salivary glands of rats (6), (11), (12) .…”

“…This period was chosen according to a previous comparative study that compared the therapeutic effect of systemically injected BMMSCs on the side effects of 5-Fluorouracil (chemotherapeutic drug) on the parotid glands after six and ten days. The statistical analysis showed a non-significant difference between the two groups with a p-value>0.05 (p-value=0.280) (11) .…”

Effects of chemo-therapeutic drugs used in head and neck cancers on sub-mandibular glands of rats

“…Martin et al [44] stated that 5-FU affects DNA, RNA, and protein synthesis, and inhibits the secretion mechanism of the cells in the pancreas. Enlargement in aci- [2] in a histological and immunohistochemical study reported that 5-FU administration showed features of severe degenerative changes in parotid glands of the rats, which increased over time. 5-FU administration showed ill-defined acinar outline, multiple different sized vacuolization, and disfigured nuclear pattern.…”