Abstract
Background Oral mucositis is the most debilitating and troublesome adverse effect of irinotecan (CPT-11) treatment. It adversely affects the patient quality of life. The aim of this work was to study the histological, immunohistochemical, and molecular changes in the oral mucosa by CPT-11 and the possible alleviated role of atorvastatin. Methods Rats were randomly divided into control, CPT-11-treated group, and CPT-11+ atorvastatin-treated group. At the end of the experiment, the anterior two-thirds of the tongue was dissected out and divided into two parts: one part for light microscopic examination and the second for molecular study. Results CPT-11-treated group revealed loss of normal mucosal organization, areas of ulceration and inflammation, and loss of architecture of lingual papillae. A significant decrease in immunohistochemical and molecular gene expression of Ki-67 and antiapoptotic Bcl-2 levels was observed. A significant increase in NF-κB immunohistochemical and mRNA gene expression level and a nonsignificant increase in Nrf2 gene expression were detected. Coadministration of atorvastatin showed remarkable improvement in the histopathological picture with a significant increase in Ki-67 and Bcl-2, a significant decrease in NF-κB protein and gene expression, and a significant increase in Nrf2 gene expression. Conclusion Atorvastatin substantially attenuates CPT-11-induced oral mucositis through the initiation of the antiapoptotic gene, modulation of the inflammatory, and antioxidant gene expression.
Highlights
Chemotherapy drugs are a widely used cancer treatment approach that interferes with the division of cancer cells and can be administered either alone or in combination with other modalities [1].Chemotherapy’s biggest drawback is its lack of selectivity, as it works on both tumor cells and healthy cells that proliferate quickly [2]
The hematoxylin and eosin (H&E)-stained tongue sections the control group (Figure 1(a) revealed that the dorsal surface was studded with conical-shaped filiform papillae)
Atorvastatin increases NF-κB mRNA levels, but not as much as CPT-11 (1:84 ± 0:28, P < 0:001); the coadministration of both drugs neutralized their individual effects on gene expression, which was still decreased, but above its normal levels (1:58 ± 0:23, P < 0:001; Figure 7)
Summary
Chemotherapy drugs are a widely used cancer treatment approach that interferes with the division of cancer cells and can be administered either alone or in combination with other modalities [1].Chemotherapy’s biggest drawback is its lack of selectivity, as it works on both tumor cells and healthy cells that proliferate quickly [2]. Irinotecan (CPT-11) is a camptothecin derivative and a recently developed chemotherapy drug effective against multiple malignant tumours, including colorectal, stomach, ovary, and lung cancers, as well as central nervous system tumours, including recurrent glioblastomas, rhabdomyosarcomas, and other sarcomas [5]. It inhibits topoisomerase-1, an enzyme involved in DNA replication, and causes several single-strand DNA breakdowns and cell division inhibition [6]. Oral mucositis is the most debilitating and troublesome adverse effect of irinotecan (CPT-11) treatment It adversely affects the patient quality of life. Atorvastatin substantially attenuates CPT-11-induced oral mucositis through the initiation of the antiapoptotic gene, modulation of the inflammatory, and antioxidant gene expression
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