Our aim was to verify the modulative TP-4-ol capacity in 4-nitroquinoline-1-oxide induced oral rat cancer. Methods: The stereoisomers of TP-4-ol were used against the human tongue squamous cell line and the negative stereoisomer showed lower IC50. 31 Holtzman rats (120-130 grams) were cancer induced by 4-nitroquinoline-1-oxide (4-NQO/8 weeks/25 ppm) and 32 Holtzman rats (120-130 grams) were used to Healthy and TP-4-ol toxicity experiments. Six groups were used, healthy, 0.1nL/g of TP-4-ol, 8nL/g of TP-4-ol, 4-NQO, 4-NQO+0.1nL/g of TP-4-ol and 4-NQO+8nL/g of TP-4-ol. We performed the toxicity analysis by biochemical and histopathological analysis. The biochemistry analysis includes alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate transaminase [AST], Urea and Creatinine and the histopathology analysis includes the liver, kidney, lung, and spleen. Specifically, for malign modulation we performed a macroscopic and microscopic analysis. Results: The group exposed to 0.1nL/g of TP-4-ol demonstrated a reduced risk of malignancy in dysplasia considering the criteria of architecture and cytology. Similarly, a drop of percentual rats with SCC diagnosis was observed in 4-NQO+0.1nL/g (41.6%) when compared to 4-NQO (87.5%). Moreover, the 4-NQO group presented a median of 2.62 SCC/rat and the 4-NQO+0.1nL/g demonstrated a median of 0.75 SCC/rat. For toxicity analysis, 4-NQO+0.1nL/g showed focal necrosis in the kidney and 4-NQO showed lung hemorrhagic areas. Conclusion: The concentration of 0.1nL/g was more effective in reducing the tongue induction of potentially malignant and malignant lesions by 4-NQO. A kidney toxicity was observed in healthy animals exposed to 0.1nL/g of TP-4-ol.
Clinical relevance:The negative isoform of Terpinen-4-ol negatively modulates the development of potentially malignant and malignant lesions in rats (Rattus nonverdicts albinos, Holtzman) exposed to 4-NQO. (-)-Terpinen-4-ol reduced the mice percentual with squamous cell carcinoma, 87.5% to 41.6% and decreased the cancer/rat ratio of 2.62 in 4-NQO to 0.75 in 4-NQO+0.1nL/g. This represents 52.4% by group and 71.3% in the cancer/rat ratio.