Atorvastatin and trans-caryophyllene for the prevention of leukopenia in an experimental chemotherapy model in Wistar rats

Abstract

Malignant neoplasia represents the second cause of disease-related mortality and, among all patients diagnosed with cancer, 70% will receive chemotherapy during the course of treatment. As a consequence, an increasing number of researchers have focused their attention on the search for more specific anticancer therapies associated with fewer side effects. Leukopenia is an important adverse effect associated with chemotherapy. Secondary infection is very common among leukopenic patients, directly affecting the continuity of the chemotherapeutic treatment and leading to possible complications in tumor immune defense. Atorvastatin, a type of statin, is a known agent used to control hypercholesterolemia. Trans-caryophyllene, isolated from a resinous oil extracted from the copaiba tree, possesses anti-inflammatory and analgesic properties. The AIM of the present study was to evaluate, through a complete leukocyte count, the systemic immunomodulation potential of pentoxifylline (PTX), atorvastatin and trans-caryophyllene, as well as the possible prophylactic role of these drugs against secondary leukopenia, in an experimental chemotherapy model induced by 5-fluorouracil (5-FU) in wistar rats. A total of 32 male wistar rats were used, 24 of which were submitted to treatment with atorvastatin, PTX and trans-caryophyllene prior to the administration of chemotherapy. The Shapiro-Wilk test was used to verify normality and the Kruskal-Wallis test was used for negative data in the normality test. Among the drugs selected, atorvastatin exhibited the best preventive potential in regards to leukopenia secondary to experimental chemotherapy induced by 5-FU, in comparison to the group receiving saline solution, while PTX amplified such alterations in the leukograms of the animals in this trial.

Keywords: atorvastatin; chemotherapy; leukopenia; oral mucositis; trans-caryophyllene.

Figure 1.

The total leukocyte count of group I (control; animals submitted to experimental chemotherapy and treated prophylactically with saline solution) was 2,854±921.8/MM³, of group II (animals submitted to experimental chemotherapy and treated prophylactically with trans-caryophyllene), 5,688±2,284/MM³, of group III (animals submitted to experimental chemotherapy and treated prophylactically with pentoxifylline) 1,042±694.6/MM³ and of group IV (animals submitted to experimental chemotherapy and treated prophylactically with atorvastatin) 7,944±3,707/MM³. The results are expressed as mean ± standard deviation. *P<0.05; **P<0.01; ***P<0.001.