Protective effect of Morinda citrifolia L. (fruit extract) on methotrexate-induced toxicities—hematological and biochemical studies

Abstract

Methotrexate (MTX) has been widely used as an anticancer drug. It acts as a folic acid analog, inhibits purine and pyrimidine synthesis, which accounts for its efficacy in the therapy of cancer as well as for some of its toxicities. The present study is an attempt of modulating MTX-induced toxicities using aqueous extract of Morinda citrifolia L. (Noni) as a nutritional supplement. Hematological parameters such as RBC, WBC, and platelet count that decreased (p < 0.05) after methotrexate injection was found to have been restored in rats co-treated with Noni. Enhanced levels of lipid peroxides (p < 0.05) in animals administered with MTX showed significant revision after co-administration of Noni. Alterations of other biochemical constituents in blood like glucose, urea, uric acid, and cholesterol (p < 0.05) were also reversed to near normal levels in animals co-treated with Morinda citrifolia L. The study provides preliminary evidence that Morinda citrifolia L. extract can ameliorate MTX mediated side effects.

Keywords:

• methotrexate toxicity
• Morinda citrifolia L.
• Noni

Public Interest Statement

Methotrexate (MTX) (4-amino-10-methylpteroylglutamic acid) is a potent antineoplastic agent used to treat choriocarcinoma, leukemia, osteosarcoma, non-Hodgkins lymphoma, breast cancer, and lung cancer. It is also involved in the treatment of non-cancerous conditions such as rheumatoid arthritis, psoriasis, immunological abnormalities, and systemic inflammation. Low-moderate to high doses of MTX causes various side effects and may lead to conditions such as liver cirrhosis or fibrosis. It has also been shown that MTX administration has severe side effects on the hematopoietic system. This work is to highlight the importance of Morinda citrifolia L. fruit extract supplementation as an antioxidant in chemotherapy to re-establish the levels of antioxidant and to strike a balance between the oxidant and antioxidant levels thus preventing the enormous toxicity observed due to this drug. Combinational chemotherapy gives an insight for an effective treatment to cancer patients helping them exhibit minimum levels of the deleterious drug-induced side effects.

Competing Interests

The authors declare no competing interest.

Additional information

Notes on contributors

Bhakti A. Mhatre

Bhakti A. Mhatre is presently perusing PhD in Biotechnology from School of Biotechnology and Bioinformatics, D.Y. Patil University CBD Belapur, Navi Mumbai, Maharashtra, India. Mhatre is presently working on anticancer properties of Morinda citrifolia L. fruit extract. The use of chemotherapeutic agents in the treatment of cancer has hampered and complicated by toxic side effects. Many types of chemotherapy destroy cancer cells by generating free radicals which can cause cellular damage. Unfortunately, these free radicals are not discriminatory in their destructive action leading to undesirable side effects and sometimes even new cancers. Therefore, administration of antioxidants might reduce the side effects of camptothecin without compromising its efficacy. Further studies assessing the potential usefulness of Morinda citrifolia L. fruit extract treatment in methotrexate-induced toxicities on other organs and organ systems are warranted which may provide an effective way to improve their therapeutic efficacy.