Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuvant-induced arthritis and hematological indices in rats.

Sir,

We have read the article “Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuvant-induced arthritis and hematological indices in rats” by Banji et al.[1] published in Indian Journal of Pharmacology with great interest. The methodology of the study has the following flaws which we would wish to state:

Hypothesis of the study was a beneficial role of combination of curcumin and methotrexate (MTX) to hematological toxicity produced by MTX. It is stated that MTX cause the impairment in the hematological indices with the dose of 2 mg/kg in group IV. In group V, MTX (1 mg/kg) + curcumin (30 mg/kg) and in group VI, MTX (1 mg/kg) + curcumin (100 mg/kg) showed the improvement in hematological indices. It is difficult to understand the comparison of hematological toxicity produced by methotrexate 2 mg/ kg and the combination of methotrexate 1 mg/kg and curcumin. Hematological toxicity of MTX is dose dependent. Higher dose of MTX is more prone to cause hematological abnormalities like pancytopenia, while lower dose are more prone to cause megaloblastic anemia.[2] In the present study, the doses of MTX in groups V and VI are 50% less than those in group IV. We can assume that toxicity reduction in groups V and VI is not purely related to addition of curcumin. To nullify this bias, either author should have had one more group of MTX with dose of 1 mg/kg or dose of MTX should have been kept 2 mg/kg with curcumin.

In this study, the authors have not mentioned the vehicle in which the curcumin was dissolved. The vehicle control group was of normal saline, so we can assume that curcumin was dissolved in normal saline. Curcumin is relatively insoluble in water, but dissolves in acetone, gum acacia, ethyl acetate, methanol, ethanol, n-butanol, isopropanol, hexane and dichloromethane.[34] Is curcumin soluble in normal saline?

Paw volume measured on various days in all the study groups is mentioned in [Table 1] by Banji et al.[1] We want to mention that paw volume on day 0 (baseline data) should also be presented in Table 1. The authors stated that the time course of arthritis after the administration of Freund's complete adjuvant showed swelling of hind paw from the ninth day. Paw volume on the ninth day is almost similar in all the groups and without baseline data it is difficult to show paw oedema on the ninth day. Paw volume of negative control (group 1) on the ninth day is comparable with other groups.