Heated linoleic acid anilide: toxicity and relevance to toxic oil syndrome

The present study was undertaken to investigate toxic potentials of linoleic acid anilide (LAA) and heated linoleic acid anilide (HLAA) and their possible role in the etiology of toxic oil syndrome (TOS). Male Sprague-Dawley rats were given 250 mg/kg of LAA or HLAA in mineral oil through gavage, on alternate days for 2 weeks (total 7 doses). Control rats received an equal volume of vehicle only. The animals were sacrificed at day 1, 7 and 28 following the last dose. Ratio of organ weight/body weight showed a significant increase in lung in LAA group at day 7 while spleen showed remarkable increases in both treatment groups at day 1 and 7. On the other hand, this ratio showed decreases in case of liver, brain and heart at some time points. Among blood parameters, red cell counts and hemoglobin content decreased at day 1 in both LAA and HLAA treated groups, while platelet counts showed an increase. Serum LDH, GOT and GPT activities significantly decreased at day 1 and 7 in both LAA and HLAA treated groups, however, these changes were more prominent in the HLAA treated group. Interestingly, at day 28, these serum enzyme levels recovered to control levels. Both LAA and HLAA treated groups showed a decrease in serum IgM levels at day 1, however, at day 7 only the LAA group showed significant decrease. IgA levels significantly increased in both groups at all the time points studied and were more pronounced in the HLAA treated group. Similarly, IgG levels also showed increases in both the groups. In addition to serum immunoglobulin changes, alterations in the lymphocyte subpopulations were also observed. While T-cell population decreased, B-cell population remained unchanged. Among T-cell subsets, T-helper cells did not show any change while T-suppressor cells decreased significantly at day 1 in the LAA group and at day 1 and 7 in the HLAA group, but regained control levels at day 28. The biochemical and immunological alterations observed in this study as a result of LAA and HLAA exposure and more so by HLAA further support that the fatty acid anilides may play a role in the etiology of TOS.