Toxicological effects and pharmacokinetics of rosemary (Rosmarinus officinalis) extract in common carp (Cyprinus carpio)

Rosemary (Rosmarinus officinalis) is a new therapeutic agent against streptococcosis and monogenean infections in fish. However, the toxicity of rosemary and the kinetics of one of its major component (1,8-Cineole) are unclear. In the present study, liver, kidney and intestine histopathology, plasma chemistry, kinetics of 1,8-Cineole in blood and mucus were examined in common carp fed a diet containing rosemary extract. Feeding the fish >= 20 ml aqueous extract/100 g feed caused nuclear pyknosis and cell atrophy in the liver. Fish fed >= 40 ml aqueous extract/100 g developed pyknotic cells with cytoplasmic vacuoles in the kidney, leading to tubular necrosis. Feeding the fish the rosemary diet for 10 and 20 days increased plasma aspartate aminotransferase levels, a sign of liver damage. Following oral administration of 80 ml aqueous extract/100 g feed, the 1,8-Cineole blood level peaked at 60 min at 117.9 +/- 3.5 ng/ml. The elimination half-life (T-1/2) of 1,8-Cineole in the blood was 248 min. In mucus, the levels of 1,8-Cineole at the end of 5, 10 and 20 days were 1.5 +/- 0.8 ng, 5 +/- 4.1 ng and 6.1 +/- 3.8 ng per mg crude dried mucus, respectively. These results suggest that at high doses, rosemary aqueous extract diets can cause liver and kidney damage in common carp. Further studies are needed to establish a suitable dosage for oral treatment of parasitic diseases.