Abstract
Hepatotoxicity remains amongst the restricting factors of Methotrexate (MTX)-associated cancer therapy, especially in high doses of chemo-drugs or prolonged treatment. Due to the known protective effects ofMelissa officinalis(M. officinalis), the aqueous extract of this plant was evaluated to ameliorate MTX-associated hepatotoxicity in rats. Adult female Wistar rats were received or notM. officinalisaqueous extract at doses of 100mg/kg (for 14 and 24 consecutive days) and 2g/kg (for 14 consecutive days) by gavage technique. MTX (20mg/kg) was intraperitoneally injected on the 10th- and 20th-day post-M.officinalistreatment. 24h after the last day of treatment, 99mTc-phytate was intravenously injected through the tail of rats. Animals were killed at 20min after radiocolloid injection, and vital tissues including the liver and spleen were isolated, weighed, and their radioactivity was counted. As well, 99mTc-phytate scintigraphy and histopathology of the liver were performed for higher accuracy. A significant increase in liver radioactivity was detected inM. officinalis+MTX receiving groups compared with the MTX rats which were more robust at a dose of 100mg/kg for 14days. Also, a significant reduction in liver radioactivity was evident withM. officinalisextract at a dose of 2g/kg for 14days in comparison with the control group, this reduction was not significant at the lower dose of 100mg/kg. Gamma scintigraphy and histopathological examinations confirmed the hepatoprotective effect ofM. officinalisvs MTX-induced liver injury in rats. In conclusion, we highlighted the liver uptake of 99mTc-phytate as a valuable method for assessment of liver toxicity and addressed that M. officinalis pretreatment (100mg/kg for 14days) ameliorates the MTX-associated hepatotoxicity in rats; however, M. officinalis itself induces liver toxicity at higher doses.
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