Melissa Officinalis L. aqueous extract pretreatment decreases methotrexate-induced hepatotoxicity at lower dose and increases 99mTc-phytate liver uptake, as a probe of liver toxicity assessment, in rats.

OBJECTIVE: 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 of Melissa officinalis (M. officinalis), the aqueous extract of this plant was evaluated to ameliorate MTX-associated hepatotoxicity in rats. METHODS: Adult female Wistar rats were received or not M. officinalis aqueous extract at doses of 100 mg/kg (for 14 and 24 consecutive days) and 2 g/kg (for 14 consecutive days) by gavage technique. MTX (20 mg/kg) was intraperitoneally injected on the 10th- and 20th-day post-M. officinalis treatment. 24 h after the last day of treatment, 99mTc-phytate was intravenously injected through the tail of rats. Animals were killed at 20 min 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. RESULT: A significant increase in liver radioactivity was detected in M. officinalis+MTX receiving groups compared with the MTX rats which were more robust at a dose of 100 mg/kg for 14 days. Also, a significant reduction in liver radioactivity was evident with M. officinalis extract at a dose of 2 g/kg for 14 days in comparison with the control group, this reduction was not significant at the lower dose of 100 mg/kg. Gamma scintigraphy and histopathological examinations confirmed the hepatoprotective effect of M. officinalis vs MTX-induced liver injury in rats. CONCLUSION: 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 (100 mg/kg for 14 days) ameliorates the MTX-associated hepatotoxicity in rats; however, M. officinalis itself induces liver toxicity at higher doses.

St. John's Wort accelerates the liver clearance of technetium-99-sestamibi in rats.

BACKGROUND: The intense liver uptake of technetium-99-sestamibi (Tc-MIBI) and photon scattering from the liver cause problems in quantitative perfusion interpretation. Hence, Tc-MIBI is a substrate for P-glycoprotein pump; variations in P-glycoprotein levels may affect liver clearance. METHODS AND RESULTS: Adult female Wistar rats were divided into seven main groups [control and St. John's Wort (SJW) treated] and each SJW-treated group included three subgroups that were killed at 15, 30, and 45 min after Tc-MIBI injection. Treated groups received an SJW extract suspension at two doses of 100 and 400 mg/kg once daily for 5, 10, and 14 days, respectively. Tc-MIBI was injected intravenously to all rats 24 h after the final treatment. The rats were anesthetized at the mentioned time after tracer injection, and heart and liver tissues were removed, weighed, and their radioactivity was counted. One rat from each group was selected randomly for myocardial perfusion imaging. A significant increase in liver clearance and heart-to-liver ratio was observed in all SJW-treated groups compared with the control, especially at 10 days after SJW treatment. The heart radioactivity decreased in SJW-receiving groups at 14 days after SJW treatment. CONCLUSION: This study showed that SJW extract accelerates the liver clearance of Tc-MIBI and significantly reduces photon scattering from the liver.