The use of 99mTc-phytate for assessment the protective effect of vitamin E against hepatotoxicity induced by methotrexat in rat

Abstract

Hepatotoxicity is one of the most common side effects of methotrexate (MTX) therapy in patients. The aim of this study was to evaluate the protective effect of vitamin E against MTX-induced hepatotoxicity using 99m Tc-phytate as a radiopharmaceutical agent in animals. Rats were divided into five groups as follows: control, solvent, Vit E (100 mg/kg), MTX (20 mg/kg) and Vit E + MTX. Animals were intraperitoneally injected with Vit E for 17 days before MTX injection and continued for 4 days. Tc-phytate was injected into the tail of rats after the 21 days of Vit E administration. Percentage of the injected dose per gram of liver and spleen tissues (%ID/g) was calculated in treated rats. Liver imaging was obtained with gamma camera. In other experiment, liver of treated rats was assessed for histopathology. Tc-phytate uptake (%ID/g) of livers in control, solvent, Vit E, MTX and Vit E + MTX groups were 8.99% ± 1.37, 8.53% ± 2.91, 8.65% ± 3.84, 3.22% ± 1.09 and 8.38% ± 2.68. Vit E administration resulted in a significant increase of the level of %ID/g in MTX-injected animal. Vit E pre-treatment improved the shape of liver in MTX-treated rat which was seen abnormal view in planar imaging. Histophatological examinations approved the protective effect of Vit E against MTX-induced hepatotoxicity in rats. The results of this study show that Vit E significantly attenuates the MTX-induced hepatotoxicity in rats, and 99m Tc-phytate is an acceptable radiopharmaceutical agent for assessment of liver and spleen damages in the animal model.

The Protective Effects of Nutraceutical Components in Methotrexate-Induced Toxicity Models—An Overview

“…In rat model of MTX-induced liver injury therapeutic delivery of β-carotene, an important source of vitamin A in the human diet, with antioxidant properties, led to decreased hepatic MDA activity and increased hepatic SOD, CAT and GSH peroxidase activities under conditions of [ 153 ]. Amirfakhrian et al [ 177 ] showed the protective effect of vitamin E on liver architecture assessed by 99mTc-phytate functional imaging. Ismail et al [ 178 ] report that while thiamine pyrophosphate exhibited protective effects against MTX hepatotoxicity, thiamine alone was ineffective.…”

The role of resveratrol in hepatotoxicity caused by methotrexate

“…Despite of wide usage, Mtx has a range of side effects such as hepatotoxicity -nephrotoxicity (4,(6)(7)(8)(9). Therefore, it has been advised to prevent Mtx induced hepatotoxicity, it is using concomitant with antioxidants (10).…”