The effect of crocin on forgetfulness caused by cholestasis in male rats(behavioral , biochemical and genetical )

Saba Mehrabanifar,1,* Dr saeed hessami tackalou,2 Dr mohammad nasehi,3

Abstract

Introduction

Cholestasis is a condition in which the bile ducts that carry bile from the liver to the intestine to dispose, is blocked and this leads to accumulation of bile in the liver and damage to the liver. this is the case that occurs in some genetic diseases, pregnancy, metastatic cancers, gallstones, etc. because the liver is responsible for providing the required materials for brain and removes toxic substances for neurons, any damage to the liver also resulted in brain injuries. hippocampus is one of the most important part of brain that plays an essential role in memory. problems such as the occurrence of oxidative stress, mitochondrial biogenesis defects, memory impairment, etc. occur following cholestasis. crocin is active ingredient of saffron that have been proven in previous studies that has such effects, antioxidant, improvement in mitochondrial function, anti-tumor, anti-inflammatory, anti-depression, improve memory and etc. in this study, we examined the effect of crocin in behavioral, biochemical and genetic levels on amnesia induced by cholestasis.

Methods

We classified 72 wistar male rat in 9 groups including: control normal, control bdl, sham+20mg crocin, sham+30mg crocin, bdl + 15 mg crocin, bdl + 20 mg crocin, bdl + 30mg crocin. all groups were examined by y-maze’s behavioral test after the 30-day period. after the behavioral testing, killing mice and separating brain tissue (ca1 part of the hippocampus cores), activity of catalase and superoxide dismutase that both are antioxidants were measured by biochemical kits in biochemical sector and we also measured expression of tfam and pgc1a genes which have fundamental role in mitochondrial biogenesis by real-time pcr in genetic sector.

Results

After behavioral testing it was observed that 30 mg dose of crocin can significantly improve memory. after treatment with 30 mg crocin, superoxide dismutase enzyme activity had increased, but this increase was not statistically significant. but the expression of two genes tfam and pgc1a significantly (p <0.05) increased compared to the bdl group

Conclusion

Treatment with crocin at a dose of 30 mg could prevent amnesia due to cholestasis. this substance in the hippocampus section of the brain in male rats can improve the antioxidant activity of superoxide dismutase after cholestasis and probably this effect can be improved by increasing in dose. crocin improves mitochondrial biogenesis performance because the expression of two genes tfam and pgc1a that are key components of mitochondrial biogenesis significantly increased, therefore, crocin can improve mitochondrial biogenesis in hippocampus core after cholestasis.

Keywords

Cholestasis , crocin , catalase , superoxid dismutase , tfam , pgc1a