Crocin Prevents Sub-Cellular Organelle Damage, Proteolysis and Apoptosis in Rat Hepatocytes: A Justification for Its Hepatoprotection

Authors

Bahareh Sadat Yousefsani Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Hossein Hosseinzadeh Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Jalal Pourahmad Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Soghra Mehri Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract:

Crocin, the main constituent of saffron (Crocus sativus L.), is a natural carotenoid which is known for its antioxidant activity. Liver as the organ that metabolizes many chemicals is one of the first position that is at risk of environmental pollutants. It is clear that compounds that exhibit antioxidant properties, scavenging of free radicals and inhibition of lipid peroxidation are expected to show hepatoprotective effects. Previous studies have proven the protective effect of crocin on the liver. The aim of this study is to find out the exact hepatoprotective mechanisms of this compound. In the present study, the protective effects of various concentrations of crocin (5, 10, 25, 50 and 100 μg/mL) were examined against oxidative stress toxicity induced by cumene hydroperoxide (CHP) on isolated rat hepatocytes. To find out the exact protective activity of crocin, we evaluated cell lysis, lipid peroxidation, reactive oxygen species (ROS) generation, GSH/GSSG, collapse of mitochondrial membrane potential, lysosomal membrane damage, the release of cytochrome c, and cellular proteolysis. Crocin (50 and 100 µg/mL) reduces cell lysis, lipid peroxidation, ROS generation, collapse of mitochondrial membrane potential, lysosomal membrane damage, cytochrome c release, and cellular proteolysis. It also increase GSH/GSSG. Crocin (50 and 100 µg/mL) reduced liver toxicity not only as an antioxidant but also by protecting the mitochondria and lysosome. Our data demonstrated that crocin is a promising candidate for preventing liver injury associated with oxidative stress. These findings pave the way to further studies evaluating the clinical protective effect of crocin.

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