Maryam Jafar Sameri - Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran & Physiology department, Abadan University of Medical Sciences, Abadan, Iran.
Rafie Belali - Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Niloofar Neisi - Infectious and Tropical Diseases Research Center, Health Research Institute, Department of Medical virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Reza Noei Razliqi * - Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Seyed Ali Mard - Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Feryal Savari - Department of basic sciences, Shoushtar Faculty of Medical Sciences, Shoushtar, Iran.
Seyyed Saeed Azandeh - Department of Anatomical Sciences, School of Medicine, Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Liver diseases and injuries are important medical problems worldwide. Acute liver failure (ALF) is a clinical syndrome characterized by severe functional impairment and widespread death of hepatocytes. Liver transplantation is the only treatment available so far. Exosomes are nanovesicles originating from intracellular organelles. They regulate the cellular and molecular mechanisms of their recipient cells and have promising potential for clinical application in acute and chronic liver injuries. This study compares the effect of Sodium hydrosulfide (NaHS) modified exosomes with non-modified exosomes in CCL۴-induced acute liver injury to ascertain their role in ameliorating hepatic injury. Methods: Human Mesenchymal stem cells (MSCs) were treated with or without NaHS (۱ μmol) and exosomes were isolated using an exosome isolation kit. Male mice (۸-۱۲ weeks old) were randomly divided into four groups (n=۶): ۱-control, ۲-PBS, ۳- MSC-Exo, and ۴- H۲S-Exo. Animals received ۲.۸ ml/kg body weight of CCL۴ solution intraperitoneally, and ۲۴ h later MSC-Exo (non-modified), H۲S-Exo (NaHS-modified), or PBS, was injected in the tail vein. Moreover, ۲۴ h after Exo administration, mice were sacrificed for tissue and blood collection. Results: Administration of both MSC-Exo and H۲S-Exo reduced inflammatory cytokines (IL-۶, TNF-α), total oxidant levels, liver aminotransferases, and cellular apoptosis. Conclusions: MSC-Exo and H۲S-Exo had hepato-protective effects against CCL۴-induced liver injury in mice. Modification of cell culture medium with NaHS as an H۲S donor enhances the therapeutic effects of MSC exosomes.

Acute liver failure (ALF), CCL۴-induced liver injury, Exosomes, Mesenchymal stem cells (MSCs), Sodium hydrosulfide (NaHS).