Possible Protective Effect of Co-administration of Hydrogen Sulfide and Exosomes versus Hydrogen Sulfide Preconditioned Exosomes on Hepatic Ischemia Reperfusion Injury in Adult Male Rat Model: Biochemical, Histological and Immunohistochemical Study.

Background: Liver ischemia/reperfusion (I/R) commonly happens within liver surgical
procedures as well as transplantation. It causes postoperative liver dysfunction, and poor patient
outcome. Emerging strategies assume that efficacy of mesenchymal stem cells-exosomes
(MSCs-EXOs) is dependent on status of MSCs extracellular environment. Hydrogen sulfide
(H2S) regulates several cellular signaling pathways and exerts a protective effect in various
disorders. Aim of the work: Comparing the protective influence of co-administration of H2S and
exosomes versus H2S-preconditioned exosomes on liver I/R injury adult male rat model.
Materials and Methods: Fifty adult male rats were categorized to donor, control, liver I/R,
recovery, H2S + EXOs, and H2S-preconditioned EXOs groups. At the end of experiment,
biochemical analysis [for liver enzymes, nuclear factor kappa-B (NF-κB) and superoxide
dismutase (SOD)], histological and immunohistochemical studies [for high-mobility group box 1
(HMGB1), nuclear factor-erythroid 2-related factor 2 (Nrf2), as well as heme oxygenase-1 (HO-
1)], and statistical analysis were done. Results: Ischemia/reperfusion group recorded significant
rise in hepatic enzymes, NF-κB level, HMGB1 immunoreactivity, and decrease in SOD level,
Nrf2 and HO-1 immunoreactivity. In addition to the presence of foci of disorganized hepatocytes,
necrotic cells, apoptosis, and periportal inflammatory infiltration. Recovery showed insignificant
improvement in formerly mentioned results. While the use of H2S + EXOs, or precoordinated EXOs clearly improved inflammation, antioxidant parameters, and hepatocellular
injury. Conclusion: H2S + EXOs in addition to H2S-precoordinated EXOs possessed
hepatoprotective impacts against I/R injury in the liver. Whereas H2S preconditioning of MSCs
could augment the protective impact of MSC-EXOs.