Evaluation of the brain tissue oxidative stress status during sepsis after mesenchymal stem cell's conditioned medium administration in male rats

In the present study, we hypothesized that conditioned medium (CM) derived from mesenchymal stem cells attenuates the brain oxidative stress in sepsis induced by the cecal ligation and puncture (CLP) model.

This study was performed in the Department of Physiology at Tehran University of Medical Sciences from August 2018 to April 2019. Conditioned medium was collected from mesenchymal stem cells isolated from ratchr('39')s adipose tissues at the second culture passage. Male Wistar rats weighting (220-250 g) were randomly divided into three experimental groups (n=8 each): Sham, Sepsis and CM. Sepsis was induced by cecal ligation and puncture model in the Sepsis and CM groups. Animals in the CM group received the conditioned medium from 5×105 mesenchymal stem cells (2 h after sepsis induction, i. p., 3-5 mL). The systolic blood pressure and O2 saturation were measured 24 h after the treatment. The plasma and brain tissue samples were taken for inflammatory and oxidative stress assessment, respectively.

Septic rats showed a significantly lower systolic blood pressure and O2 saturation level. They also had a significant increase in the plasma inflammatory indices (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and brain malondialdehyde (MDA) content as well as a significant reduction in the brain superoxide dismutase (SOD) activity compared to the Sham group. The CM group had significantly higher systolic blood pressure and O2 saturation level compared to the septic rats. The animals in the CM group showed a significant attenuation in the plasma inflammatory indices (TNF-α and IL-6) and brain MDA content while having a significantly higher brain SOD activity compared to the Sepsis group.

Our findings showed that conditioned medium derived from mesenchymal stem cells has protective effects in preventing the inflammatory and oxidative stress status and may be suggested as a promising treatment in patients suffering from sepsis and septic shock.