Saccharomyces Boulardii alleviates neuroinflammation and oxidative stress in PTZ-kindled seizure rat model

Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1625-1635. doi: 10.1007/s00210-024-03361-8. Epub 2024 Aug 14.

Abstract

Previous research have reported that modulating the gut microbiome composition by fecal microbiota transplantation and probiotic administration can alleviate seizure occurrence and severity. Saccharomyces boulardii (SB) is a yeast probiotic that has demonstrated ameliorating effects on anxiety, memory and cognitive deficit, and brain amyloidogenesis. In this research, our goal was to examine the anti-seizure effects of SB on the pentylenetetrazole (PTZ)-kindled male Wistar rats. The animals were randomly categorized into four test groups. The rats were orally administered with saline (control and PTZ groups) or S. boulardii (SB + PTZ and SB groups) for 57 days. From the 29th day of the experiment, the animals received intraperitoneally saline (control and SB groups) or PTZ (PTZ and SB + PTZ groups) on alternate days for 30 days. The administration dose of SB and PTZ was 1010 CFU/ml/day and 35 mg/kg, respectively. We assessed animal seizure behavior, neuroinflammation, oxidative stress, and the levels of matrix metalloproteinase-9 (MMP-9) and brain-derived neurotrophic factor (BDNF) in the hippocampus tissue. S. boulardii hindered the PTZ-induced kindling development. SB treatment elevated glutathione (GSH) and total antioxidant capacity (TAC) and reduced malondialdehyde (MDA) levels. SB also lessened the hippocampal levels of BDNF and MMP-9. Following SB supplementation, proinflammatory cytokines interleukin-1 beta (IL-1β) and IL-6 were lowered, and anti-inflammatory cytokine IL-10 was enhanced. Overall, our data indicated, for the first time, the positive impact of SB on the PTZ-kindled seizure rat model. The anti-seizure activity of SB was mediated by modulating oxidative stress, neuroinflammation, and MMP-9 and BDNF levels.

Keywords: Saccharomyces boulardii; BDNF; Neuroinflammation; Oxidative stress; Pentylenetetrazol; Seizure.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Kindling, Neurologic / drug effects
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Neuroinflammatory Diseases* / chemically induced
  • Neuroinflammatory Diseases* / metabolism
  • Oxidative Stress* / drug effects
  • Pentylenetetrazole
  • Probiotics* / administration & dosage
  • Probiotics* / pharmacology
  • Rats
  • Rats, Wistar
  • Saccharomyces boulardii*
  • Seizures* / chemically induced
  • Seizures* / drug therapy
  • Seizures* / metabolism

Substances

  • Pentylenetetrazole
  • Brain-Derived Neurotrophic Factor
  • Matrix Metalloproteinase 9
  • Bdnf protein, rat
  • Mmp9 protein, rat
  • Cytokines