The Effects of Different Probiotic Administration on Dexamethasone-Associated Metabolic Effects

Abstract

Glucocorticoids are steroid hormones used in clinical practice as an effective therapeutic option for their effects regarding the dysregulated immune reactions and hyperactive immune system. Their administration in the short- and long-term exposure has been associated with numerous metabolic side effects. Probiotics have been shown to modulate basal metabolism, inflammation, and oxidative stress through the regulation of composition and function of the gut microbial environment. The aim of this study was to assess the effects of Saccharomyces boulardii and Lactobacillus paracasei probiotics in dexamethasone-treated rats. The study comprised four groups, with 6 Charles River Wistar albino male rats/group; group 1 represented the negative control, rats from group 2 were administered dexamethasone, rats from group 3 were administered dexamethasone and probiotics containing the strain Saccharomyces boulardii, and rats from group 4 were administered dexamethasone and probiotics containing the strain Lactobacillus paracasei. We have assessed the plasmatic levels of glucose, total cholesterol, triglycerides, tumor necrosis factor-alpha, interleukin-10, catalase activity, and total antioxidant capacity. The administration of dexamethasone led to elevated serum concentrations of glycolipid metabolism parameters and cytokines and resulted in hepatic steatosis at the morphological level. Administration of probiotics containing Saccharomyces boulardii or Lactobacillus paracasei reduced glucose and tumor necrosis factor-alpha serum concentration in dexamethasone-treated rats. Moreover, the administration of Lactobacillus paracasei probiotics in rats that received dexamethasone increased interleukin-10 and reduced catalase activity. Regarding the liver tissue morphology, the rats that received probiotics showed improved liver histological aspects compared to the dexamethasone-treated group, suggesting that probiotics could provide positive effects regarding the metabolic and histological disturbances induced by glucocorticoids.

Keywords: dexamethasone; hepatic steatosis; hypercholesterolemia; hyperglycemia; inflammation; oxidative stress; probiotics.

Figure 1

Serum metabolic biomarkers concentration. a: p < 0.05 compared to the negative control group; b: p < 0.05 compared to the Dexa group; Abbreviations: Dexa, dexamethasone; SB, Saccharomyces boulardii; LP, Lactobacillus paracasei. The lines correspond to mean values with standard deviation.

Figure 2

Serum inflammation cytokines levels. a: p < 0.05 compared to the negative control group; b: p < 0.05 compared to the Dexa group. Abbreviations: TNF-α, tumor necrosis factor alpha; IL, interleukin; Dexa, dexamethasone; SB, Saccharomyces boulardii; LP, Lactobacillus paracasei. The lines correspond to mean values with standard deviation.

Figure 3

Catalase activity and TAC levels. a: p < 0.05 compared to the negative control group; b: p < 0.05 compared to the Dexa group. Abbreviations: TAC, total antioxidant capacity; Dexa, dexamethasone; SB, Saccharomyces boulardii; LP, Lactobacillus paracase. The lines correspond to mean values with standard deviation.

Figure 4

Rat liver sections in the study groups stained with H&E (A1,A2,B1–B3,C1–C3,D1–D3). Abbreviations: H&E, hematoxylin, and eosin. (A). Negative control group; H&E stain; (A1 20×) and (A2 40×). Normal disposition of hepatocytes within the hepatic lobule, with normal thickness of hepatic cords arranged around the central vein (CV); normal aspect of the portal space (P). (B). Dexa-treated rat group; H&E stain; (B1 20×) and (B2 40×, B3 40×). Ballooning degeneration of hepatocytes with small lipid droplets in the perinuclear area (red arrow); macrovesicular steatosis (yellow arrow); vascular congestion and inflammatory infiltrate in the central vein (); moderately dilated sinusoids with mild inflammatory infiltrate (polymorphonuclears neutrophils) within the sinusoids (blue circle); portal mixed inflammatory infiltrate (green arrow); NAS score moderate, grade 2: steatosis—grade 3; ballooning degeneration—grade 2; lobular inflammation—grade 1 (<2 foci/×20 field), portal inflammation—grade 1. (C1–C3). Dexa+ SB probiotics group; H&E stain; (C1 20×) and (C2 40×, C3 40×). Restoration of lobular architecture, with a marked reduction in macrovesicular steatosis (yellow arrow); ballooning degeneration of hepatocytes with small lipid droplets in the perinuclear area (red arrow); the portal triads exhibited moderate lymphocytic inflammatory infiltrate (green arrow); stasis of central vein (); NAS score mild to moderate, grade 1/2: steatosis—grade 1, ballooning degeneration—grade 2, lobular inflammation—grade 2 (2–4 foci/×20 field), portal inflammation—grade 2. (D1–D3). Dexa+ LP probiotics group; H&E stain; (D1 20×) and (D2 40×, D3 40×). Normal lobular architecture, with the restoration of hepatocyte shape and structure; focal lymphocytic inflammatory infiltrate in the portal triads was maintained (green arrow); focal hemosiderin pigment (black arrow) was spotted in the centrilobular zone and the connective tissue belonging to the portal triads; NAS score mild, grade 1: steatosis—grade 1, ballooning—grade 1, lobular inflammation—grade 0, portal inflammation—grade 1.