Autophagic Dysregulation and Challenges in Kidney-Damage-Resistant Balb/C Mice: A Pilot Study

Nowadays, acute kidney damage (AKI) is seen as a serious public health risk. Exposure to lipopolysaccharide (LPS), the primary outer membrane component of Gram-negative bacteria, causes a significant increase in AKI that is generated by sepsis. In this work, we attempted to show how LPS affects the kidneys by creating a mouse model of AKI generated by LPS. Three different dosages of LPS were injected: 125ug/kg (i.p.), 250ug/kg (i.p.), and 1 mg/kg (i.p.). The experiment was completed after 24 hours. Mice exposed to LPS had different BUN responses at the same dosages. Significant LPS-induced damage was seen in the kidney tissue, including renal tubules that had epithelial cell degeneration and necrosis, tubules that showed total obliteration or enlargement, blood vessel congestion, and a slight thickening of the glomerular basement membrane, overall, a perfect AKI model with unusual BUN levels in kidney injury resistant mice model. The expression of core autophagy genes in the kidneys showed distinct patterns during LPS-induced AKI: ATG5 and Beclin 1 levels decreased, indicating inhibition of autophagic initiation, but LC3B levels remained unchanged. On the other hand, there was a significant increase in ATG4 expression (p < 0.001). Dysregulation resulting in a deficient autophagic flux during AKI development is indicated by this imbalance, which showed a drop in initiation components and an increase in processing components (ATG4). Based on the blood chemistry, histopathological findings, and autophagy genes expression, this study prompts future researchers to modify the LPS dosage as well as animal strain (BALB/c) which is a resistant strain for kidney damage and its impact on autophagy.