Renoprotective Effects of Brown-Strain Flammulina velutipes Singer in Chronic Kidney Disease-Induced Mice Through Modulation of Oxidative Stress and Inflammation and Regulation of Renal Transporters

Int J Mol Sci. 2024 Nov 11;25(22):12096. doi: 10.3390/ijms252212096.

Abstract

Cisplatin, widely used in chemotherapy, acts through mechanisms such as oxidative stress to damage the DNA and cause the apoptosis of cancer cells. Although effective, cisplatin treatment is associated with considerable side effects including chronic kidney disease (CKD). Studies on brown-strain Flammulina velutipes Singer (FVB) have shown its significant antioxidant and immunomodulatory effects. High-performance liquid chromatography (HPLC) confirmed that the FVB extract contained gallic acid and quercetin. This study investigated whether FVB extract can improve and protect against cisplatin-induced CKD in mice. C57BL/6 mice were used as an animal model, and CKD was induced through intraperitoneal cisplatin injection. FVB was orally administered to the mice for 14 consecutive days. N-acetylcysteine (NAC) was administered in the positive control group. Organ pathology and serum biochemical analyses were conducted after the mice were sacrificed. Significant dose-dependent differences were discovered in body mass, kidney mass, histopathology, renal function, inflammatory factors, and antioxidant functions among the different groups. FVB extract reduced the severity of cisplatin-induced CKD in pathways related to inflammation, autophagy, apoptosis, fibrosis, oxidative stress, and organic ion transport proteins; FVB extract, thus, displays protective physiological activity in kidney cells. Additionally, orally administered high doses of the FVB extract resulted in significantly superior renal function, inflammatory factors, antioxidative activity, and fibrotic pathways. This study establishes a strategy for future clinical adjunctive therapy using edible-mushroom-derived FVB extract to protect kidney function.

Keywords: brown-strain Flammulina velutipes; chronic kidney disease; cisplatin; gallic acid; quercetin.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cisplatin* / adverse effects
  • Disease Models, Animal
  • Flammulina* / chemistry
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Kidney* / drug effects
  • Kidney* / metabolism
  • Kidney* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Oxidative Stress* / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Renal Insufficiency, Chronic* / chemically induced
  • Renal Insufficiency, Chronic* / drug therapy
  • Renal Insufficiency, Chronic* / metabolism
  • Renal Insufficiency, Chronic* / pathology

Substances

  • Cisplatin
  • Antioxidants
  • Plant Extracts

Grants and funding

The funding for this research came from Asia University (AUH-11151009 and ASIA-112-CMUH-15).