Citronellol protects renal function by exerting anti-inflammatory and antiapoptotic effects against acute kidney injury induced by folic acid in mice

Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):5927-5937. doi: 10.1007/s00210-024-03677-5. Epub 2024 Dec 2.

Abstract

Acute kidney injury (AKI) is characterized by an abrupt cessation of kidney function. Folic acid-induced renal tubular damage is marked by immense inflammation and apoptosis in the kidney. Citronellol is a type of natural monoterpene alcohol commonly used in traditional medicine. Citronellol possesses pharmacological properties such as antioxidants, anti-inflammatory, and analgesic effects. This study aimed to investigate the reno-protective effect of citronellol against folic acid-induced AKI in mice models. Mice were divided into four groups. In addition to control and AKI-induction groups, two treatment groups were mice that received 50 or 100 mg/kg/day of citronellol orally for four consecutive days. On day 4, mice also received a single injection of folic acid (250 mg/kg) and were euthanized after 48 h. Citronellol 50 and 100 mg/kg rescued renal function as indicated by the significant reduction of serum urea, serum creatinine, and gene expression of KIM-1 compared to the non-treated group. In addition, citronellol 50 and 100 mg/kg relieved renal inflammation by significantly downregulating NF-κB, IL-6, and IL-1β gene expressions compared to the non-treated mice. Furthermore, citronellol retarded renal apoptotic events by the significant decline in renal tissue BAX and cleaved caspase-3 levels compared to non-treated mice. Histopathological report of renal tissue provides further evidence that augments the above results. The study highlighted the importance of some natural compounds that could have a place in therapeutic procedures for kidney injury, as observed by the strong renal protective effects of citronellol against AKI and remarkable anti-inflammatory and antiapoptotic actions.

Keywords: Acute kidney injury; Apoptosis; Citronellol; Folic acid; Inflammation.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / drug therapy
  • Acute Kidney Injury* / metabolism
  • Acute Kidney Injury* / pathology
  • Acute Kidney Injury* / prevention & control
  • Acyclic Monoterpenes* / pharmacology
  • Animals
  • Anti-Inflammatory Agents* / pharmacology
  • Anti-Inflammatory Agents* / therapeutic use
  • Apoptosis* / drug effects
  • Disease Models, Animal
  • Folic Acid* / toxicity
  • Hepatitis A Virus Cellular Receptor 1 / genetics
  • Hepatitis A Virus Cellular Receptor 1 / metabolism
  • Kidney* / drug effects
  • Kidney* / metabolism
  • Kidney* / pathology
  • Male
  • Mice
  • Monoterpenes* / pharmacology

Substances

  • Acyclic Monoterpenes
  • citronellol
  • Anti-Inflammatory Agents
  • Folic Acid
  • Hepatitis A Virus Cellular Receptor 1
  • Havcr1 protein, mouse
  • Monoterpenes