Combined protective effects of oligo-fucoidan, fucoxanthin, and L-carnitine on the kidneys of chronic kidney disease mice

Eur J Pharmacol. 2021 Feb 5:892:173708. doi: 10.1016/j.ejphar.2020.173708. Epub 2020 Nov 3.

Abstract

Chronic kidney disease (CKD) is a common global progressive disease, but there are no ideal drugs for the treatment. Fucoidan and fucoxanthin, and L-carnitine are one of the very few natural products that have a therapeutic effect on CKD in animal experiments. However, the combined effects of these compounds on CKD are unknown. We established a mouse CKD model by right nephrectomy with transient ischemic injury to the left kidney. Oligo-fucoidan and fucoidan were extracted from Laminaria japonica. We fed CKD mice with the two compounds and L-carnitine to evaluate the combined effects on CKD. Oligo-fucoidan and fucoidan inhibited renal fibrosis and reduced serum creatine in CKD mice to a greater extent than any single compound. L-carnitine had no measurable effect on renal fibrosis but promoted the protective effect of the mixture of oligo-fucoidan and fucoidan on renal function in CKD mice. In the two-month safety test, the combined mixture further improved renal function and did not elevate serum aspartate aminotransferase and alanine aminotransferase levels in CKD mice. Furthermore, the weights of CKD mice treated with the combination increased to the normal level. We also found that all oligo-fucoidan, fucoxanthin, and L-carnitine inhibit H2O2-induced apoptosis and activated Akt in rat renal tubular cells. Our results confirm that oligo-fucoidan, fucoxanthin, and L-carnitine have a combined protective effect on the kidneys. The combined mixture may be beneficial for CKD patients.

Keywords: Chronic kidney disease; Fucoxanthin; L-carnitine; Oligo-fucoidan; Renal fibrosis.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biomarkers / blood
  • Carnitine / pharmacology*
  • Cell Line
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Enzyme Activation
  • Fibrosis
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Mice
  • Mice, 129 Strain
  • Oxidative Stress / drug effects
  • Polysaccharides / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / pathology
  • Xanthophylls / pharmacology*

Substances

  • Biomarkers
  • Polysaccharides
  • Xanthophylls
  • fucoxanthin
  • fucoidan
  • Proto-Oncogene Proteins c-akt
  • Carnitine