Dose and Exposure Time-Dependent Renal and Hepatic Effects of Intraperitoneally Administered Fumonisin B₁ in Rats

Toxins (Basel). 2018 Nov 9;10(11):465. doi: 10.3390/toxins10110465.

Abstract

Male Wistar rats were treated intraperitoneally (i.p.) with fumonisin B₁ (FB₁; 0, 20, 50 and 100 mg/kg dietary dose equivalent) for 5 and 10 days (n = 24⁻24 in each setting) to gain dose- and time-dependent effects on antioxidant status and oxidative stress response, clinical chemical endpoints and liver, kidney and lung histopathology and lymphocyte damage (genotoxicity). FB₁ decreased feed intake, body weight gain and absolute liver weight, irrespective of the toxin dose. Relative kidney weight increased in the 10-day setting. Linear dose response was found for plasma aspartate aminotransferase, alanine aminotransferase, total cholesterol, urea and creatinine, and exposure time-dependence for plasma creatinine level. The latter was coupled with renal histopathological findings, tubular degeneration and necrosis and the detachment of tubular epithelial cells. The pronounced antioxidant response (reduced glutathione accretion, increasing glutathione peroxidase activity) referred to renal cortical response (5⁻10 days exposure at 50⁻100 ppm FB₁). Hepatic alterations were moderate, referring to initial phase lipid peroxidation (exposure time dependent difference of conjugated diene and triene concentrations), and slight functional disturbance (↑ total cholesterol). Lymphocyte DNA damage was moderate, supporting a mild genotoxic effect of FB₁.

Keywords: dose-dependence; fumonisin B1; genotoxicity; hepatotoxicity; nephrotoxicity; rat.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Fumonisins / administration & dosage
  • Fumonisins / toxicity*
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Injections, Intraperitoneal
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Lung / anatomy & histology
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • Time Factors

Substances

  • Fumonisins
  • fumonisin B1
  • Glutathione Peroxidase
  • Glutathione