l-Proline Alleviates Kidney Injury Caused by AFB1 and AFM1 through Regulating Excessive Apoptosis of Kidney Cells

Toxins (Basel). 2019 Apr 16;11(4):226. doi: 10.3390/toxins11040226.

Abstract

The toxicity and related mechanisms of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in the mouse kidney were studied, and the role of l-proline in alleviating kidney damage was investigated. In a 28-day toxicity mouse model, thirty mice were divided into six groups: control (without treatment), l-proline group (10 g/kg body weight (b.w.)), AFB1 group (0.5 mg/kg b.w.), AFM1 (3.5 mg/kg b.w.), AFB1 + l-proline group and AFM1 + l-proline group. Kidney index and biochemical indicators were detected, and pathological staining was observed. Using a human embryonic kidney 293 (HEK 293) cell model, cell apoptosis rate and apoptotic proteins expressions were detected. The results showed that AFB1 and AFM1 activated pathways related with oxidative stress and caused kidney injury; l-proline significantly alleviated abnormal expressions of biochemical parameters and pathological kidney damage, as well as excessive cell apoptosis in the AF-treated models. Moreover, proline dehydrogenase (PRODH) was verified to regulate the levels of l-proline and downstream apoptotic factors (Bax, Bcl-2, and cleaved Caspase-3) compared with the control (p < 0.05). In conclusion, l-proline could protect mouse kidneys from AFB1 and AFM1 through alleviating oxidative damage and decreasing downstream apoptosis, which deserves further research and development.

Keywords: aflatoxin B1; aflatoxin M1; apoptosis; l-proline; proline dehydrogenase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Aflatoxin B1 / toxicity*
  • Aflatoxin M1 / toxicity*
  • Animals
  • Apoptosis / drug effects
  • HEK293 Cells
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mice
  • Oxidative Stress / drug effects*
  • Proline / pharmacology
  • Proline / therapeutic use*
  • Proline Oxidase / metabolism
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Toxicity Tests, Subacute

Substances

  • Protective Agents
  • Aflatoxin M1
  • Proline
  • Aflatoxin B1
  • Proline Oxidase