Rotenone induces hepatotoxicity in rats by activating the mitochondrial pathway of apoptosis

Abstract

As a pesticide extracted from plants, rotenone is widely used to control plant pests. In order to explore the safety of rotenone in the environment, we took 60 healthy male SD rats and randomly divided them into rotenone low-dose group, rotenone medium-dose group, rotenone high-dose group, dimethyl sulfoxide group (DMSO), and control group. After 28 days of oral administration, the rat liver tissue ultrastructure, liver function, oxidative stress indexs, mitochondrial function, and apoptosis-related factors were tested to evaluate the hepatotoxicity and toxicological mechanism of rotenone. The results showed that rotenone significantly increased the hepatic index of rats and the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum. Rotenone can reduce the number of endoplasmic reticulum of hepatocyte, concentrate chromatin and make the hepatocyte nuclears irregular. Rotenone weakened the ATP synthesis ability in mitochondria, decreased the activity of ATP enzyme in mitochondria, and increased the mitochondrial membrane potential in the high-dose group. And it induced oxidative stress damage to the mitochondria of rat liver cells. Rotenone can upregulate the expression of pro-apoptotic factors and downregulate the expression of anti-apoptotic factors. These results indicate that oral rotenone in rats induced hepatotoxicity in a dose-dependent manner. The mechanism of rotenone poisoning is that oxidative stress damages organelles of hepatocyte such as mitochondria and endoplasmic reticulum, resulting in their function being weakened or lost, leading to hepatocyte apoptosis.

Keywords:

• Rotenone
• rats
• hepatotoxicity
• oxidative stress
• apoptosis

Acknowledgments

The authors express their gratitude to the members of the Veterinary Traditional Chinese Veterinary Laboratory and the Veterinary Physiology Laboratory at the College of Veterinary Medicine, Northeast Agricultural University for their help in collecting the samples.

Ethics approval and consent to participate

The experiments were conducted in strict accordance with Guiding Principles for the Experimental Animal Ethics Committee and were approved by the Animal Ethical Committee of Northeast Agricultural University (No: 20171120).

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by the National Natural Science Foundation Project of China, No. 32072909.