Ameliorative effect of ursolic acid on ochratoxin A-induced renal cytotoxicity mediated by Lonp1/Aco2/Hsp75

Abstract

Ochratoxin A (OTA) is a mycotoxin ubiquitous in feeds and foodstuffs. The water-insoluble pentacyclic triterpene bioactive compound, ursolic acid (UA), is widespread in various cuticular waxes of edible fruits, food materials, and medicinal plants. Although studies have reported that oxidative stress was involved in both the nephrotoxicity of OTA and the renoprotective function of UA, the role of stress-responsive Lon protease 1 (Lonp1) in the renoprotection of UA against OTA is still unknown. In this study, cell viability, reactive oxygen species (ROS) production, and several proteins’ expressions of human embryonic kidney 293T (HEK293T) cells in response to UA, OTA, and/or Lonp1 inhibitor CDDO-me treatment were detected to reveal the protective mechanism of UA against OTA-induced renal cytotoxicity. Results indicated that a 2 h-treatment of 1 μM UA could significantly alleviate the ROS production and cell death induced by a 24 h-treatment of 8 μM OTA in HEK293T cells (P < 0.05). Compared with the control, the protein expressions of Lonp1, Aco2 and Hsp75 were significantly inhibited after 8 μM OTA treating for 24 h (P < 0.05), which could be notably reversed by the pre-treatment and post-treatment of 1 μM UA (P < 0.05). The protein expressions of Lonp1, Aco2 and Hsp75 were inhibited by the addition of CDDO-me. The three protein expression trends were similar before and after the addition of CDDO-me. In conclusion, OTA could inhibit the expression of Lonp1, suppressing Aco2 and Hsp75 as a result, thereby activating ROS and inducing cell death in HEK293T cells, which could be alleviated by UA pre-treatment.