Monocrotaline-induced oxidative imbalance and apoptosis in extrahepatic tissues: evidence from lung and kidney in mice
TL;DR
MCT induces marked oxidative stress in lung and kidney tissues and promotes apoptotic signaling, suggesting that PA toxicity involves systemic and extrahepatic organ damage through oxidative imbalance.
Abstract
Pyrrolizidine alkaloids (PAs) are plant toxins of increasing concern due to their toxic and carcinogenic properties. While the hepatotoxic effects of PAs are well established, limited information is available regarding oxidative stress–related damage in extrahepatic tissues. This study aimed to determine alterations associated with oxidative stress and apoptosis in plasma, lung, and kidney tissues following acute and subacute exposure to monocrotaline (MCT) in mice. Thirty male BALB/c mice were randomly assigned to three groups: control, acute exposure, and subacute exposure. The control group received saline, the acute exposure group received a single dose of 120 mg/kg MCT, and the subacute exposure group received the same dose three times at five-day intervals. Plasma, lung, and kidney samples were collected for biochemical and molecular analyses. Total antioxidant status (TAS) and total oxidant status (TOS) levels were measured using a spectrophotometric method in plasma and tissue samples. Furthermore, plasma total thiol (TT), native thiol (NT), and disulfide (DD) levels were determined. The expression levels of BAX and BCL-2 genes in lung and kidney tissues were assessed using qPCR. MCT exposure significantly increased plasma TOS and oxidative stress index (OSI) levels in both exposure groups compared with the control group (P < 0.05). In lung tissue, TOS and OSI levels were significantly elevated, whereas TAS showed a non-significant increase. In kidney tissue, only TOS levels were significantly increased. Plasma NT levels were significantly decreased (P < 0.001), while DD levels were significantly increased (P < 0.05). In addition, BAX expression increased and the BCL-2/BAX ratio decreased in lung and kidney tissues, indicating a shift toward a pro-apoptotic state. In conclusion, MCT induces marked oxidative stress in lung and kidney tissues and promotes apoptotic signaling, suggesting that PA toxicity involves systemic and extrahepatic organ damage through oxidative imbalance.