The hepatoprotective effects of aquatic extract of Levisticum officinale against paraquat hepatocyte toxicity

• Published in: Pakistan journal of pharmaceutical sciences Vol. 30; no. 6(Supplementary); pp. 2363 - 2368
• Main Authors: Afarnegan, Hasan, Shahraki, Ali, Shahraki, Jafar
• Format: Journal Article
• Language: English
• Published: Pakistan 01.11.2017
• Subjects: Animals; Antioxidants - isolation & purification; Antioxidants - pharmacology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; Cytoprotection; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatocytes - pathology; Herbicides - toxicity; Levisticum - chemistry; Lipid Peroxidation - drug effects; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Membrane Potential, Mitochondrial - drug effects; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondria, Liver - pathology; Oxidative Stress - drug effects; Paraquat - toxicity; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Rats, Wistar
• ISSN: 1011-601X

Paraquat is extensively used as a strong nitrogen-based herbicide for controlling weeds in agriculture. This herbicide is extremely toxic to humans and induces multiorgan failure due to accumulation in the cells. So far, many instances of fatal poisoning have been reported. Paraquat is metabolized primarily in the liver. Accordingly, the effects of aquatic Levisticum officinale extract on biochemical factors and oxidative status were evaluated in hepatocytes exposed to paraquat in this study. The results showed that paraquat-induced hepatocyte destruction is mediated by reactive oxygen species (ROS) production. The aquatic extracts of Levisticum officinale (100, 200, and 300μg/mL) could prevent lipid peroxidation and reduction in the potential of mitochondrial membranes (P<0.05). The antioxidants, ROS scavengers (mannitol, dimethyl sulfoxide, and α-tocopherol), and mitochondrial permeability transition pore-sealing agent (carnitine) inhibited the effects of paraquat. The pore-sealing compound inhibited hepatotoxicity, indicating that paraquat induces cell death via mitochondrial pathways. Hepatic cell death due to paraquat could be prevented by hepatocyte pretreatment with aquatic Levisticum officinale extracts, antioxidants, and ROS scavengers; therefore, oxidative stress might directly reduce the mitochondrial membrane potential. In conclusion, paraquat hepatotoxicity may be associated with oxidative stress and maintained by the disruption of mitochondrial membrane potential. Levisticum officinale aquatic extract, presumably due to its strong antioxidant properties, could protect against the destructive effects of paraquat on rat hepatocytes.