Protective effect of canaboid type 2 receptor agonist(JWH-133) against hepatic endoplasmic reticulum stress induced by prangos ferulacea extract

Objective: The Prangos ferulacea (PF) plant, belonging to the Apiaceae family, is grown and widely consumed in many places around the world, including our country. Although hepatotoxic cases have been reported due to these uses, studies that fully reveal this toxic effect are not encountered. The purpose of this study was to examine whether P. ferulacea plant has hepatotoxic effect, and evaluate to the relationship of this effect with ER stress and proinflammatory cytokines, as well as the effect of JWH-133 on this toxicity. Material Method: Wistar albino male rats, 8-10 weeks old, were used in the study (n=37). The animals were divided into 4 groups according to the random assignment method: from the rats forming the group-1 control group, from the rats injected with the PF hydroalcoholic extract (PFE) group-2, from the rats injected with PFE and cannabinoid type2 receptor agonists (JWH-133) group-3. Group-4 included rats injected only with JWH-133. At the end of the study, rats were sacrificed. ALT and AST levels were measured from blood serum. From the homogenates obtained from half of the liver tissue, the values of CHOP, GRP78, ATF4, IL-17 and IL-23 were evaluated by ELISA method. In the other half of the liver tissue removed, the tissues were examined histologically with hematoxylin-eosin stain and immunohistochemically by Caspase-3 staining method. The results were calculated using appropriate statistical methods. Results: At the end of our study, the body weight of animals injected with PFE was found to be significantly lower. (P <0.05) There was no statistically significant difference between the groups in ER stress markers (CHOP, GRP78, ATF4) and IL-17 and 23. There was a significant difference in terms of ALT and AST levels compared to that of controls. (P <0.05) In immunohistochemical and histopathological evaluations, it was observed that caspase-3 was positive in PFE groups and there was a significant increase in tissue damage (p <0.05). On the other hand, in animals applied JWH-133 together with PFE, there was a significant improvement in tissue damage (p <0.005). Conclusion: In our study, it was found that Prangos ferulacea plant improved histopathologically liver damage significantly, but it did not have a significant effect on ER stress. In addition, JWH-133 has been shown to have a healing effect against damage.