Oleuropein and hydroxytyrosol rich extracts from olive leaves attenuate liver injury and lipid metabolism disturbance in bisphenol A-treated rats

Abstract

In the present study, we investigated the protective effects of oleuropein- and hydroxytyrosol-rich extracts obtained from olive leaves against bisphenol A (BPA)-induced hyperlipidemia and liver injury in male rats. For this purpose, four groups of male rats (8 per group) were used: control group (Control), rats treated with BPA, rats treated with both BPA and oleuropein (OLE-BPA), and rats treated with both BPA and hydroxytyrosol (HYT-BPA). After 60 days of treatment, the results obtained using the DXA technique showed that treatment with BPA (10 mg per kg b.w.) increased the body weight and adipose tissue mass in male rats. Moreover, plasma levels of triglycerides, total cholesterol, LDL-cholesterol, AST, ALT, LDH, and TNF-α increased. The immunohistochemical analysis revealed a significant increase in the expression of COX-2 and p53 and a decrease in the expression of Bcl-2 related to liver inflammation. Oral administration of oleuropein and hydroxytyrosol-rich extracts obtained from olive leaves at 16 mg kg-1 reduced both the body weight and adipose tissue mass. These extracts were able to ameliorate liver damage and improve the elevated levels of TG and liver enzymes of BPA-treated rats possibly through enhancing CAT and SOD activities. Western blot results revealed that administration of the abovementioned extracts decreased the protein expression of NF-κB and TNF-α through the p38 signaling pathway. Overall, the findings suggest that the olive leaf extracts possess hypolipidemic and hepatoprotective effects against BPA-induced metabolic disorders through enhancing the antioxidative defense system and regulating the important signaling pathway activities.

Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome

“…In bisphenol A‐treated rats, oleuropein significantly reduced malondialdehyde levels and increased COD and TEAC in both livers and kidneys of rats (A. Mahmoudi et al, ). Another study using bisphenol A also corroborated this in liver tissue and found increased SOD and CAT levels and improved trolox capacity to a level close to the control (A. Mahmoudi et al, ). Furthermore, an extract, rich in oleuropein‐related compounds, was found to protect against DNA damage from heterocyclic amines, which could occur due to development of oxidative stress (Fuccelli et al, ) and could help prevent carcinogenesis through this mechanism.…”

“…Further, antihyperlipidemic therapy in diabetics proves effective for reducing primary cardiovascular events (Jakob, Nordmann, Schandelmaier, Ferreira‐González, & Briel, ; Rafel et al, ), and increased levels of HDL have been associated with a reduced risk of adverse events (Goldbourt et al, ). Oleuropein has been shown to reduce serum LDL (Jemai et al, 2008; A. Mahmoudi et al, ; Khalili et al, ; Lepore et al, ; F. Hadrich, Garcia, et al, ), TC (Jemai et al, 2008; A. Mahmoudi et al, ; Khalili et al, ; I. Andreadou et al, ; F. Hadrich, Garcia, et al, ; 246, Y. Oi‐Kano et al, ), and serum triglycerides (Jemai et al, 2008; A. Mahmoudi et al, ; Khalili et al, ; I. Andreadou et al, ; F. Hadrich, Garcia, et al, ; Y. Oi‐Kano et al, ) while also increasing serum HDL (Jemai et al, 2008; A. Mahmoudi et al, ; Khalili et al, ; F. Hadrich, Garcia, et al, ). In wild‐type mice, oleuropein caused reduction in serum TG and TC but not in PPAR‐α null mice showing that effect was due to activation and upregulation of PPAR‐α mRNA with an increase in multiple PPAR‐α target genes (Malliou et al, ).…”

“…Oleuropein has been shown to activate AMPK (F. Hadrich, Garcia, et al, ), and considering AMPK's activation has been strongly linked to a reduction of inflammatory cytokines (Salt & Palmer, ). TNF‐α has also been shown to induce or potentiate ICAM‐1 (Fingar et al, ; Javaid et al, ), which oleuropein can inhibit (Lee et al, 2018; A. Mahmoudi et al, ). This may play a role in the prevention or attenuation of the inflammatory process involved in atherosclerotic plaque genesis.…”

“…Kim et al, ). A p38 signaling pathway blockage occurred in one study, reducing expression of TNF‐α and NF‐κB (A. Mahmoudi et al, ), and it reduced expression of NF‐kB (A. Mahmoudi et al, ; Scoditti et al, ) with one study indicating inhibition of its p65 subunit translocation (Scoditti et al, ). Furthermore, oleuropein has been shown to activate AMPK (F. Hadrich, Garcia, et al, ), and AMPK activation has been linked to a reduction in secretion of IL‐1β, IL‐6, and TNF‐α as it inhibits NF‐kB activation in many cell types.…”

“…In the study by Hur et al (2012), it was concluded that oleuropein does not regulate lipid‐droplet associated perilipin/ADRP/TIP47 family proteins including ADRP and AIP47. Furthermore, a study in which rats were fed with bisphenol A and oleuropein also reduced hepatic inflammation possibly through reducing the expression of p53 and COX‐2 and enhancing Bcl‐2 protein expression, improved oxidative stress through improving CAT and SOD activity (A. Mahmoudi et al, ).…”