Protective Activity of Total Polyphenols from Genista quadriflora Munby and Teucrium polium geyrii Maire in Acetaminophen-Induced Hepatotoxicity in Rats.

Nacera Baali,Chantal Wrutniak-Cabello,Souad Ameddah,Samiya Baali,Laurence Pessemesse,Samir Benayache,Gérard Cabello,Christine Feillet-Coudray,Zahia Belloum,Gilles Fouret,Fadila Benayache,Beatrice Chabi

doi:10.3390/nu8040193

Nacera Baali, Chantal Wrutniak-Cabello + Show 10 more

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https://doi.org/10.3390/nu8040193

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Abstract

Oxidative stress is a major cause of drug-induced hepatic diseases and several studies have demonstrated that diet supplementation with plants rich in antioxidant compounds provides a variety of health benefits in these circumstances. Genista quadriflora Munby (Gq) and Teucrium polium geyrii Maire (Tp) are known to possess antioxidant and numerous biological properties and these endemic plants are often used for dietary or medicinal applications. Herein, we evaluated the beneficial effect of rich-polyphenol fractions of Gq and Tp to prevent Acetaminophen-induced liver injury and investigated the mechanisms involved in this protective action. Rats were orally administered polyphenolic extracts from Gq or Tp (300 mg/kg) or N-acetylcysteine (NAC: 200 mg/kg) once daily for ten days prior to the single oral administration of Acetaminophen (APAP: 1 g/kg). The results show that preventive administration of polyphenolic extracts from Gq or Tp exerts a hepatoprotective influence during APAP treatment by improving transaminases leakage and liver histology and stimulating antioxidant defenses. Besides, suppression of liver CYP2E1, GSTpi and TNF-α mRNA levels, with enhancement of mitochondrial bioenergetics may contribute to the observed hepatoprotection induced by Gq and Tp extracts. The effect of Tp extract is significantly higher (1.5–2 fold) than that of Gq extract and NAC regarding the enhancement of mitochondrial functionality. Overall, this study brings the first evidence that pretreatment with these natural extracts display in vivo protective activity against APAP hepatotoxicity through improving mitochondrial bioenergetics, oxidant status, phase I and II enzymes expression and inflammatory processes probably by virtue of their high total polyphenols content.

Highlights

Human beings are exposed on a daily basis to toxic chemicals and pathogens, which cause serious health problems
The total polyphenol content (TPC) found in n-BuOH extracts was significantly lower for Genista quadriflora Munby (Gq) (228 ̆ 5 mg GAE/g of extract) than for Teucrium polium geyrii Maire (Tp) (251 ̆ 4 mg GAE/g of extract, Student’s t: p < 0.01)
We have focused our attention on Genista quadriflora Munby (Gq) and Teucrium polium geyrii Maire (Tp)

Summary

Introduction

Human beings are exposed on a daily basis to toxic chemicals and pathogens, which cause serious health problems. Acetaminophen or paracetamol (N-acetyl-p-aminophenol; APAP) is one of the most extensively used analgesic and antipyretic agent worldwide It is considered as a safe drug at normal therapeutic doses; its overdoses are known to produce acute hepatic necrosis, which may be fatal [1]. Development of liver injury by APAP is attributed to the formation of a reactive metabolic, N-acetyl-p-benzoquinoneimine (NAPQI), through oxidative metabolism mediated mainly by cytochrome P450 [2]. This product is detoxified through reaction with reduced glutathione (GSH); following a hepatotoxic dose of APAP, liver GSH levels are depleted and NAPQI covalently binds primarily to proteins cystein groups as 3-(cysteine-S-y) acetaminophen adducts [2]. More recent studies have shown the development of oxidative and nitrosative stress within mitochondria [5,6,7], and mitochondrial membrane depolarization and onset of the mitochondrial permeability transition [5,8,9]

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