Naringin and Hesperidin Counteract Diclofenac-Induced Hepatotoxicity in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities.

Rasha A Hassan,Kamal A Amin,Walaa G Hozayen,Osama M Ahmed,Haidy T Abo Sree,Hessah M Al-Muzafar,Anderson J Teodoro

doi:10.1155/2021/9990091

Abstract

This study is aimed at evaluating the preventive effect and at suggesting the mode of actions of naringin and hesperidin and their combination in diclofenac-induced hepatotoxicity. Male Wistar rats, intraperitoneally injected with diclofenac sodium (3 mg/kg b.wt/day), were orally treated with naringin (20 mg/kg b.wt/day) and hesperidin (20 mg/kg b.wt/day) and their combination for 4 weeks. The administrations of naringin and hesperidin to diclofenac-injected rats led to a significant decrease in the elevated serum ALT, AST, LDH, ALP, GGT, total bilirubin, TNF-α, and IL-17 levels as well as liver lipid peroxidation and liver p53 and caspase-3 mRNA expressions. In contrast, serum IL-4 level, liver GSH content, and liver GPx and SOD activities increased. In association, diclofenac-induced deleterious histological alterations including hydropic degeneration, cytoplasmic vacuolization, apoptosis, and focal hepatic necrosis of hepatocytes associated with inflammatory cells' infiltration were remarkably improved by treatments with naringin and hesperidin. In conclusion, naringin, hesperidin, and their combination, which was the most potent, counteract diclofenac-induced liver injury via antioxidant, anti-inflammatory, and antiapoptotic actions. Thus, this study recommends the use of naringin and hesperidin or their combination to resolve the side effects of drugs like diclofenac on the liver.

Highlights

Nonsteroidal anti-inflammatory drugs )NSAIDs) have various side effects [1]
The cotreatment of diclofenac-injected animals with naringin and/or hesperidin induced a decrease in these elevated levels
The cotreatment of diclofenac-injected animals with hesperidin induced a significant effect (p < 0:05) on the elevated Alanine transaminase (ALT), aspartate transaminase (AST), Lactate dehydrogenase (LDH), GGT, and total bilirubin levels while it failed to produce a significant effect in serum Alkaline phosphatase (ALP) activity (p < 0:05)

Summary

Introduction

Nonsteroidal anti-inflammatory drugs )NSAIDs) have various side effects [1]. Diclofenac, as one of this category of drugs, is a phenylacetic acid derivative that has long been used as analgesic and an anti-inflammatory drug to treat certain conditions [2]. Diclofenac has potent therapeutic effects, its sustained use is associated with serious dose-dependent adverse effects [3]. Increase in the oxidative stress and suppression of antioxidant defense system were reported by various publications that they were implicated in the induction of toxicity and side effects of the drug [4, 5]. The use of antioxidant such as citrus flavonoid in combination with the diclofenac may counteract the diclofenac-induced oxidative stress and thereby may prevent drug side effects and toxicity

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Conclusion