Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats

Abstract

Background and objectives: Ascorbic acid, alpha lipoic acid (ALA) and silymarin are well-known antioxidants that have hepatoprotective effects. This study aims to investigate the effects of these three compounds combined with attenuating drug-induced oxidative stress and cellular damage, taking acetaminophen (APAP)-induced toxicity in rats as a model both in vivo and in vitro. Materials and Methods: Freshly cultured primary rat hepatocytes were treated with ascorbic acid, ALA, silymarin and their combination, both with and without the addition of APAP to evaluate their in vitro impact on cell proliferation and mitochondrial activity. In vivo study was performed on rats supplemented with the test compounds or their combination for one week followed by two toxic doses of APAP. Results: Selected liver function tests and oxidative stress markers including superoxide dismutase (SOD), malondialdehyde (MDA) and oxidized glutathione (GSSG) were detected. The in vivo results showed that all three pretreatment compounds and their combination prevented elevation of SOD and GSSG serum levels indicating a diminished burden of oxidative stress. Moreover, ascorbic acid, ALA and silymarin in combination reduced serum levels of liver enzymes; however, silymarin markedly maintained levels of all parameters to normal ranges. Silymarin either alone or combined with ascorbic acid and ALA protected cultured rat hepatocytes and increased cellular metabolic activity. The subjected agents were capable of significantly inhibiting the presence of oxidative stress induced by APAP toxicity and the best result for protection was seen with the use of silymarin. Conclusions: The measured liver function tests may suggest an augmented hepatoprotection of the combination preparation than when compared individually.

Impact of date palm pollen (Phoenix dactylifera) treatment on paracetamol-induced hepatorenal toxicity in rats

“…Recent studies of the beneficial effect of some natural compounds against the elevated serum biochemical markers due to APAP-induced hepatorenal toxicity in rats [50][51][52][53]. Our results showed DPP caused a significantly diminished the elevated serum hepatic and renal enzymes and lipid profiles.…”

Vitamin C Ameliorates the Cefepime-Induced Changes of Liver Enzymes, Histopathology and Proinflammatory Cytokines in Male Albino Rats

“…either by co-administration of vitamin C with cefepime or by administration of vitamin C after finishing the course of cefepime. Such improvement in the levels of liver enzymes together with the high degree of restoration of the normal histological appearance of the liver indicated the potent capability and the role of vitamin C to restore the normal functions of the hepatocytes, such effects were explained depending on the anti ROS effects of vitamin C. 62 Vitamin C is considered as a potent anti-inflammatory drug through the inhibition of ROS which is a mediator for production of proinflammatory cytokines in several inflammatory diseases. [63][64][65] Also, it has a protective effect against hepatotoxicity.…”

Modulation of NRF2/ARE pathway- and cell death-related genes during drug-induced liver injury

“…Buffers and solutions were prepared as previously published. 20 Under air laminar flow within the cell culture hood, liver cells were dispersed gently using sterile cell scrapers in a sterile petri dish within the buffered collection medium. Connective tissues and undigested tissue fragments were removed, and cell suspension was then strained in sterilized 100 mm pore nylon mesh cell strainer (SPL, India) into a conical centrifugation tube and prepared for culture as described by Shen et al 18 Within the cell suspension, cells were counted using dyeexclusion assay using 0.4% Trypan blue stain (Thermo Fisher, USA) under light microscope using a hemocytometer (Marienfeld-Superior, Germany).…”