Curcumin prevents paracetamol-induced liver mitochondrial alterations

Abstract

Objective In the present study was evaluated if curcumin is able to attenuate paracetamol (PCM)-induced mitochondrial alterations in liver of mice. Methods Mice (n = 5-6/group) received curcumin (35, 50 or 100 mg/kg bw) 90 min before PCM injection (350 mg/kg bw). Plasma activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was measured; histological analyses were done; and measurement of mitochondrial oxygen consumption, mitochondrial membrane potential, ATP synthesis, aconitase activity and activity of respiratory complexes was carried out. Key findings Curcumin prevented in a dose-dependent manner PCM-induced liver damage. Curcumin (100 mg/kg) attenuated PCM-induced liver histological damage (damaged hepatocytes from 28.3 AE 7.7 to 8.3 AE 0.7%) and increment in plasma ALT (from 2300 AE 150 to 690 AE 28 U/l) and AST (from 1603 AE 43 to 379 AE 22 U/l) activity. Moreover, curcumin attenuated the decrease in oxygen consumption using either succinate or malate/glutamate as substrates (evaluated by state 3, respiratory control ratio, uncoupled respiration and adenosine diphosphate/oxygen ratio), in membrane potential, in ATP synthesis, in aconitase activity and in the activity of respiratory complexes I, III and IV. Conclusions These results indicate that the protective effect of curcumin in PCM-induced hepatotoxicity is associated with attenuation of mitochondrial dysfunction.

Effects of Curcuminoids Plus Piperine on Glycemic, Hepatic and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Placebo-Controlled Trial

“…We have previously found that curcuminoid supplementation improves the lipid profile and increases total antioxidant capacity in T2D patients [16,17], thereby supporting other available evidence on the role of curcuminoids in modifying cardiometabolic risk [18][19][20][21][22][23][24]. Previous experimental studies have also reported a protective effect of curcumin against hepatotoxicity [25][26][27]. In the present study, we evaluated the impact of curcuminoids plus piperine administration on glycemic, hepatic and inflammatory biomarkers in T2D patients.…”

Antioxidant dietary approach in treatment of fatty liver: New insights and updates

“…In particular, curcumin has been reported to increase oxygen consumption and respiratory chain complexes’ activities, to prevent oxidative stress and to restore ATP content. Such an improvement in mitochondrial function was also shown to be associated with prevention against the decrease in the activity of aconitase[70], an oxidative stress marker. In addition, curcumin facilitated β-oxidation in in vitro experiments (by up-regulation of CPT-1), reducing lipogenesis at the same time[64].…”

Curcumin Benefits as Antioxidant, Antiinflamation and Antiapoptosis Ameliorate Paracetamol Toxicity

“…As the antioxidant, curcumin binds directly to the toxic metabolite of paracetamol and decreases the use of GSH [10], and also neutralizes and scavengering the oxidant ROS and RNS. Indirectly, through the activation of nuclear factor (erythroid-derived-2)-like-2 (Nrf2) transcription factor by curcumin, the production of catalase, SOD, GST, and GPx in nucleus increase and release into cytosol (Granados-Castro et al, 2016) [1]. The increased level of GST stimulates GSH formation which increases the excretion of the paracetamol toxic metabolites [10].…”

“…Paracetamol or acetaminophen is also known as N-acetyl p-aminophenol has been used as an antipyretic and analgesic for more than 30 years. Paracetamol poisoning is the largest poisoning case according to the American Association of Poison Control Centers causes 140,000 cases of poisoning and approximately 100 mortalities in the year 2006 [1]. At therapeutic dose, paracetamol will be metabolized in the liver through a process of glucuronidation and sulfation and excreted from the cell, a small part will be metabolized by Cytochrome P450 especially CYP2E1 to N-acetyl-p-benzoquinoneimine (NAPQI) toxic product.…”