Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital

Mrzljak, Anna; Košuta, Iva; Škrtić, Anita; Kanižaj, Tajana Filipec; Vrhovac, Radovan

doi:10.1159/000343651

Cited by 21 publications

(16 citation statements)

References 29 publications

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“…Goji berry, the fruit of Lycium barbarum L., has been recently involved in hepatitis too (Franco et al 2012;Arroyo-Martinez et al 2011). Finally, many reports of suspected liver injuries from noni (Morinda citrifolia L.) are reported (Waldman et al 2013;Yu et al 2011;Stadlbauer et al 2008;López-Cepero Andrada et al 2007;Yuce et al 2006;Stadlbauer et al 2005;Millonig et al 2005), even if hepatotoxicity of noni juice remains speculative (Mrzljak et al 2013;West and Deng 2011). In this scenario, which component of Euforia ® induced liver injury remains to be established.…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity of green tea: an update

2015

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Green tea (GT), obtained from the leaves of Camellia sinensis (L.) Kuntze (Fam. Theaceae), is largely used for its potential health benefits such as reduction in risk of cardiovascular diseases and weight loss. Nevertheless, it is suspected to induce liver damage. Present work reviews the hepatic adverse reactions associated with GT-based herbal supplements, published by the end of 2008 to March 2015. A systematic research was carried out on PubMed, MedlinePlus, Scopus and Google Scholar databases, without any language restriction. Moreover, some accessible databases on pharmacovigilance or phytovigilance were consulted. The causality assessment was performed using the CIOMS/RUCAM score. Nineteen cases of hepatotoxicity related to the consumption of herbal products containing GT were identified. The hepatic reactions involved mostly women (16/19); the kind of liver damage was generally classified as hepatocellular (16/19). The causality assessment between consumption of herbal preparation and hepatic reaction resulted as probable in eight cases and as possible in eleven cases. In seven cases, patients used preparations containing only GT, while twelve reactions involved patients who took multicomponent preparations (MC). The reactions induced by GT had a generally long latency (179.1 ± 58.95 days), and the outcome was always resolution, with recovery time of 64.6 ± 17.78 days. On the contrary, liver injury associated with MC had a shorter latency (44.7 ± 13.85 days) and was more serious in four cases that required liver transplantation and, when resolution occurred, the recovery time was longer (118.9 ± 38.79). MC preparations contained numerous other components, many of which are suspected to induce liver damage, so it is difficult to ascribe the toxicity to one specific component, e.g., GT. Present data confirm a certain safety concern with GT, even if the number of hepatic reactions reported is low considering the great extent of use of this supplement. The mechanism of GT hepatotoxicity remains unclear, but factors related to the patient are becoming predominant. A major safety concern exists when GT is associated with other ingredients that can interact between them and with GT, enhancing the risk of liver damage. Patients should be discouraged from using herbal or dietary supplements containing complex mixtures and should be encouraged to use herbal and dietary supplement possibly under supervision of healthcare professionals.

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Section: Discussionmentioning

confidence: 99%

Hepatotoxicity of green tea: an update

2015

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“…On the other hand, drug-induced hepatotoxicity is continuously emerging as a significant cause of liver disorders, representing today a leading cause of acute liver failure in economically developed countries (Mrzljak et al, 2013). During DOX therapy, the liver receives, accumulates and metabolizes high concentrations of DOX.…”

Section: Pretreatment Hepatoprotective Effect Of Regular Aerobic Traimentioning

confidence: 99%

Pretreatment Hepatoprotective Effect of Regular Aerobic Training Against Hepatic Toxicity Induced by Doxorubicin In Rats

Zolfagharzadeh

Roshan²

2013

Asian Pacific Journal of Cancer Prevention

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Background: Doxorubicin is an anthracycline antibiotic commonly used to treat a variety of cancers as a most effective antitumor. However, its clinical use is associated with the toxic effects in numerous healthy tissues. Here we investigated the pretreatment effect of regular aerobic exercise on oxidative stress in rats acutely exposed to DOX-induced hepatotoxicity. Materials and Methods: Forty-eight Wistar male rats were randomly divided into 2 groups: control and training. The training protocol included treadmill running between 25 to 54 min/day and 15 to 20m/min, 5 days/week for 6 weeks. At the end of the exercise training protocol, rats from the control and trained groups were again randomly separated into 3 subgroups: DOX10mg/kg, DOX20mg/kg and saline. All treatments were carried 24 h after the last exercise bout and animals were sacrificed 24 h after DOX and saline injections. Results: Administration of DOX (10 and 20 mg.kg -1 ) resulted in imbalance in biomarkers related to oxidants and antioxidants in liver tissue, as compared to control groups. Six weeks of pretreatment training led to a significant increase in nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as compared to the control+DOX 10 mg/kg group. Training before DOX 20 mg/kg administration also led to a significant increase in NO and SOD, and a significant decrease in malondialdehyde (MDA). In addition, there was a significant difference between DOX 10 mg/kg and DOX 20 mg/kg treatments in MDA levels, only. Conclusions: The results of the present study indicate that pretreatment with aerobic exercise induces positive adaptations and has a potential protective effect against doxorubicin (DOX)-induced hepatotoxicity with doses of 10 and 20 mg.kg.

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“…Phenolic acids are consistently associated with reduced risk of cardiovascular disease, cancer and other chronic diseases by mechanisms related to the scavenging of free radicals and as prooxidant metals (antioxidant), although there are reports for toxic effects of compounds isolated from the fruit of M. citrifolia (Ee et al, 2009;Nualsanit et al, 2012;Aziz et al, 2014). Earlier reports indicated that fruits (Millonig et al, 2005;Stadlbauer et al, 2005; Yüce (West et al, 2006;Lopez-Cepero et al, 2007) and juice (Sivagnanam et al, 2011;Mrzljak et al, 2013) of M. citrifolia are hepatotoxic in humans, since preparations for them are rich inanthraquinones and coumarins (scopoletin) (Ee et al, 2009), they induce generation of free radicals derived from oxygen and trigger oxidative stress. Free radicals cause depletion of intracellular reduced glutathione and mitochondrial membrane potential, thus initiating lipid peroxidation and eventually, cell death (Su et al, 2005;Bussmann et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Toxicogenetic profile of rats treated with aqueous extract from Morinda citrifolia fruits

Moraes¹,

Alencar²,

Islam³

et al. 2016

J. Med. Plants Res.

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Morinda citrifolia ((Family: Rubiaceae)) is extensively used in traditional medicine due to its antiinflammatory, antimicrobial, antitumoral, and anti-hypertensive activities. However, there is no substantial data about hepatotoxic and toxicogenetic effects. This study evaluated biochemical changes and hepatotoxic, genotoxic, and mutagenic effects of aqueous extract of the fruit of M. citrifolia (AEMC) in liver, bone marrow, and peripheral blood cells. Animals (Rattus novergicus, 5 males and 5 females) were divided into negative control, positive control (Cyclophosphamide 25 mg/kg), and AEMC (2.5, 5, and 10 mg/kg, by gavage). AEMC induced increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), especially at 10 mg/kg in female (174.8 ± 50.7, 221.4 ± 24.6, and 174.7 ± 14.3 U/L) and male (156.5 ± 21.6, 183.7 ± 21.5, and 147.3 ± 17.8 U/L) (p<0.05). Histological analysis of livers showed inflammatory cell infiltration, nuclear fragmentation, microvacuolization, cellular swelling, points of inflammatoy necrosis, and discrete microvesicular steatosis. DNA damage in hepatocytes was found in both genders, mainly at 10 mg/kg (Frequency of Damage: 78.1 ± 4.5 and 70.4 ± 7.3%; Index of Damage: 107.6 ± 14.2 and 136.0 ± 26.9 for male and female, respectively). Similar results were observed in bone marrow cells. The AEMC 5 and 10 mg/kg induced micronucleus formation (4.4 ± 0.8 and 7.8 ± 1.1; 7.4 ± 1.1 and 9.6 ± 1.4 for peripheral blood and bone marrow cells, respectively) (p<0.05). These findings suggest clastogenic and/or aneugenic effects and genetic instability activated by AEMC, indicating precaution regarding the consumption of formulations or folk preparations based on this plant.

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Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital

Cited by 21 publications

References 29 publications

Hepatotoxicity of green tea: an update

Hepatotoxicity of green tea: an update

Pretreatment Hepatoprotective Effect of Regular Aerobic Training Against Hepatic Toxicity Induced by Doxorubicin In Rats

Toxicogenetic profile of rats treated with aqueous extract from Morinda citrifolia fruits

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