Prophylactic Therapy of Silymarin (Milk Thistle) on Antituberculosis Drug-Induced Liver Injury: A Meta-Analysis of Randomized Controlled Trials

Tao, Lina; Qu, Xiaoyu; Zhang, Yue; Song, Yanqing; Zhang, Sixi

doi:10.1155/2019/3192351

Cited by 34 publications

(28 citation statements)

References 43 publications

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“…Overall, silymarin significantly reduced the occurrence of anti-TB/antipsychotic DILI compared to the control group and no significant adverse reaction was found. Under the premise of consistent doses, the results were similar to those reported by Tao et al (19). The optimal treatment time for silymarin for preventing anti-TB/antipsychotic DILI was four weeks.…”

Section: Discussionsupporting

confidence: 86%

“…Therefore, it was important to evaluate whether silymarin has a liver-protecting (17) reported that silymarin had no significant effect on anti-TB DILI, but instead it caused liver damage, suggesting that silymarin may be ineffective in anti-TB DILI. However, Tao et al (19) reported that silymarin significantly reduced the incidence of anti-TB DILI and for four-week treatment was the best duration to protect the liver. It indicated that the treatment time is one of the effective factors in the treatment of anti-TB DILI with silymarin.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Tao et al (19) in a systematic review, reported that silymarin effectively reduced the occurrence of anti-TB DILI, and the best effect was obtained after four weeks of treatment. However, it is well known that the clinical efficacy of a drug is related not only to the duration of treatment, but also to the administration dose.…”

Section: Contextmentioning

confidence: 99%

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Silymarin in Preventing Anti-Tuberculosis and Antipsychotic Drug-Induced Liver Injury at Different Doses and Treatment Times: A Systematic Review

Sheng

Zhang

Yin

2019

Iran Red Crescent Med J

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Context: The therapeutic effect, the optimal treatment time, and the dose of silymarin for preventing anti-tuberculosis and antipsychotic drug-induced liver injury (anti-TB/antipsychotic DILI) remains controversial. We conducted the first systematic review and meta-analysis study to evaluate the clinical efficacy of silymarin in the treatment of anti-TB/antipsychotic DILI in several subgroups based on follow-up time and dose. Evidence Acquisition: We searched the keywords and free words of "silymarin (silibinin)" and "Anti-tuberculosis or antipsychotic drug-induced liver injury" in PubMed, Web of Science, Cochrane, Scopus, and clinicaltrials.gov for full text English articles and China Journal Full-text Database (CNKI) and China Medical Bio-Document Database (CBM) for full text Chinese articles. The searched papers were reserved for randomized controlled trials (RCTs). The Jadad quality scale was used to conduct quality assessments. Two observers (SY and HY) independently extracted the data. MD and OR values were calculated to evaluate the clinical efficacy of silymarin in anti-TB/antipsychotic DILI. The Q test and chi-square test were used for heterogeneity analysis. Results: Nine RCTs with 2,712 participants (1,351 in the silymarin group and 1,361 in the control group) satisfying the inclusion criteria were finally examined. Compared to the placebo group, silymarin at less than 300 mg/d dose significantly reduced the occurrence of anti-TB/antipsychotic DILI and serum liver enzymes AST and ALT whether for two weeks, four weeks, or eight weeks [pooled OR: 0.53, 95% CI: 0.35-0.78, P = 0.42, I 2 = 3%; pooled MD:-4.47, 95% CI:-7.00,-1.93, P = 0.70, I 2 = 0%, AST; pooled MD:-3.50, 95% CI:-6.08,-0.91, P = 0.58, I 2 = 0%, ALT]. However, no significant difference was found in serum liver enzyme TBIL compared to the control group [pooled MD:-0.02, 95% CI:-0.07,-0.04, P = 0.69, I 2 = 0%]. Silymarin at 315 mg/d significantly reduced the occurrence of anti-TB/antipsychotic DILI and serum liver enzymes AST, ALT, and TBIL for eight weeks [subtotal OR: 0.17, 95% CI: 0.08-0.39, I 2 = 76%] but no significant difference was found between the over 400 mg/d silymarin group and the control group [subtotal OR: 0.93, 95% CI: 0.20-4.39, I 2 = 76%]. No significant difference was found in the occurrence of adverse events compared to the control group [pooled OR: 0.94, 95% CI: 0.71-1.25, I 2 = 0%]. Compared to the control group, silymarin prolonged the occurrence of anti-TB/antipsychotic DILI [pooled SMD: 1.78, 95% CI: 1.65-1.91, I 2 = 42%]. Conclusions: Silymarin prolonged the occurrence of anti-TB/antipsychotic DILI and reduced the incidence of anti-TB/antipsychotic DILI without significant adverse effects. The optimal treatment time of silymarin to prevent anti-TB/antipsychotic DILI was related to its dose.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

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Silymarin in Preventing Anti-Tuberculosis and Antipsychotic Drug-Induced Liver Injury at Different Doses and Treatment Times: A Systematic Review

Sheng

Zhang

Yin

2019

Iran Red Crescent Med J

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“…The SOD enzyme whose purpose appears to reduce the harmful effects due to hydroxyl radical ( • OH − ) by scavenges O − 2 to H 2 O 2 consequently, reduction of SOD level indicates hepatic injury. Similarly, CAT enzyme degrades H 2 O 2 into water and oxygen to protect tissue from reactive oxygen species [40][41][42][43]. The risks of hepatotoxicity were raised because of an increase of free radicals and a lack of scavenging capacity of hepatocytes because of increased rates of antioxidant biomarkers [44].…”

Section: Discussionmentioning

confidence: 99%

Crocus sativus L. Extract Containing Polyphenols Modulates Oxidative Stress and Inflammatory Response against Anti-Tuberculosis Drugs-Induced Liver Injury

Wali

Pillai

Dhaheri

et al. 2020

Plants

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The purpose of this study is to analyze the polyphenolic rich extract of Crocus sativus L. petals (CSP) in modulating liver oxidative stress and inflammatory response status against rifampicin isoniazid (INH-RIF) drug-induced liver injury. The INH-RIF was administered for 14 days with varying doses in Wistar rats, while silymarin was administered as standard dose. We report the defensive impacts of CSP against INH-RIF induced liver oxidative stress and proinflammatory cytokine. The CSP treatment at both doses significantly controlled all modulating biochemical hepatic injury indicators and resulted in the attenuation of arbitral INH-RIF damage. The components present in CSP identified by LC–ESI-Q-TOF–MS were found to be flavonoids and fatty acids. It can be inferred that CSP possesses a hepatoprotective capacity against INH-RIF-mediated hepatic injury, which may prove to be a medically beneficial natural product for the management of drug-induced liver injury.

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“…It is well known that many drugs undergo hepatic metabolism and can induce, directly or through their active metabolites, hepatotoxicity. As has been observed with anti-tuberculosis drugs (ATDs), this may result in increased morbidity or mortality [87]. Hepatotoxicity may necessitate treatment discontinuation, drug interruption and substitution or dose adjustment [87].…”

Section: Drug-induced Liver Injurymentioning

confidence: 99%

Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review

Gillessen¹,

2020

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Silymarin, an extract from milk thistle seeds, has been used for centuries to treat hepatic conditions. Preclinical data indicate that silymarin can reduce oxidative stress and consequent cytotoxicity, thereby protecting intact liver cells or cells not yet irreversibly damaged. Eurosil 85 Ò is a proprietary formulation developed to maximize the oral bioavailability of silymarin. Most of the clinical research on silymarin has used this formulation. Silymarin acts as a free radical scavenger and modulates enzymes associated with the development of cellular damage, fibrosis and cirrhosis. These hepatoprotective effects were observed in clinical studies in patients with alcoholic or nonalcoholic fatty liver disease, including patients with cirrhosis. In a pooled analysis of trials in patients with cirrhosis, silymarin treatment was associated with a significant reduction in liverrelated deaths. Moreover, in patients with diabetes and alcoholic cirrhosis, silymarin was also able to improve glycemic parameters. Patients with drug-induced liver injuries were also successfully treated with silymarin. Silymarin is generally very well tolerated, with a low incidence of adverse events and no treatment-related serious adverse events or deaths reported in clinical trials. For maximum benefit, treatment with silymarin should be initiated as early as possible in patients with fatty liver disease and other distinct liver disease manifestations such as acute liver failure, when the regenerative potential of the liver is still high and when removal of oxidative stress, the cause of cytotoxicity, can achieve the best results.

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Prophylactic Therapy of Silymarin (Milk Thistle) on Antituberculosis Drug-Induced Liver Injury: A Meta-Analysis of Randomized Controlled Trials

Cited by 34 publications

References 43 publications

Silymarin in Preventing Anti-Tuberculosis and Antipsychotic Drug-Induced Liver Injury at Different Doses and Treatment Times: A Systematic Review

Silymarin in Preventing Anti-Tuberculosis and Antipsychotic Drug-Induced Liver Injury at Different Doses and Treatment Times: A Systematic Review

Crocus sativus L. Extract Containing Polyphenols Modulates Oxidative Stress and Inflammatory Response against Anti-Tuberculosis Drugs-Induced Liver Injury

Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review

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