Evaluation of ameliorative ability of Silibinin against zidovudine and isoniazid-induced hepatotoxicity and hyperlipidaemia in rats: Role of Silibinin in Phase I and II drug metabolism

Ramanathan, Raghu; Karthikeyan, S.

doi:10.1016/j.cbi.2017.06.008

Cited by 13 publications

(15 citation statements)

References 39 publications

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“…A total of 34 studies were identified, 17 of which were excluded based on title and abstracts, and 10 full-texts were retrieved. However, one [3] was not an RCT, seven were duplicate publications of the same study, nine [15, 25–32] were animal studies, four [14, 16, 33, 34] were in vitro research studies, three [35–37] were irrelevant to this study, one [38] was a conference summary without available results, one [39] was a clinical trial with unknown recruitment status, one [40] study's data could not be used, and one [41] was a review. Therefore, finally five RCTs [19–21, 42, 43] were included in the meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

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

Tao

Zhang

et al. 2019

Canadian Journal of Gastroenterology and Hepatology

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Background Prophylactic therapy with silymarin to prevent the development of antituberculosis drug-induced liver injury (anti-TB DILI) has been under debate. We aimed to evaluate the effect of silymarin in the prevention of anti-TB DILI. Methods We searched MEDLINE, PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to 30th November 2018. Randomized controlled trials (RCTs) that compared silymarin and placebo to prevent anti-TB DILI were included. All statistical analyses were conducted using STATA 12.0 software. Standardized mean difference (SMD) and risk ratio (RR) with 95% confidence intervals (CIs) were used to evaluate the effect of silymarin. The quality of included studies was assessed according to Cochrane handbook. Funnel plots and Egger's tests were carried out to evaluate publication bias. Sensitivity analysis was conducted to assess the influence of each study. ResultsA total of 1198 patients from five RCTs (585 with silymarin and 613 with placebo groups) were included. Overall, silymarin significantly reduced the occurrence of anti-TB DILI at week 4 [RR: 0.33, 95% CI (0.15, 0.75)]. In addition, silymarin exerted protective effect on liver function in patients undergoing anti-TB drugs [SMD = − 0.15, 95% CI (−0.24, −0.07), P < 0.001 (ALT); SMD =−0.14, 95% CI (−0.23, −0.06), P = 0.001(AST); SMD =−0.12, 95% CI (−0.20, −0.03), P = 0.008 (ALP)]. Silymarin led to similar AEs in placebo groups [OR: 1.09, 95% CI (0.86, 1.39), P = 0.47]. Conclusion Prophylactic therapy of silymarin is contributed to a noticeably reduced risk of development of anti-TB DILI four weeks after the initiation. In addition, silymarin significantly improved the liver function in patients who are receiving anti-TB drugs.

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Section: Resultsmentioning

confidence: 99%

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

Tao

Zhang

et al. 2019

Canadian Journal of Gastroenterology and Hepatology

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“…Hence, we speculate that the levels of hepatotoxicity induced by AZT will certainly enhance, when it is coadministered with INH. 33 In the present study, we investigated the influence of AZT treatment on the pharmacokinetics of INH in order to understand whether these treatments have any influence on the disposition of INH and its hepatotoxic metabolites. It was observed that the C max , T max , plasma T 1/2 , AUC (0.5-4) , and Cl of INH, HYD, and ACHY were unaffected upon oral administration of AZT in INH-treated rats.…”

Section: Discussionmentioning

confidence: 99%

Investigations on the Influence of Zidovudine in the Pharmacokinetics of Isoniazid and Its Hepatotoxic Metabolites in Rats

Ramanathan

Karthikeyan

2017

Journal of Pharmacy Practice

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The HIV-infected patients are co-infected with many bacterial infections in which tuberculosis is most common found worldwide. These patients are often administered with combined therapy of anti-retroviral and anti-tubercular drugs which leads to several complications including hepatotoxicity or adverse drug interactions. The drug-drug interactions between the anti-retroviral and anti-tubercular drugs are not clearly defined and hence, this study was conducted to evaluate the pharmacokinetic drug-drug interactions of Zidovudine (AZT) with Isoniazid (INH) and its hepatotoxic metabolites. Seventy two rats were randomly divided into two major groups with their sub-groups each comprising 6 animals. The Group I received INH alone at a dose of 25 mg/kg; b.w and Group II received AZT (50 mg/kg; b.w) along with INH orally. Pharmacokinetic studies of INH and its metabolites i.e., acetyl hydrazine (ACHY) and hydrazine (HYD) shows that INH and ACHY attains maximum plasma concentration ( C) within 30 minutes and HYD attains C at 1 hour after INH administration and all these analytes disappear from plasma within 4 hours. Pharmacokinetic studies also revealed that AZT treatment did not showed any drug-drug interactions and have no effect on the T, plasma clearance, AUC, C and T of INH and its hepatotoxic metabolites.

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“…marin on DILI. Ramanathan and Sivanesan reported that 100 mg/kg silymarin significantly improved zidovudine and isoniazid-induced hepatotoxicity in rats (10). Silymarin reduced hepatotoxicity caused by resorcinol and rifampicin by inhibiting glutathione reductase and glutathione peroxidase activity in mice (11).…”

Section: Contextmentioning

confidence: 99%

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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Evaluation of ameliorative ability of Silibinin against zidovudine and isoniazid-induced hepatotoxicity and hyperlipidaemia in rats: Role of Silibinin in Phase I and II drug metabolism

Cited by 13 publications

References 39 publications

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

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

Investigations on the Influence of Zidovudine in the Pharmacokinetics of Isoniazid and Its Hepatotoxic Metabolites in Rats

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

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