Hepatoprotective potential of ethanolic extract of Ziziphus oenoplia (L.) Mill roots against antitubercular drugs induced hepatotoxicity in experimental models

Rao, Ch. V.; Rawat, Ajay Kumar Singh; Singh, A. P.; Singh, Arpita; Verma, Neeraj

doi:10.1016/s1995-7645(12)60040-6

Cited by 32 publications

(17 citation statements)

References 21 publications

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“…The best role of CYP2E1 is the production of reactive oxygen species which is a clear mechanism for the hepatotoxicity caused by isoniaizd (Yue et al, 2004). Rifampicin exaggerate the isoniazid hepatotoxicity possibly by increasing the production of hydrazine or inhibition of bile pathway (Dugasani et al, 2014;Rao et al, 2015). In this study, rifampicin and isoniazid significantly increased the serum levels of ALT, AST, ALP and billirubin while it decreased the level of TP.…”

Section: Discussionsupporting

confidence: 49%

Hepatoprotective effect of Monotheca buxifolia fruit against antitubercular drugs-induced hepatotoxicity in rats

Ullah¹,

Khan²,

Adhikari³

et al. 2016

Bangladesh J Pharmacol

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The present study investigates the hepatoprotective potential of Monotheca buxifolia fruit hydro-ethanolic extract, against isoniazid- and rifampicin- induced hepatotoxicity in rats. Phytochemical investigations lead to the isolation of oleanolic acid and isoquercetin. Pretreatment with M. buxifolia extract at doses of 150 and 300 mg/kg for 21 days, restored the isoniazid- and rifampicin-induced elevation of serum levels of alanine aminotransferase (p<0.001), aspartate aminotransferase (p<0.001 and p<0.05), alkaline phosphatase (p<0.001), billirubin (p<0.001) and total proteins (p<0.001) as well as afforded significant protection against histopathological changes in the liver. From these results, it is conceivable that M. buxifolia exhibited selective protective effect against isoniazid- and rifampicin-induced hepatotoxicity, mediated through the presence of oleanolic acid and isoquercetin.

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Section: Discussionsupporting

confidence: 49%

Hepatoprotective effect of Monotheca buxifolia fruit against antitubercular drugs-induced hepatotoxicity in rats

Ullah¹,

Khan²,

Adhikari³

et al. 2016

Bangladesh J Pharmacol

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“…Oxidative stress created from the imbalance between free radicals’ generation and removal following INH treatment has being proposed to be one of the causative mechanisms by which INH could produce hepatic damage (Shen et al, 2007; Rao et al, 2012). As indicated in Figure 4 , INH/LPS combination showed a significant reduction in both SOD and T-AOC levels with maximum reduction observed at animal group receiving INH 400 mg/kg, which were significantly improved after addition of DEX.…”

Section: Resultsmentioning

confidence: 99%

Dexamethasone Pretreatment Alleviates Isoniazid/Lipopolysaccharide Hepatotoxicity: Inhibition of Inflammatory and Oxidative Stress

et al. 2017

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Isoniazid (INH) remains a cornerstone key constitute of the current tuberculosis management strategy, but its hepatotoxic potentiality remains a significant clinical problem. Our previous findings succeed to establish a rat model of INH hepatotoxicity employing the inflammatory stress theory in which non-injurious doses of inflammatory-mediating agent bacterial lipopolysaccharides (LPS) augmented the toxicity of INH that assist to uncover the mechanisms behind INH hepatotoxicity. Following LPS exposure, several inflammatory cells are activated and it is likely that the consequences of this activation rather than direct hepatocellular effects of LPS underlie the ability of LPS to augment toxic responses. In this study, we investigated the potential protective role of the anti-inflammatory agent dexamethasone (DEX), a potent synthetic glucocorticoid, in INH/LPS hepatotoxic rat model. DEX pre-treatment successfully eliminates the components of the inflammatory stress as shown through analysis of blood biochemistry and liver histopathology. DEX potentiated hepatic anti-oxidant mechanisms while serum and hepatic lipid profiles were reduced. However, DEX administration was not able to revoke the principal effects of cytochrome P450 2E1 (CYP2E1) in INH/LPS-induced liver damage. In conclusion, this study illustrated the DEX-preventive capabilities on INH/LPS-induced hepatotoxicity model through DEX-induced potent anti-inflammatory activity whereas the partial toxicity seen in the model could be attributed to the expression of hepatic CYP2E1. These findings potentiate the clinical applications of DEX co-administration with INH therapy in order to reduce the potential incidences of hepatotoxicity.

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“…Lipopolysaccharide (LPS) is an outer cell wall membrane constituent of Gram-negative bacteria that has been comprehensively studied as an inflammatory agent with a major role in bacterial infections (11,12). Previous studies have suggested that LPS might intensify DILI (13-15), and, hence, a possible cornerstone role for LPS in INH-induced hepatotoxicity might be assumed.Oxidative stress, generated from the accumulation of reactive oxygen species (ROS), may be potentiated by different factors, including drugs and inflammation (16,17). In addition, oxidative stress plays a major role in several types of hepatic injury (18).…”

mentioning

confidence: 99%

“…Oxidative stress, generated from the accumulation of reactive oxygen species (ROS), may be potentiated by different factors, including drugs and inflammation (16,17). In addition, oxidative stress plays a major role in several types of hepatic injury (18).…”

mentioning

confidence: 99%

Role of Inflammatory and Oxidative Stress, Cytochrome P450 2E1, and Bile Acid Disturbance in Rat Liver Injury Induced by Isoniazid and Lipopolysaccharide Cotreatment

Hassan

Guo

Yousef

et al. 2016

Antimicrob Agents Chemother

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Isoniazid (INH), since its introduction in the year 1952, still serves as a frontline drug in tuberculosis treatment (1). Despite the fact that INH has been widely used as a first-line antitubercular agent (2, 3), its therapeutic value is usually accompanied by severe hepatotoxicity and lethal hepatic injury (4, 5). Although the pathophysiology of INH-induced liver injury might vary, the toxicity features of the drug, including hepatocellular steatosis, necrosis, and inflammatory infiltration, are nearly consistent (6, 7).Even though extensive studies expounding INH toxicity have been carried out, the exact mechanism of INH hepatotoxicity remains controversial. Among numerous established theories, an inflammatory stress theory has recently been widely used to explain the idiosyncrasy. One hypothesis is that inflammatory stress increases sensitivity to drug-induced liver injury (DILI) (8, 9). In this theory, an incidence of systemic inflammation might reduce the xenobiotic toxicity threshold, which could be easily accomplished by coadministration with an inflammatory agent (10), thus promoting drug toxicity. Lipopolysaccharide (LPS) is an outer cell wall membrane constituent of Gram-negative bacteria that has been comprehensively studied as an inflammatory agent with a major role in bacterial infections (11,12). Previous studies have suggested that LPS might intensify DILI (13-15), and, hence, a possible cornerstone role for LPS in INH-induced hepatotoxicity might be assumed.Oxidative stress, generated from the accumulation of reactive oxygen species (ROS), may be potentiated by different factors, including drugs and inflammation (16,17). In addition, oxidative stress plays a major role in several types of hepatic injury (18). Furthermore, with cytochrome P450 2E1 (CYP2E1) playing a major role in drug metabolism and the pathophysiology of DILI (19) and being considered a principal element in human susceptibility to chemical toxins (20), it plays a central part in oxidative stress, production of ROS, and hepatotoxic injury. Moreover, a previous report proposed that hepatic CYP2E1 plays a fundamental role in the propagation of INH-induced hepatotoxicity, mainly throughout ROS generation (21). Nevertheless, a full understanding of CYP2E1 as a major hepatotoxin-forming, catalyzing enzyme and its influence on INH-induced liver damage has not been completely achieved.Studies of the hepatotoxic mechanisms of INH were previously conducted using different animal models; however, results were accompanied by the absence of certain features of INH toxicity, i.e., delayed onset or inconsistency in severity compared to that in hu-

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Hepatoprotective potential of ethanolic extract of Ziziphus oenoplia (L.) Mill roots against antitubercular drugs induced hepatotoxicity in experimental models

Abstract: The results of this study strongly indicate that ethanolic extract of Z. oenoplia has a potent hepatoprotective action against INH + RIF induced hepatic damage in rats.

Cited by 32 publications

References 21 publications

Hepatoprotective effect of <i>Monotheca buxifolia</i> fruit against antitubercular drugs-induced hepatotoxicity in rats

Hepatoprotective effect of <i>Monotheca buxifolia</i> fruit against antitubercular drugs-induced hepatotoxicity in rats

Dexamethasone Pretreatment Alleviates Isoniazid/Lipopolysaccharide Hepatotoxicity: Inhibition of Inflammatory and Oxidative Stress

Role of Inflammatory and Oxidative Stress, Cytochrome P450 2E1, and Bile Acid Disturbance in Rat Liver Injury Induced by Isoniazid and Lipopolysaccharide Cotreatment

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