Protective effects of thiopronin against isoniazid-induced hepatotoxicity in rats

Yue, Jiang; Dong, Guicheng; He, Chunyan; Chen, Jie; Liu, Yinghui; Peng, Rui

doi:10.1016/j.tox.2009.08.006

Cited by 31 publications

(18 citation statements)

References 35 publications

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“…Its pathogenic role in NASH has also been recognized in both animal experiments and human studies [27,37] . A recent study has also shown that tiopronin exerts its hepatoprotective activity against isoniazid-induced hepatotoxicity by reducing free radical generation in addition to its role as a scavenger via the inhibition of hepatic CYP2E1 [38] . In this study, the protein expression of CYP2E1 was also significantly decreased by tiopronin treatment in rats fed a high-fat diet.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats

et al. 2012

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Aim: To study the protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats. Methods: Male Sprague-Dawley rats were given a high-fat diet for 10 weeks. The rats were administered tiopronin (20 mg/kg) or a positive control drug ursodeoxycholic acid (UDCA, 15 mg/kg) via gavage daily from week 5 to week 10. After the rats were sacrificed, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), and liver homogenate FFA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured using commercial analysis kits. The expression levels of CYP2E1 mRNA and protein were determined using RT-PCR and immunoblot assays, respectively. Results: Tiopronin significantly lowered both the serum ALT and AST levels, while only the serum ALT level was lowered by UDCA. Tiopronin significantly decreased the serum and liver levels of TG, TC and FFA as well as the serum LDL-C level, and increased the serum HDL-C level, while UDCA decreased the serum and liver TC levels as well as the serum LDL-C level, but did not change the serum levels of TG, FFA and HDL-C. Tiopronin apparently ameliorated the hepatocyte degeneration and the infiltration of inflammatory cells in the livers, but UDCA did not affect the pathological features of the livers. Both tiopronin and UDCA ameliorated the mitochondrial abnormality in the livers. The benefits of tiopronin were associated with increased SOD and GSH-Px activities, and with decreased MDA activity and CYP2E1 expression in the livers. Conclusion: Tiopronin exerts protective effects against non-alcoholic steatohepatitis in rats, which may be associated with its antioxidant properties and regulation of lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats

et al. 2012

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“…It has been reported that tacrine-induced oxidative stress can be prevented by glutathione or vitamin E. 14,15 Additionally, some chemical entities containing mercapto group, such as Tiopronin (Figure 1), were clinically applied to treat the liver injury caused by chemical insults. 16 Therefore, tacrine derivates cooperated with additional antioxidant fragment might be favorable to conquer the toxicity of tacrine. Indeed, some tacrine−antioxidant hybrids have been reported such as lipocrine that protects cells against oxidative stress and NO-donor-tacrine hybrids that showed hepatoprotective properties.…”

Section: ■ Introductionmentioning

confidence: 99%

Multifunctional Mercapto-tacrine Derivatives for Treatment of Age-Related Neurodegenerative Diseases

Wang

Guan

et al. 2012

J. Med. Chem.

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Cooperating mercapto groups with tacrine in a single molecular, novel multifunctional compounds have been designed and synthesized. These mercapto-tacrine derivatives displayed a synergistic pharmacological profile of long-term potentiation enhancement, cholinesterase inhibition, neuroprotection, and less hepatotoxicity, emerging as promising molecules for the therapy of age-related neurodegenerative diseases.

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“…Moreover, in vitro experiments showed that one isoniazid metabolite – mono acethylhydrazine – increased the number of Salmonella typhimurium TA100 and TA1535 revertant mutations and the number of micronuclei in polychromatophylic erythrocytes, which could be evidence of its mutagenic action (Bhide et al 1984). The weak mutagenic effect of isoniazid and its ability to cause liver DNA injury was also demonstrated experimentally (Braun et al , 1984; Yue et al , 2009). Rifampicin genotoxicity investigation showed increased frequency of sister chromatids exchanges in bone marrow cells at doses of 160, 240 and 310 mg/kg b.w.…”

Section: Discussionmentioning

confidence: 87%

Damage of testicular cell macromolecules and reproductive capacity of male rats following co-administration of ethambutol, rifampicin, isoniazid and pyrazinamide

Shayakhmetova¹,

Bondarenko²,

Коваленко³

2012

Interdisciplinary Toxicology

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The necessity to minimize adverse effects of tuberculosis chemotherapy requires a comprehensive evaluation of the effects of antituberculosis drugs on the reproductive system and testicular cell macromolecules. The epidemiological situation of tuberculosis in Central and Eastern Europe is getting worse. Data on adverse effects of antituberculosis drugs are scare concerning particularly their effects on the reproductive system. The aim of the present study was to investigate the potential effect of ethambutol, rifampicin, isoniazid and pyrazinamide co-administration on lipid peroxidation, glutathione content and protein SH-groups, DNA fragmentation levels, the reproductive capacity of Wistar male rats and the antenatal development of their posterity. The rats (150–170 g) were divided into two groups: group I – received antituberculosis drugs suspended in 1% starch gel per os: ethambutol – 155 mg/kg b.w./day, rifampicin – 74.4 mg/kg b.w./day, isoniazid – 62 mg/kg b.w./day, pyrazinamide – 217 mg/kg b.w./day, group II (control) – received only starch gel in corresponding volumes. The contents of TBA-active compounds, glutathione and protein SH-groups in testis and sperm were determined spectrophotometrically, the DNA-fragmentation was determined using an UV transilluminator (BIORAD, USA), reproductive system indices were measured by standard methods. The co-administration of therapeutic doses of ethambutol, isoniazid, rifampicin and pyrazinamide to male rats during the period of spermatogenesis caused an increase in the rate of thiobarbituric acid reactive substances formation in testis and sperm, decrease of testis glutathione and protein SH-group contents, significant changes in DNA fragmentation, fatal decrease of male fertilizing capacity and fertility, and increase of pre- and post-implantation embryo lethality. The changes in reproductive indices could be the result of direct or indirect effects of one or more drugs investigated.

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Protective effects of thiopronin against isoniazid-induced hepatotoxicity in rats

Cited by 31 publications

References 35 publications

Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats

Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats

Multifunctional Mercapto-tacrine Derivatives for Treatment of Age-Related Neurodegenerative Diseases

Damage of testicular cell macromolecules and reproductive capacity of male rats following co-administration of ethambutol, rifampicin, isoniazid and pyrazinamide

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