Protective effects of melatonin and l-carnitine against methotrexate-induced toxicity in isolated rat hepatocytes

Isoniazid is one of the most commonly used drugs to treat tuberculosis. Its administration is associated with a high incidence of hepatotoxicity. The aim of this study was to establish the protective effects of taurine against cytotoxicity induced by isoniazid and its suspected toxic metabolite hydrazine in isolated rat hepatocytes by measuring reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial depolarisation, reduced glutathione (GSH), and oxidised glutathione (GSSG). Isoniazid caused no significant ROS formation in normal hepatocytes, but in glutathione-depleted cells it was considerable. Hydrazine caused ROS formation and lipid peroxidation in both intact and glutathione-depleted cells. Both isoniazid and hydrazine caused mitochondrial membrane depolarisation. Hydrazine lowered cellular GSH reserve and increased GSSG. Taurine (200 μmol L-1) and N-acetylcysteine (200 μmol L-1) effectively countered the toxic effects of isoniazid and/or hydrazine by decreasing ROS formation, lipid peroxidation, and mitochondrial damage. Taurine prevented depletion of GSH and lowered GSSG levels in hydrazine-treated cells. This study suggests that the protective effects of taurine against isoniazid and its intermediary metabolite hydrazine cytotoxicity in rat hepatocytes could be attributed to antioxidative action.

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Protective Effects of Phenolic Compounds on CCl4-Induced Toxicity in Isolated Rat Hepatocytes

Zeitschrift für Naturforschung C ◽

10.1515/znc-1992-3-417 ◽

1992 ◽

Vol 47 (3-4) ◽

pp. 275-279 ◽

Cited By ~ 12

Author(s):

M.T. Añón ◽

A. Ubeda ◽

M.J. Alcaraz

Keyword(s):

Phenolic Compounds ◽

Phenolic Acids ◽

Rat Hepatocytes ◽

Protective Effects ◽

Chlorogenic Acids ◽

Spontaneous Release ◽

Isolated Rat Hepatocytes ◽

Cinnamic Acid Derivatives ◽

Benzoic Acid Derivatives ◽

Isolated Rat

Abstract The protective effects of a series of phenolic compounds, phenolic acids and flavonoids on the cytotoxicity of CCl4 in rat hepatocytes were studied. A number of flavones, 7,8-dihydroxyflavone, luteolin and hypolaetin-8-glucoside, flavonols, morin, quercetin, robinetin and gossypin, phenolic acids, gallic, caffeic and chlorogenic acids, as well as the flavane ( + )-catechin significantly inhibited alanine amine transferase (ALT) release. Catechol groups are determinant for the protective activity of flavonoids and cinnamic acid derivatives, as well as the resorcinol or pyrogallol moieties in the B ring of flavonoids. In benzoic acid derivatives a pyrogallol group is required. This feature is associated with the inhibition of ALT spontaneous release.

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Protective effect of metallothionein on cadmium toxicity in isolated rat hepatocytes

Biochemical Journal ◽

10.1042/bj2300395 ◽

1985 ◽

Vol 230 (2) ◽

pp. 395-402 ◽

Cited By ~ 57

Author(s):

W S Din ◽

J M Frazier

Keyword(s):

Protective Effect ◽

Cadmium Toxicity ◽

Membrane Damage ◽

Rat Hepatocytes ◽

Protective Effects ◽

Isolated Rat Hepatocytes ◽

Detoxification Mechanism ◽

Isolated Rat

An isolated rat hepatocyte preparation was used to study the cellular toxicity of cadmium and the protective effects of metallothionein on cadmium-induced toxicity. Exposure of primary suspension cultures of isolated rat hepatocytes to Cd2+ (0-35.7 microM) for 15 min resulted in a dose-dependent reduction in the synthesis of cellular proteins during a subsequent 6 h incubation. Such inhibition could not be correlated with cellular lethality or gross membrane damage. Pre-induction of metallothionein in hepatocytes by zinc treatment in vivo of donor rats protected hepatocytes in vitro from cadmium-induced inhibition of protein synthesis. The protective effects in zinc-pre-induced hepatocytes are not due to alterations in the level of total cellular cadmium, but could be accounted for by the redistribution of intracellular cadmium in the presence of high levels of zinc-metallothionein. The data suggest that metallothionein exerts its protective effect by a kinetic detoxification mechanism, i.e. a decrease in reactive intracellular cadmium.

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Cytoprotective effects of silafibrate, a newly-synthesised siliconated derivative of clofibrate, against acetaminophen-induced toxicity in isolated rat hepatocytes

Archives of Industrial Hygiene and Toxicology ◽

10.2478/10004-1254-65-2014-2434 ◽

2014 ◽

Vol 65 (2) ◽

pp. 169-178 ◽

Cited By ~ 1

Author(s):

Sara Nafisi ◽

Reza Heidari ◽

Mohammad Ghaffarzadeh ◽

Mojtaba Ziaee ◽

Hossein Hamzeiy ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Inflammatory Responses ◽

Liver Perfusion ◽

Rat Hepatocytes ◽

Protective Effects ◽

Isolated Cells ◽

Isolated Rat Hepatocytes ◽

Ros Formation ◽

Isolated Rat

AbstractAcetaminophen (N-acetyl para amino phenol, APAP) is a widely used antipyretic and analgesic drug responsible for various drug-induced liver injuries. This study evaluated APAP-induced toxicity in isolated rat hepatocytes alongside the protective effects of silafibrate and N-acetyl cysteine (NAC). Hepatocytes were isolated from male Sprague-Dawley rats by collagenase enzyme perfusion via the portal vein. This technique is based on liver perfusion with collagenase after removing calcium ions (Ca2+) with a chelator. Cells were treated with different concentrations of APAP, silafibrate, and NAC. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation, and mitochondrial depolarisation were measured as toxicity markers. ROS formation and lipid peroxidation occurred after APAP administration to rat hepatocytes. APAP caused mitochondrial depolarisation in isolated cells. Administration of silafibrate (200 μmol L-1) and/or NAC (200 μmol L-1) reduced the ROS formation, lipid peroxidation, and mitochondrial depolarisation caused by APAP. Cytotoxicity induced by APAP in rat hepatocytes was mediated by oxidative stress. In addition, APAP seemed to target cellular mitochondria during hepatocyte damage. The protective properties of silafibrate and/or NAC against APAP‑induced hepatic injury may have involved the induction of antioxidant enzymes, protection against oxidative stress and inflammatory responses, and alteration in cellular glutathione content.

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