Cytoprotective Effects of Taurine Against Toxicity Induced by Isoniazid and Hydrazine in Isolated Rat Hepatocytes

Abstract

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 signifi cant 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 ) 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.

Efficiency of hepatocyte pretreatment with coenzyme Q10 against statin toxicity

“…About 85-90 % of hepatocytes were viable at the time of isolation, as established by the trypan blue uptake test (17). Viable cells were suspended in Krebs-Henseleit buffer (1x10 6 cells mL -1 ) containing 12.5 mmol L -1 of HEPES and incubated under a stream of carbogen gas (95 % O 2 and 5 % CO 2 ) in continuously rotating roundbottomed 50 mL flasks at 37 °C.…”

“…The viability of cells treated with atorvastatin, simvastatin, lovastatin, and CoQ 10 was assessed using the trypan blue (0.1 %, w/v) uptake test described elsewhere (17) at incubation hour one, two, and three. For this test, atorvastatin, simvastatin and/or CoQ 10 were dissolved in methanol and lovastatin in dimethyl sulphoxide.…”

Protective Roles of N-acetyl Cysteine and/or Taurine against Sumatriptan-Induced Hepatotoxicity

“…[26][27][28][29] Beneficial effects of natural flavonol quercetin have been described in cardiovascular disorders, hepatotoxicity and cancer 30,31 as well as radiotoxicity. 32 This glycoside reduces hepatotoxicity included by sodium fluoride and acetaminophen.…”

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

“…After treating 1 mL aliquots of hepatocyte suspension (10 6 cells mL -1 ) with trichloroacetic acid (70 % w/v) and boiling the supernatant with thiobarbituric acid (0.8 % w/v) for 20 min, the absorbance of the observed colour was determined using an Ultrospec ® 2000 UV spectrophotometer at 532 nm (Pharmacia Biotech Cambridge, England) (29).…”

“…The cell pellet was then resuspended in 2 mL of fresh incubation medium containing 1.5 µmol L -1 rhodamine 123 and gently shaken in a thermostatic water bath at 37 °C for 10 min. Hepatocytes were separated by centrifugation (402 g for one min) and the amount of rhodamine 123 appearing in the incubation medium was measured fluorimeterically at 490 nm excitation and 520 nm emission wavelengths using a Jasco ® FP-750 spectrofluorometer (30).…”