Perturbations in phosphoinositide metabolism and protein kinase C activity in mouse liver following whole body irradiation.

The involvement of the signal transduction pathway in mouse liver following whole body irradition was investigated. Mice were exposed to 60Co gamma rays (3 Gy) and sacrificed after different time intervals. Various elements of phosphatidyl inositol signal transduction pathway were investigated. Alterations could be seen as early as 15 min of irradiation. These changes are reflected in elevation in DAG levels and increased activation of PKC, an enzyme which is involved in tumorigenesis. The chronological appearance of various transducers following whole body irradiation is of significance since these early effects may set the stage for radiation-induced tumorigenesis and hence may be used to manipulate tumor response to radiotherapy.

Effect of aflatoxin B in vitro on rat liver mitochondrial respiratory functions.

Isolated rat liver mitochondria were incubated with various concentrations of aflatoxin B (AFB) for different periods of time. Respiration rates were then measured with two substrates (succinate and glutamate). State 3 respiration rate (with added ADP) declined with increase in preincubation concentrations of AFB1 (0.15-0.50 mM). On the other hand, state 4 respiration rate (after depletion of added ADP) was found to increase with increased pretreatment concentration of AFB. As a consequence, respiratory control index was reduced attaining minimum value with 0.25 mM AFB and preincubation time of 10 min. The induced anomaly in mitochondrial respiratory functions appear to be due to membrane damage caused by interaction of reactive AFB1 metabolite generated by mitochondrial cytochrome P-450 enzymes with mitochondrial components.

Respiratory functions in kidney mitochondria following paracetamol administration to young-adult & old rats.

Effects of paracetamol treatment in vivo to young-adult (2-3 months) and old (22-24 months) rats at subtoxic (375 mg/kg) and toxic (750 mg/kg) doses on kidney mitochondrial energy metabolism were examined. Administration of paracetamol (both doses) to young-adult animals did not, in general, affect the respiratory functions of kidney mitochondria. On the other hand, treatment of toxic doses to aged animals resulted in decrease in the state 3 respiration rates with glutamate, pyruvate + malate and succinate as substrates. Succinoxidase activity was also impaired in this experimental group. With subtoxic doses, state 3 respiration rate was decreased only with pyruvate + malate as substrate. Results indicate that the in vivo administration of paracetamol impaired kidney mitochondrial energy metabolism in aged animals.

Effect of thyroidectomy and subsequent treatment with triiodothyronine on kidney mitochondrial oxidative phosphorylation in the rat.

The effect of thyroidectomy (Tx) and subsequent treatment with triiodothyronine (T3) on rat kidney mitochondrial oxidative phosphorylation was examined. Thyroidectomy resulted in lowering of state 3 respiration rates and cytochrome contents. Thyroidectomized animals administered with T3 (20 μg/100 g body wt) resulted in the nonsynchronous stimulation of state 3 respiration rates in kidney mitochondria with glutamate, β-hydroxybutyrate, succinate and ascorbate+TMPD as substrates. Cytochrome contents were also elevated differentially. Increase in the state 4 respiration rates was transient and reversible. However, primary dehydrogenases were not generally altered in the Tx and T3- treated Tx animals. The results thus indicate that the T3-treatment to Tx animals brings about differential and nonsynchronous increase in the respiratory parameters and respiratory chain components of kidney mitochondria.

Altered kinetic properties of liver mitochondrial membrane-bound enzyme activities following paracetamol hepatotoxicity in the rat.

The effects of treatment with subtoxic (375 mg/kg) and toxic (750 mg/kg) doses of paracetamol on NADH oxidase, succinoxidase and Mg2+-ATPase activities in rat liver submitochondrial particles were examined. In the NADH oxidase system, treatment with subtoxic doses of paracetamol resulted in a 37% increase in activation energy in the high temperature range (E1) while the phase transition temperature (Tt) for this system decreased by 9°C. Subtoxic doses caused a 43% decrease in E1. For the succinoxidase system, Tt decreased by 2·4 to 3·4°C after paracetamol administration. E2 increased by 42% only in the subtoxic-treatment group while E1 remained unaltered in both paracetamol-treated groups. For the Mg2+-ATPase system, subtoxic doses of paracetamol treatment did not change the values of E1, E2 and Tt whereas toxic dose treatment resulted in a 29% decrease in E2 with a concomitant increase in Tt by 2·4°C without any change in the value of E1 · The results thus suggest that treatment with toxic and subtoxic doses of paracetamol results in possible differential alterations in the membrane lipid milieu.