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Abstract: Effects of treatment with a single intra-peritoneal (i.p.) injection (0.84mgCd/kg body weight) of cadmium (Cd) on lipid/phospholipids profiles of rat brain microsomes and mitochondria were examined. At the end of one-week following treatment with Cd the microsomal total phospholipids (TPL) content was unchanged but the cholesterol (CHL) content increased. In one-month Cd-treated group both TPL and CHL contents increased. In one-week Cd-treated group the content of phosphatidylinositol (PI) decreased whereas that of lysophospholipid and phosphatidic acid (PA) increased. In one-month Cd-treated group the sphinghomyelin (SPM) and phosphatidycholine (PC) components increased whereas phosphatidyethanolamine (PE) and PA decreased. In mitochondria, CHL content increased in both Cd-treated groups. The content of TPL decreased only in one-month Cd-treated group. In one-week Cd-treated group the lysophospholipids increased whereas PI and phosphatidylserine (PS) decreased. In one-month group the lysophospholipids, PI and diphosphatidylglycerol (DPG) components decreased whereas PS and PE component increased. The results suggest that exposure to a single dose of Cd has differential and long-lasting effects on lipid/phospholipids profiles of rat brain microsomes and mitochondria. [Copyright &y& Elsevier]

Abstract: Objectives: : Effects of treatment with dehydroepiandrosterone (DHEA) on oxidative energy metabolism in rat liver and brain mitochondria were examined. Design and methods: : Young adult rats were administered DHEA (0.1, 0.2, 1.0 or 2.0 mg/kg body weight) by subcutaneous route for 7 consecutive days. Results: : DHEA treatment resulted in general, in stimulation of state 3 respiration rates without having any uncoupling effect on ADP/O ratios. The stimulation of state 3 respiration rate for a given substrate was dose dependent in a tissue-specific manner. Parallel increases in the contents of cytochromes aa3 and b were also noted. DHEA treatment stimulated the glutamate dehydrogenase (GDH) and succinate DCIP reductase (SDR) activities. Under the treatment conditions, mitochondrial ATPase activity was also stimulated. Conclusions: : Treatment with DHEA significantly stimulated oxidative energy metabolism in liver and brain mitochondria. [Copyright &y& Elsevier]

Abstract: The content of the neurosteroids, dehydroepiandrosterone (DHEA) in the brain decreases with aging. Also the oxidative energy metabolism is known to decrease with aging. Hence we examined the effects of treatment with DHEA (0.2 or 1.0mg/kg body weight for 7 days) on oxidative energy metabolism in brain mitochondria from old and young adult rats. State 3 respiration rates in brain mitochondria from old animals were considerably lower than those in young adults. Treatment with DHEA stimulated state 3 and state 4 respiration rates in both the groups of the animals in a dose-dependent manner. In the old rats following DHEA treatment, the state 3 respiration rates became comparable to or increased beyond those of untreated young adults. In contrast to the old rats, stimulatory effect of DHEA treatment was of greater magnitude in the young adults. However, at higher dose (1.0mg) the effect declined. Cytochrome aa 3 content in the brain mitochondria from old rats was significantly low but the content of cytochrome b was unchanged while the content of cytochromes c + c 1 had increased. Treatment with DHEA increased the content of cytochrome aa 3 and b in old as well as in young adult animals. Higher dose of DHEA (1.0mg) had adverse effect on the content of cytochrome c + c 1 . DHEA treatment stimulated ATPase activity in a dose-dependent manner in young adult rats whereas in the old rats the effect on ATPase activity was marginal. Dehydrogenases activities were somewhat lower in the old rats. DHEA treatment stimulated mitochondrial dehydrogenases activities in both the groups. Results of our studies suggest that judicious use of DHEA treatment can improve oxidative energy metabolism parameters in brain mitochondria from young adult as well as old rats. [Copyright &y& Elsevier]

Abstract: Early and late effects of alloxan-diabetes of lipid/phospholipid composition of rat brain microsomes and mitochondria were examined. In microsomes, early as well as late diabetic stages resulted in decrease in contents of total phospholipids (TPL) and increase in cholesterol (CHL). Insulin treatment restored TPL with further increase in CHL in 1 week group. In early diabetic stage there was increase in the sphingomyelin (SPM) while phosphatidylinositol (PI) and phosphatidylserine (PS) components decreased. Insulin treatment restored SPM and decreased the lysophospholipids (Lyso), PI, PS and phosphatidic acid (PA); phosphatidylethanolamine (PE) increased. In 1 month diabetic group phosphatidylcholine (PC) decreased while PI, PS and PE increased. Insulin treatment lowered the Lyso, SPM, PI, PS and PA while PC and PE increased. In mitochondria, at early stage of diabetes both CHL and TPL contents decreased; insulin treatment restored the former component. Late diabetic stage had no effect on CHL and TPL contents; insulin treatment brought about reduction in both. Diabetic state had marginal effect on phospholipid composition at both the stages. Insulin treatment had a generalized effect of lowering of PI and PS components and increasing diphosphatidylglycerol (DPG). The fluidity of microsomal membranes decreased progressively in the diabetic condition; insulin treatment fluidized the membrane at early stage. The fluidity of mitochondrial membranes increased in early diabetic stage and the effect was accentuated by insulin treatment. However, at the late stage the effects on membrane fluidity were marginal. [Copyright &y& Elsevier]

Abstract: Effects of STZ diabetes and treatment with insulin on cerebral mitochondrial metabolism in the male and female rats were examined. Diabetic state resulted in generalized decrease in the state 3 respiration rates in the males with practically all the substrates except glutamate where the opposite effect was seen. Diabetic state had no adverse effect on the respiratory activity in the females. Insulin treatment had no restorative effect in the males. By contrast in the females, adverse effects were noted. The cytochromes contents decreased in STZ diabetes with the effect being more pronounced in the males; treatment with 1 unit of insulin restored the cytochromes contents. STZ diabetes also resulted in decreased dehydrogenases activities with the effect being more pronounced in the females: insulin treatment resulted in hyper-stimulation of glutamate dehydrogenase and succinate DCIP reductase activities; restoration of malate dehydrogenase activity was only partial. The results point out that STZ diabetes and insulin treatments differentially affect cerebral mitochondrial energy metabolism in the male and female rats. [Copyright &y& Elsevier]

Abstract: Effect of neonatal hypothyroidism on kinetic properties of Ca2+-ATPase from rat brain synaptic plasma membranes and microsomes were examined. Neonatal hypothyroidism resulted in significant decrease in the enzyme activity in both the membrane systems. The synaptic membranes in control group displayed presence of one kinetic component whereas a low affinity component became evident in the hypothyroid group. In the microsomes, both control as well as hypothyroid groups showed presence of two kinetic components with the latter group showing two-fold increase in the K m. The Ca2+ binding characteristics were generally unaltered in the enzyme from both the membrane systems. Our results suggest that impairment in the Ca2+-ATPase activity together with altered kinetic properties could be one of the underlying biochemical mechanisms leading to CNS dysfunction as a consequence of thyroid hormone deprivation during critical stages of brain development. [Copyright &y& Elsevier]

Abstract: Cerebral microsomal membrane properties were assessed in the chronic condition of generalized seizure induced by picrotoxin (PTX) in rats. PTX-induced seizures resulted in increased lysophosphatidyl glycerol, phosphatidylcholine and phosphatidic acid components, while phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were significantly reduced by 19–73%. The cholesterol (CHL) content increased considerably by 25% without alteration in total phospholipids content. Microsomal membrane was more fluidized in the epileptic condition. Possible consequences of microsomal membrane alterations are discussed in terms of deregulation of Ca2+ homeostasis. In conclusion, alterations in the microsomal membrane properties may have a significant influence on the cerebral function in the chronic epileptic condition. [Copyright &y& Elsevier]

Abstract: Studies on Cd hepatotoxicity have focused mainly on induction of cytochrome P450 system and related enzymes. In the present study young adult male rats given a single intra-peritoneal injection of Cd (0.84mg Cd/kg body weight) and effects on kinetic parameters rat liver microsomal Na+, K+-ATPase and G6Pase were evaluated at the end of 1 month and 1 week. The substrate and temperature kinetics parameters were examined and attempts were made to seek correlation with changes in lipid/phospholipid profiles. The Na+, K+ ATPase activity decreased only in 1 week Cd-treated group but recovered at the end of 1 month. The activity resolved in two distinct kinetic components in control as well as the experimental groups. In 1 week Cd-treated group the K m value of both the components was unchanged, whereas V max value decreased. In 1-month Cd-treated group V max value only of component I increased. The catalytic efficiency of both the components was not affected in the experimental groups. In 1-week Cd-treated group the energy of activations at high-temperature range (E H) and low-temperature range (E L) decreased, whereas for 1-month Cd-treated group the energies of activations did not change. The G6Pase activity measured at 37°C was high only in 1-month Cd-treated group. The activity resolved in two kinetically distinguishable components in control as well as in the experimental groups. K m value of component I decreased in both the Cd-treated groups. In 1-month Cd-treated group the V max value of component II increased. The catalytic efficiency of G6Pase was unchanged despite changes in K m and V max. In 1-week Cd-treated group the E H and E L decreased, whereas only E L showed decrease in 1-month Cd-treated group. Cholesterol (CHL) content increased in both the Cd-treated groups. Content of lysophospholipid (Lyso), spinghomyelin (SPM) and phosphatidic acid (PA) increased, whereas phosphatidylcholine (PC) and phosphatidylserine (PS) decreased in 1-week Cd-treated group. In 1-month Cd group the Lyso, SPM, and PC increased while PC, phosphatidylethanolamine (PE) and PA decreased. In conclusion, Cd has short-term effects on microsomal Na+, K+-ATPase which are reversed by the end of 1 month and that G6Pase does not seem to be a target of Cd insult. [Copyright &y& Elsevier]

Abstract: Neonatal hypothyroidism was induced in rat pups by injecting 131I within two days of birth and the effects on kinetic properties of Na+, K+-ATPase from synaptic plasma membranes were examined. Neonatal hypothyroidism resulted in a generalized decrease in V max with ATP, Na+, K+ and Mg2+ together with an increase in the K m for ATP, appearance of a low affinity component for Na+ and allosteric characteristic for the Mg2+-dependent activity at high Mg2+ concentrations. Binding pattern for Na+ and Mg2+ changed. Our results suggest that impairment of Na+, K+-ATPase activity together with altered kinetic properties could be one of the underlying biochemical mechanism leading to central nervous system (CNS) dysfunctions as a consequence of thyroid hormone deprivation during critical stages of brain development. [Copyright &y& Elsevier]

Aluminum (Al) is considered a potential etiological factor in Alzheimer’s disease (AD). Neurotoxicity from excess brain exposure to Al is documented from both clinical observations and animal experiments. A key role of the acetylcholine system in memory disturbances that characterize AD has been reported. On this basis, we studied the effect of long-term Al feeding on kinetic properties of cholinesterases employing the rat as experimental model. Animals were given prolonged treatment with soluble salts of Al (100 mg AlCl3/kg body weight mixed with food for 100–115 days), and the kinetic properties of cholinesterases (acetylcholinesterase, AChE, and butyrylcholinesterase, BChE) were determined in different tissues. Prolonged treatment with Al had no effect on the Km values of the soluble and membrane-bound forms of AChE in the brain, but Vmax was instead decreased in all the components of soluble and membrane-bound forms of AChE in the brain. In addition, the Al treatment resulted in complete loss of the component II of erythrocyte membrane AChE. Surprisingly, after prolonged treatment with Al, higher Vmax was observed in all the components of soluble and membrane-bound forms of BChE in the heart and liver. Variable effects of Al exposure were observed on temperature kinetic properties of cholinesterases. Altogether these findings indicate that long-term Al feeding results in inhibition of AChE, while an opposite effect is observed on BChE. Decreased Vmax of the brain AChE could represent the mode of action through which Al may contribute to pathological processes in Al-induced neurotoxicity. [Copyright &y& Elsevier]