Gbenga A. Adenuga

Effect of lead exposure on liver lipid peroxidative and antioxidant defense systems of protein-undernourished rats

The effect of the liver mitogen, lead nitrate [Pb(NO3)2], on protein-undernutrition-induced increased lipid peroxidation and reduced antioxidants levels was investigated in rats. Animals were divided into four groups: A, B, C, and D of five animals each. Animals in groups C and D were placed on a low-protein diet (5% casein) and animals in groups A and B were maintained on a normal diet (16% casein) for 14 wk and fed ad libitum. Animals in groups B and D were each given a single intravenous injection of Pb(NO3)2 (100 μmol/kg body weight) 72 h before sacrifice. The results confirm that protein undernutrition (PU) induced an increase in lipid peroxidation with concomitant reductions in catalase (CAT) activity, glutathione (GSH) level, and superoxide dismutase (SOD) activity. Lead (Pb) treatment, however, provoked increased lipid peroxidation, CAT activity, and GSH level but resulted in reduced SOD activity in both normal and PU-rats. These results suggest that Pb exacerbates liver lipid peroxidation in PU rats and suggests the involvement of free radicals in the pathogenesis of Pb poisoning. In addition, the results show that Pb affects well-fed and PU rats in similar ways but that the CAT activity of PU rats is more sensitive to the effect of Pb than that of normal rats.

Postnatal protein malnutrition induces neurochemical alterations leading to behavioral deficits in rats: Prevention by selenium or zinc supplementation

Abstract Background/objectives Protein malnutrition (PM) is a worldwide problem affecting brain development in a large number of children. The present study was aimed at studying the perturbations in antioxidant defense system resulting from protein deficiency and to evaluate the preventive effect of Se and Zn on cortex and cerebellum. Methods Well-fed (WF) and PM rats were fed on 16 and 5% protein diet, respectively. After 10 weeks, animals were supplemented with Se and Zn at a concentration of 0.15 and 227 mg/l in drinking water for 3 weeks. Results PM rats showed significant increase in lipid peroxidation, nitrite, and protein carbonyl levels. Reduction in the activity of antioxidant enzymes, thiol levels, GSH/GSSG ratio, and neurobehavioral deficits were observed in PM groups. Se and Zn supplementation reduced the levels of lipid peroxidation, nitrite, and protein carbonyl and restored the activity of antioxidant enzymes and thiol levels in the cortex and cerebellum of PM rats along with neurobehavioral deficits. Discussion The study showed that Se and Zn supplementation might be beneficial in preventing biochemical alterations and neurobehavioral deficits in PM children.

Protective Effect of Selenium on Protein-Undernutrition-Induced Brain Damage in Rats

The effect of ad libitum ingestion of selenium (Se) in drinking water (0.15 mg SeO2/L) for 3 wk on the brain weight, total brain protein, glutathione (GSH) level, catalase activity, and lipid peroxidation in the brain of protein-undernourished (PU) rats was investigated, in an attempt to determine whether antioxidants alone can reverse some of the neuropathological changes associated with protein undernutrition in rats. Feeding on a normal diet (16% casein) by well-fed rats or a low-protein diet (5% casein) by PU rats and Se-treated PU rats lasted 14 wk. Setreated PU rats were given Se in drinking water during the last 3 wk of the experiment. Results show that protein undernutrition induced significant reductions (p<0.001) in brain weight, total brain protein, and catalase activity (p<0.05) while it induced a significant increase (p<0.05) in lipid peroxidation when compared with well-nourished rats; but no significant effect was observed for the GSH level. However, the ingestion of Se in drinking water by PU rats for 3 wk resulted in significant increases (p<0.05) in brain weight, catalase activity, and total brain protein but induced a significant reduction (p<0.05) in lipid peroxidation when compared with PU rats given water. The values obtained for Setreated PU rats are comparable with those obtained for well-nourished rats. The GSH level was, however, not affected by Se ingestion. We suggest that Se, by inducing increases in the concentration of certain proteins, including catalase, in the brain, abolished some of the pathological changes associated with protein undermutrition in the brain, and appears as a promising antioxidant in the prevention and management of pro-oxidant-induced brain damage.

Comparative study on the influence of fluoride on lipid peroxidation and antioxidants levels in the different brain regions of well-fed and protein undernourished rats.

Effects of fluoride on the levels of Lipid peroxidation (LP) and antioxidant enzymes in the brain regions of protein undernourished (PU) and well-fed rats (WF) rats exposed to 100 ppm fluoride in drinking water were investigated. The results indicate that the mean body weights and the total brain weights of PU rats as well as those given fluoride (both WF and PU) were significantly (P < 0.05) lower than their respective controls. The weights of different brain regions were also significantly reduced (P < 0.05) in PU rats compared to WF rats except in the brain stem. Fluoride ingestion diminished the weights of WF and PU rats affecting the cerebrum only (in the case of PU rats) and the cerebellum of both WF and PU rats without an effect on the brain stem of both WF and PU. Additionally, increased LP was observed in the cerebrum and cerebellum of PU rats but after fluoride ingestion, 30% increase in LP was observed only in the cerebrum. In the brain stem however, protein undernutrition was accompanied with a significant reduction in LP but the region seems insensitive to fluoride. There were significant reductions (P < 0.05) in CAT, SOD and GSH in all the brain regions (except the GSH level in the brain stem only) of PU rats. Fluoride induced reduction in the activity of CAT in the three brain regions and on SOD activity in cerebrum only for WF rats but no effect of fluoride on all the antioxidants studied in the three brain regions for PU rats. It is concluded that WF and PU rats responded differently to fluoride toxicity. However, it seems that at the dosage used, fluoride toxicity may be a direct effect on the antioxidant enzymes.

Protective roles of selenium and zinc against postnatal protein-undernutrition-induced alterations in Ca2+-homeostasis leading to cognitive deficits in Wistar rats

Postnatal protein‐undernutrition impacts on mental development and cognition in children and can lead to problem with attention and unresponsiveness which compromise childrens ability to learn. These behavioral disorders might be due to alteration in calcium homeostasis as calcium plays critical roles in fundamental functions of neuron. The role of low protein diet as well as Se and Zn supplementation on intracellular calcium concentration ([Ca2+]i), Ca2+‐ATPase, Na+‐K+‐ATPase, calpain and caspase‐3 activities from rat cortex and cerebellum were investigated. Well‐fed (WF) and low protein diet‐fed (LPDF) rats were given diets containing 16% and 5% casein, respectively, for a period of 10 weeks. Then, the rats were supplemented with Se and Zn at a concentration of 0.15 mg L−1 and 227 mg L−1, respectively, in drinking water for 3 weeks. The results obtained from the study showed a significant increase in [Ca2+]i; calpain and caspase‐3 activities as well as increase transfer latency in water maze study and reductions in Ca2+‐ATPase and Na+‐K+‐ATPase activities for LPDF rats compared to WF rats. Se and Zn supplementation to LPDF rats reversed the elevation in [Ca2+]i, calpain and caspase‐3 activities and restored the cognitive deficits and the activities of Ca2+‐ATPase and Na+‐K+‐ATPase. Conclusively, protein‐undernutrition results in the accumulation of synaptosomal calcium and inhibition of calcium transporters presumably via free radical generations and results in cognitive impairment which also probably results from neuronal death in rats through calpain activation and the caspase cascade mechanisms. However, Se and Zn supplementations ameliorated the anomalies observed.

The Ca2+-Transporting Activity of Rat Liver Microsomes in Response to Protein Undernutrition: Implications for Liver Tumor Promotion

The effect of protein undernutrition on the activity of the smoothendoplasmic reticulum (microsomal) Ca2+-ATPase (SERCA) wasinvestigated. After 12 weeks of ad libitum ingestion of low proteindiet (5% protein), a significant depression (p<0.05) of liver ERCa2+-ATPase activity (68.6% depression) was observed. However,no significant effects on cytochrome P450 activity and relative liverweight were found. It is proposed that low protein diet by inhibitingthe rat liver SERCA activity, might increase the cytosolic free calciumion concentration ([Ca2+]) and promote the development of livertumor. The possible mechanisms of low protein diet induced inhibition ofSERCA activity are highlighted.

The response of liver lipid peroxidative and antioxidant defense systems of protein undernourished rats to liver regeneration

The response of liver lipid peroxidative and antioxidant defense system of protein undernourished rats to liver regeneration induced by partial hepatectomy was examined in rats. Animals were divided into four groups; A,B,C and D of four animals each. Animals in group A were maintained on 16% casein diet while those in groups B, C and D were placed on low-protein diet (5% casein) for fourteen weeks and fed ad libitum. 72 hours before sacrifice, partial hepatectomy was carried out on animals in group D while animals in group C were sham-operated. The results show that protein undernutrition induced an increase in lipid peroxidation but reduced catalase activity, glutathione level and superoxide dismutase activity when compared with well-nourished rats. Liver regeneration however, resulted in significant increases in lipid peroxidation and catalase activity but significant reductions in glutathione level and superoxide dismutase activity in protein undernutrition rats when compared with their sham-operated counterparts. These results suggest that liver regeneration induced by partial hepatectomy exacerbates lipid peroxidation in protein undernutrition rats and that Catalase plays a major role in the mopping up of reactive oxygen species generated following liver regeneration in partially hepatectomised protein undernutrition rats.

Consequence of Aflatoxin B1 Ingestion on the Membrane-Bound Liver Endoplasmic Reticulum Ca2+-ATPase of Protein-Undernourished Fischer F344 Rats

Ingestion of the mycotoxin Aflatoxin B1 (AFB1) by protein-undernourished Fischer F344 rats for twelve weeks resulted in significant (p<0.05) increases in the proliferation of liver cells, reduced body weight and increased microsomal Ca2+-ATPase activity. Cyt. P450 content, γ -Glutamyl Transferase (GGT) and Glutathione Transferase (GST) activities were unaffected. The ingestion of AFB1 by normal rats had no effect on all the parameters investigated. It appears that the microsomal Ca2+-pumping ATPase of Protein-Undernourished (PU) Fischer F344 rats is more sensitive to the mycotoxin AFB1 than its counterpart in well-nourished rats. The use of PU rat as animal model for studies on AFB1 toxicity, particularly the effect of AFB1 on the regulation of intracellular calcium ion concentration ([Ca2+]i), is suggested.

Dietary Selenium or Zinc Supplementation Restores Brain Lipid Composition and Membrane Fluidity in Protein-Undernourished Rats

Studies have shown that protein undernutrition (PU) modifies the membrane lipid composition in the intestine and liver, as well as in plasma and other areas. However, there is limited information on the effect of PU on synaptosomal membrane lipid composition and fluidity and the protective role of selenium (Se) and zinc (Zn), which is a major focus of the present study. For 10 weeks, rats were fed diets containing 16% casein, which constituted the adequate protein diet, or 5% casein, representing the PU diet. The animals were supplemented with Se and Zn at a concentration of 0.15 and 227 mg L-1, respectively, in drinking water for 3 weeks. The results showed a significant increase in total lipids, glycolipids, triglycerides, cholesterol, and the cholesterol/phospholipid (Chol/PL) ratio, and a significant reduction in phospholipids and membrane fluidity. Se and Zn supplementation to PU rats, however, significantly lowered total lipids, glycolipids, triglycerides, cholesterol, and the Chol/PL ratio, while phospholipids and membrane fluidity were significantly restored. It is concluded that a perturbed lipid composition induced by PU affects the membrane structure and fluidity, which in turn influences membrane functions. The study suggests that Se and Zn supplementation might be beneficial in restoring the lipid dyshomeostasis associated with PU.

Reduced expressions of calmodulin genes and protein and reduced ability of calmodulin to activate plasma membrane Ca(2+)-ATPase in the brain of protein undernourished rats: modulatory roles of selenium and zinc supplementation.

The roles of protein undernutrition as well as selenium (Se) and zinc (Zn) supplementation on the ability of calmodulin (CaM) to activate erythrocyte ghost membrane (EGM) Ca2+‐ATPase and the calmodulin genes and protein expressions in rats cortex and cerebellum were investigated. Rats on adequate protein diet and protein‐undernourished (PU) rats were fed with diet containing 16% and 5% casein, respectively, for a period of 10 weeks. The rats were then supplemented with Se and Zn at a concentration of 0.15 and 227 mg l−1, respectively, in drinking water for 3 weeks. The results obtained from the study showed significant reductions in synaptosomal plasma membrane Ca2+‐ATPase (PMCA) activity, Ca2+/CaM activated EGM Ca2+ATPase activity and calmodulin genes and protein expressions in PU rats. Se or Zn supplementation improved the ability of Ca2+/CaM to activate EGM Ca2+‐ATPase and protein expressions. Se or Zn supplementation improved gene expression in the cerebellum but not in the cortex. Also, the activity of PMCA was significantly improved by Zn. In conclusion, it is postulated that Se and Zn might be beneficial antioxidants in protecting against neuronal dysfunction resulting from reduced level of calmodulin such as present in protein undernutrition. Copyright