Gross intestinal adaptations in relation to broiler performance during chronic aflatoxin exposure.

The present trial was conducted to study some morphological, digestive, and electrophysiological variables of the small intestine during chronic exposure of broilers to aflatoxin B(1) (AFB(1)). Ross 308 male chicks (7 d old) were randomly allotted to control (no AFB(1)), low AFB(1) (0.07 mg of AFB(1)/kg), or high AFB(1) (0.75 mg of AFB(1)/kg) diet. The high AFB(1) diet resulted in reduced (P ≤ 0.002) bird performance during the first 4 wk of exposure, whereas the low AFB(1) diet temporarily reduced (P = 0.034) the bird performance during wk 3 of exposure. During wk 4 of exposure, a linear (P ≤ 0.013) decrease in the unit weight of both the duodenum and jejunum was observed with increasing levels of AFB(1). This reduction in unit weight appeared to progress from the proximal (duodenum) to the distal (jejunum) small intestine with increase in the length of exposure and was not accompanied by modulation of electrophysiological variables in jejunal epithelium. Response from amiloride, a specific blocker of epithelial sodium channel, was also similar among jejunal epithelia of birds under different treatments. Interestingly, a compensatory linear (P ≤ 0.002) increase in the length of the duodenum and jejunum under high AFB(1) diets was noted to occur during wk 4 of exposure. Thus, retention of DM and nitrogen was not negatively affected by the AFB(1) diets. These data indicate that the intestine in broilers may adapt to an ongoing dietary challenge to AFB(1).

Chemopreventive effect of Ginkgo biloba extract against benzo(a)pyrene-induced forestomach carcinogenesis in mice: amelioration of doxorubicin cardiotoxicity.

Ginkgo biloba extract (EGb) is a natural product that possesses antioxidant and anticlastogenic properties. The current study was conducted to investigate the effect of EGb on benzo(a)pyrene (BP)-induced forestomach neoplasia, and to explore its possible beneficial effects against doxorubicin (Dox)-induced cardiotoxicity. Tumor was induced in female Swiss albino mice by oral administration of 1 mg BP, twice weekly for four weeks. EGb was given, at a daily oral dose of 150 mg kg(-1), two weeks before and during BP administration. Dox was given ip at a dose of 1.5 mg kg(-1), once weekly, for four weeks, during BP administration. EGb and Dox were given as combined or monotherapies. Results of the present investigation revealed that EGb blunted forestomach tumor multiplicity, as compared to control tumor bearing group. It also exhibited high activity to induce cytosolic glutathione S-transferase and glucose-6-phosphate dehydrogenase (G6PDH) in liver, as well as replenished hepatic glutathione that have been inhibited or depleted by tumorigenesis. Furthermore, it normalized nitric oxide (NO) serum level, without any observed alteration in neither the activity of liver microsomal NADPH-cytochrome P-450 reductase nor serum level of tumor necrosis factor-alpha (TNFalpha). Similar results have been obtained with Dox, but it failed to affect G6PDH activity, while increased serum TNFalpha and NO levels. The combined therapy did not add further to the anticarcinogenic effect of Dox, however it succeeded in ameliorating the deleterious effects of Dox on the heart; as evidenced by the reduction of cardiac lipoperoxidation, with modulation of Dox-induced pathological changes. Therefore, EGb confers a beneficial chemopreventive effect against BP-induced gastric carcinogenesis in mice, and possesses a salutary ameliorating potential on the cardiotoxic effects of Dox.

Pumpkin-seed oil modulates the effect of felodipine and captopril in spontaneously hypertensive rats.

Natural products like pumpkin-seed oil (PSO) may modify the potency of the calcium antagonist felodipine (FEL) or angiotensin-converting enzyme inhibitor (ACE-inhibitor), captopril (CPT) in modulating the biochemical derangement in blood, heart and kidney as well as blood pressure and heart rate of spontaneously hypertensive rats (SHR) were investigated. SHR were treated orally with FEL at a dose of 0. 45 mg kg(-1) body wt. or CPT at a dose of 9 mg kg(-1) body wt. once daily for 4 weeks. PSO was administered at a dose of 40 mg kg(-1) body wt. alone or with FEL or CPT in the previous respective dose regimen for the same period to SHR. This study showed that hypertension induced increments the content of malondialdehyde (MDA) by 55% and 38% as well as the activity of glutathione peroxidase (GSH-Px) by 26% and 23% in heart and kidney, respectively, accompanied by reductions in the activity of myocardial superoxide dismutase (SOD) from 3.40+/-0.17 to 2.42+/-0.19 U mg protein(-1)and contents of glutathione (GSH) and protein thiols (PrSHs) in different tissues of SHR as compared to normotensive rats. Treatment of SHR with FEL or CPT monotherapy or combined with PSO produced improvement in the measured free radical scavengers in the heart and kidney. Our results also showed that pretreatment of SHR with PSO for 4 weeks then i.v. administration of FEL or CPT produced a significant beneficial hypotensive action. The results were explained in the light of the antioxidant properties of PSO. Therefore, it is concluded that concomitant administration of FEL or CPT with natural antioxidants can yield a beneficial therapeutic effect and retard the progression of hypertension.

Vitamin E protects the brain against oxidative injury stimulated by excessive aluminum intake.

The effect of feeding groups of mice with a diet containing 2000, 4000 and 6000 micrograms aluminum (Al3-/g) for two weeks (subacute) or 2000 and 4000 micrograms Al3+/g for eight weeks (subchronic) as well as the coadministration of vitamin E (alpha-tocopherol) 500 micrograms/g with Al3+, on the status of glutathione (GSH) and lipid peroxides as thiobarbituric acid reactive substances (TBARS) in whole brain tissues were evaluated. Changes in TBARS were further evaluated in vitro following the incubation of brain homogenates of the Al(3+)-fed mice in the presence of 50 microM FeSO4. The results of subacute experiments revealed that the brain levels of GSH were significantly decreased only in the group of mice that received 6000 micrograms Al3+/g diet (P < 0.05) and this effect was partially ameliorated when vitamin E was coadministered with Al3+. TBARS were significantly increased in vitro only in the presence of free iron ions and depended on the concentration of Al3+ in the diet. The effect was opposed by the vitamin E intake. Following subchronic Al3+ intake, the GSH content of the brain was significantly decreased only in the group of mice that received 4000 micrograms Al3+/g diet (P < 0.01), while TBARS were significantly increased in the brain tissues in vivo as well as in the presence of free iron ions in vitro. However, coadministration of vitamin E with Al3+ for eight weeks preserved GSH levels and decreased TBARS in the brain of mice in vivo and in the presence of free iron ions in vitro. It is concluded that the long term administration of vitamin E may prevent Al3(+)-stimulated oxidative injury in the brain.

Efficacy of simvastatin and pumpkin-seed oil in the management of dietary-induced hypercholesterolemia.

Pumpkin-seed oil (PSO), a natural supplement rich with antioxidants and polyunsaturated fatty acids (PUFAs), was given in combination with simvastatin, as antihypercholesterolemic drug, to high cholesterol-fed rabbits, for three weeks. In comparison with normal rabbits, a significant increase of the aortic contractile response to norepinephrine was observed which could be attributed to endothelium dysfunction. In addition, serum levels of total lipids, triacylglycerols, total cholesterol and low density lipoprotein-cholesterol (LDL-C) were increased while phospholipids and high density lipoprotein-cholesterol (HDL-C) were decreased in hypercholesterolemic rabbits. These changes could be related to the predominance of LDL and oxidized-LDL particles caused by high levels of reactive oxygen species during hypercholesterolemia (HC). Treatment with simvastatin modulated most of the altered parameters affected during HC that might be, in part, due to inhibition of cholesterol biosynthesis. While concomitant administration of simvastatin and PSO succeeded to cause marked reduction of the aortic contractile response to norepinephrine and to normalize the most adverse effects observed during HC. These effects were explained by the potentiating effects of simvastatin with antioxidants and essential fatty acids in PSO. On the contrary, serum activities of aminotransferases and creatine phosphokinase were increased with simvastatin treatment but not with the combination therapy in hypercholesterolemic rabbits.

Influence of verapamil on the efficacy of vitamin E in preventing the ischemia-reperfusion-induced biochemical dearrangement in cerebral cortex of rat.

The possibility that verapamil (CAS 52-53-9) may intensify the efficacy of vitamin E in preventing the ischemia-reperfusion-caused biochemical dearrangement in rat cerebral cortex was investigated. A daily injection of vitamin E at i.m. dose of 175 mg/kg b.wt. for 7 days prior to subjecting the rats to 1 h bilateral occlusion of the common carotid arteries followed by reperfusion for another 1 h, moderately diminished the ischemia-reperfusion-induced increase in the activity of lactate dehydrogenase and in formation of conjugated dienes as well as in the conversion of xanthine dehydrogenase-->xanthine oxidase in cerebral cortex of rats. However, concomitant injection of verapamil at i.m. dose of 0.68 mg/kg b.wt. 15 min prior to ischemia-reperfusion together with vitamin E pretreatment afforded an elegant combined therapy that effectively abolished the dearrangement caused by ischemia-reperfusion in the above parameters. These results indicated that the protective efficacy of vitamin E against ischemia/reperfusion-induced biochemical dearrangement in cerebral cortex was intensified by concomitant use of verapamil.

Lipid peroxide, phospholipids, glutathione levels and superoxide dismutase activity in rat brain after ischaemia: effect of ginkgo biloba extract.

The influence of ginkgo biloba extract on the lipid peroxide product (malondialdehyde, MDA), glutathione (GSH) and phospholipids levels as well as superoxide dismutase (SOD, 1.15.1.1) and lactate dehydrogenase (LDH, 1.1.1.27) activities in rat brain after occlusion of common carotid arteries was investigated. Two experimental models were studied: 60 min ischaemia without reperfusion and 60 min ischaemia followed by 60 min reperfusion. Compared to sham-operated animals, ischaemia followed by reperfusion increased cytosolic LDH activity and mitochondrial lipid peroxide content and decreased the superoxide dismutase activity and mitochondrial total phospholipids level. Preischaemic administration of ginkgo biloba extract (150 mg kg-1, p.o.) could normalize the SOD activity of the rat brain. The extract was also able to reduce the lipid peroxide and phospholipids contents of the mitochondrial rat brain. These effects could be explained on the basis of the antioxidant property of ginkgo biloba extract and suggests its beneficial role in the protection against post-ischaemic injury.

Effect of dietary zinc on lipid peroxidation, glutathione, protein thiols levels and superoxide dismutase activity in rat tissues.

Dietary zinc deficiency can cause increased lipid peroxidation while zinc supplementation inhibited this process. The aim of this study was to investigate the effect of dietary zinc on malondialdehyde (MDA) product as an index of endogenous lipid peroxidation, glutathione (GSH) and protein thiols (PrSHs) as well as superoxide dismutase (SOD) activity in rat blood, liver and pancreas. Young male rats were fed a zinc deficient (ZD) basal diet containing congruent to 0.5 ppm zinc or were fed ad libitum (AL) a zinc adequate diet (30 ppm zinc) for 3 weeks. The ZD rats were then fed the basal diet supplemented with either 100 ppm zinc or 1000 ppm zinc for another 3 weeks. The zinc concentration of the investigated tissues reflected the dietary zinc content. Plasma, liver and pancreas MDA measurements from ZD rats revealed significant increases (P < 0.05, < 0.001) as compared to AL control values, the highest increase was in pancreas. ZD rats also displayed significant decreases in their blood and liver GSH content (P < 0.001, < 0.05) and SOD activity (P < 0.001) as well as serum PrSHs (P < 0.001) as compared to AL control values. However, these measurements in pancreas were insignificantly changed except GSH content was significantly increased (P < 0.05). Feeding ZD rats a diet containing 100 ppm or 1000 ppm zinc resulted in a significant reduction of the endogenous MDA formation (P < 0.05, < 0.001) in their tissues with the reversal of changes in the other parameters, so that their levels were nearly restored to AL control values especially in response to 1000 ppm zinc.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats.

Pumpkin-seed oil (PSO), a natural supplement rich with antioxidant ingredients, was given to rats in which arthritis was induced using Freund's complete adjuvant. Its effect was compared with that of indomethacin, as a classical anti-inflammatory agent. Two experimental patterns were studied, an acute phase that was applied only with PSO and a chronic phase applied for both PSO and indomethacin. Compared to normal untreated rats, it was shown that the induction of arthritis caused a decrease in serum sulphhydryl groups, with an increase in serum ceruloplasmin in both phases. Blood glutathione was first elevated in the acute phase, then its level was reduced in the chronic phase. Serum N-acetyl-beta-D-glucosaminidase activity was elevated only at the acute phase, while plasma total proteins and albumin were reduced at the chronic phase. Liver glucose-6-phosphate dehydrogenase activity was markedly increased, while no changes were observed in the levels of liver lipid peroxides and glutathione. These changes in the studied parameters were attributed to the superoxides and free radicals during arthritic inflammation. Administration of PSO succeeded in modulating most of the altered parameters affected during arthritis, especially at the chronic phase. Also, a remarkable inhibition of paw oedema was observed. A similar pattern was obtained upon treatment with indomethacin except that indomethacin markedly elevated liver lipid peroxides levels. Concurrent administration of PSO with indomethacin caused no changes in the parameters studied compared to that induced by treatment with indomethacin alone.

Effect of praziquantel treatment on lipid peroxide levels and superoxide dismutase activity in tissues of healthy and Schistosoma mansoni infected mice.

The elevated levels of lipid peroxide product as malondialdehyde (MDA) in plasma, liver, spleen, intestine and kidney of Schistosome-infected mice were differently ameliorated by treatment with praziquantel (EMBAY 8440, CAS 55268-74-1) (2 x 500 mg/kg body wt.) being nearly normalized in plasma and intestine, moderately improved in liver and slightly affected in spleen and kidney. However, the drug failed to affect the MDA levels in the different organs of healthy mice. Moreover, the increased hepatic superoxide dismutase (SOD) activity in infected mice was normalized while the decreased activities in the other tissues were further decreased than normal values in response to praziquantel treatment. Interestingly, in healthy mice, the drug similarly inhibited SOD activities in blood, spleen and kidney. The specificity of this action remains to be clarified. Possible explanations of these findings are given.

Effect of pretreatment with vitamin E or diazepam on brain metabolism of stressed rats.

The effect of vitamin E (VE) or diazepam (DZ) pretreatment on some carbohydrate metabolic aspects in the brains of stressed rats was studied. DZ and VE were given i.p. at doses of 5 mg/kg body wt for 6 days prior to subjecting the animals to single swimming stress (SSS). Pretreatment of the rats with DZ or VE diminished the stress-induced increases in plasma corticosterone and glucose levels and reversed the decrease due to stress on brain ATP, glucose, glycogen and pyruvate contents. The increase in brain ADP and lactate was brought back to levels which approached the pre-stressed values. Moreover, DZ and VE pretreatments helped in attenuating the stress-induced alteration in brain mitochondrial and cytosolic hexokinase as well as sodium, potassium adenosine triphosphatase (Na+,K(+)-ATPase) activities. The change in these metabolic parameters produced by VE pre-treatment was less than that exhibited by DZ. The effects of VE were explained in light of its antioxidant property in preventing the free radical production and lipid peroxide formation which are important factors in the pathogenesis of stress.