Antioxidant activity of milk protein hydrolysate in alloxan-induced diabetic rats.

We investigated the effects of milk protein concentrate (MPC) and milk protein concentrate hydrolysate (MPCH) as antioxidant agents in rats. Six groups of healthy (non-diabetic) and type-II diabetic rats were used: (1) healthy rats (control), (2) alloxan-induced rats (diabetic control group), (3) healthy rats treated orally with MPC, (4) diabetic rats treated orally with MPC, (5) healthy rats treated orally with MPCH, and (6) diabetic rats treated orally with MPCH. We concluded that treatment with MPC or MPCH reduced the level of thiobarbituric acid reactive substances in healthy and diabetic rats. Treatment with MPC or MPCH improved activities of antioxidant enzymes (catalase, superoxide dismutase, reduced glutathione, glutathione-S-transferase, and glutathione peroxidase) in healthy and diabetic rats. From the present data, we concluded that both MPC and MPCH contain potent antioxidants and could improve the health of rats or other animals with diabetes mellitus.

Aluminum oxide and zinc oxide induced nanotoxicity in rat brain, heart, and lung.

Nanomaterials or nanoparticles are commonly used in the cosmetics, medicine, and food industries. Many researchers studied the possible side effects of several nanoparticles including aluminum oxide (Al2O3-nps) and zinc oxide nanoparticles (ZnO-nps). Although, there is limited information available on their direct or side effects, especially on the brain, heart, and lung functions. This study aimed to investigate the neurotoxicity, cardiotoxicity, and lung toxicity induced by Al2O3-nps and ZnO-nps or in combination via studying changes in gene expression, alteration in cytokine production, tumor suppressor protein p53, neurotransmitters, oxidative stress, and the histological and morphological changes. Obtained results showed that Al2O3-nps, ZnO-nps and their combination cause an increase in 8-hydroxy-2´-deoxyguanosine (8-OHdG), cytokines, p53, oxidative stress, creatine kinase, norepinephrine, acetylcholine (ACh), and lipid profile. Moreover, significant changes in the gene expression of mitochondrial transcription factor-A (mtTFA) and peroxisome proliferator activator receptor-gamma-coactivator-1alpha (PGC-1alpha) were also noted. On the other hand, a significant decrease in the levels of antioxidant enzymes, total antioxidant capacity (TAC), reduced glutathione (GSH), paraoxonase 1 (PON1), neurotransmitters (dopamine - DA, and serotonin - SER), and the activity of acetylcholine esterase (AChE) in the brain, heart, and lung were found. Additionally, these results were confirmed by histological examinations. The present study revealed that the toxic effects were more when these nanoparticle doses are used in combination. Thus, Al2O3-nps and ZnO-nps may behave as neurotoxic, cardiotoxic, and lung toxic, especially upon exposure to rats in combination.

Study of the protective effect of ascorbic acid against the toxicity of stannous chloride on oxidative damage, antioxidant enzymes and biochemical parameters in rabbits.

Stannous chloride (SnCl2) is a reducing chemical agent used in several man-made products. SnCl2 can generate reactive oxygen species (ROS). Therefore, the present study has been carried out to investigate the antioxidant action of l-ascorbic acid (AA) in minimizing SnCl2 toxicity on lipid peroxidation, antioxidant enzyme, and biochemical parameters in male New Zealand white rabbits. Animals were assigned to one of four treatment groups: 0mg AA and 0mg SnCl2/kg BW (control); 40 mg AA/kg BW; 20mg SnCl2/kg BW; 20mg SnCl2 plus 40 mg AA/kg BW. Rabbits were orally administered the respective doses every other day for 12 weeks. Results obtained showed that SnCl2 significantly (P<0.05) induced thiobarbituric acid-reactive substances (TBARS; the marker of lipid peroxidation) in plasma, while the activities of glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT), and the level of sulfhydryl groups (SH-group) were decreased (P<0.05) in blood plasma. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (AlP), acid phosphatase (AcP) and lactate dehydrogenase (LDH) activities were decreased (P<0.05). Stannous chloride significantly (P<0.05) increased the levels of plasma total lipid (TL), cholesterol, triglyceride (TG), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), glucose, urea and total bilirubin. On the other hand, the level of plasma high-density lipoprotein (HDL), total protein (TP), albumin (A) and globulin (G) were significantly (P<0.05) decreased. Ascorbic acid alone significantly decreased the levels of TBARS, lipids and urea, and increased the activities of GST, SOD and CAT, and the levels of SH-group and proteins. While the rest of the tested parameters were not affected. Also, the presence of AA with SnCl2 alleviated its harmful effects on most of the tested parameters. Therefore, the present results revealed that treatment with AA could minimize the toxic effects of stannous chloride.

Acrylamide-induced oxidative stress and biochemical perturbations in rats.

Acrylamide is neurotoxic to experimental animals and humans. Also, it has mutagenic and carcinogenic effects. The present study was carried out to investigate the effects of different doses of acrylamide on some enzyme activities and lipid peroxidation in male rats. Animals were assigned at random to one of the following treatments: group 1 served as control, while groups 2, 3, 4, 5, 6 and 7 were treated with 0.5, 5, 25, 50, 250 and 500 microg/kg body weight of acrylamide, respectively in drinking water for 10 weeks. Acrylamide significantly decreased plasma protein levels and the activity of creatine kinase, while increased plasma phosphatases. The activities of transaminases and phosphatases were significantly decreased in liver and testes, while lactate dehydrogenase did not change compared to control group. Plasma and brain acetylcholinesterase activity was significantly decreased. The concentration of thiobarbituric acid reactive substances, and the activities of glutathione S-transferase and superoxide dismutase in plasma, liver, testes, brain, and kidney were increased in acrylamide-treated rats. On the other hand, results obtained showed that acrylamide significantly reduced the content of sulfhydryl groups and protein in different tissues. The present results showed that different doses of acrylamide exerted deterioration effects on enzyme activities and lipid peroxidation in a dose-dependent manner.

Stannous chloride induces alterations in enzyme activities, lipid peroxidation and histopathology in male rabbit: antioxidant role of vitamin C.

Stannous chloride (SnCl2) is widely used in daily human life to conserve soft drinks, in food manufacturing and biocidal preparations. It had genotoxicity, immunotoxicity, neurotoxicity and oxidative stress. Therefore, the present experiment was carried out to determine the effectiveness of l-ascorbic acid (AA) in alleviating the toxicity of SnCl2 on some enzyme activities and oxidative damage in male New Zealand white rabbits. Six rabbits per group were assigned to 1 of 4 treatment groups: 0 mg AA and 0 mg SnCl2/kg BW (control); 40 mg AA/kg BW; 20 mg SnCl2/kg BW (1/500 LD50); 20 mg SnCl2 plus 40 mg AA/kg BW. Rabbits were orally administered the respective doses every other day for 12 weeks. Liver and kidney specimens were processed for histopathologic studies. Results obtained showed that SnCl2 significantly (P < 0.05) induced free radicals in rabbit liver, testes, kidney, lung, brain and heart. While, the activity of glutathione S-transferase (GST) and the level of sulfhydryl groups (SH-group) were decreased (P < 0.05) in all tested organs except brain and heart. Aspartate aminotransferase (AST) activity was increased (P < 0.05) in liver and decreased in testes, but alanine aminotransferase (ALT) did not change. The activities of alkaline phosphatase (AlP) and acid phosphatase (AcP) were decreased (P < 0.05) in liver, testes, kidney and lung. Also, the activity of acetylcholinesterase (AChE) was significantly decreased in brain and plasma of rabbits treated with SnCl2 compared to control group. Histopathologic studies showed marked changes in hepatocytes as well as proliferation of duct epithelium, dilatation and congestion of blood vessels as well as mononuclear inflammatory infiltrate. The kidney were also severely affected by SnCl2 the Bowman's space was increased, with infiltration of renal parenchyma by mononuclear inflammatory infiltrate and changes in cells lining convoluted tubule. Ascorbic acid alone significantly decreased the levels of free radicals, and increased the activity of GST and the levels of SH groups in tested organs except brain and heart. While, the rest of the tested parameters were not affected. Results showed that AA alleviated the harmful effects of SnCl2. This was proved histopathologically by the great improvement in liver and kidney histology where hepatocytes retained normal architecture with mild dilatation and congestion of blood vessels. Bowman's space of kidney was almost normal, with normal lining of proximal and distal convoluted tubules. In conclusion AA could be effective in the protection against stannous chloride toxicity.

Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats.

The present study was carried out to investigate the effects of onion (Allium cepa Linn) and garlic (Allium sativum Linn) juices on biochemical parameters, enzyme activities and lipid peroxidation in alloxan-induced diabetic rats. Alloxan was administered as a single dose (120 mg/kg BW) to induce diabetes. A dose of 1 ml of either onion or garlic juices/100 g body weight (equivalent to 0.4 g/100 g BW) was orally administered daily to alloxan-diabetic rats for four weeks. The levels of glucose, urea, creatinine and bilirubin were significantly (p<0.05) increased in plasma of alloxan-diabetic rats compared to the control group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline and acid phosphatases (AlP, AcP) activities were significantly (p<0.05) increased in plasma and testes of alloxan-diabetic rats, while these activities were decreased in liver compared with the control group. Brain LDH was significantly (p<0.05) increased. The concentration of thiobarbituric acid reactive substances and the activity of glutathione S-transferase in plasma, liver, testes, brain, and kidney were increased in alloxan-diabetic rats. Treatment of the diabetic rats with repeated doses of either garlic or onion juices could restore the changes of the above parameters to their normal levels. The present results showed that garlic and onion juices exerted antioxidant and antihyperglycemic effects and consequently may alleviate liver and renal damage caused by alloxan-induced diabetes.

Changes in some hematological and biochemical indices of rabbits induced by isoflavones and cypermethrin.

Protective effect of isoflavones on cypermethrin-induced changes in blood hematology, and plasma lipids, lipoproteins, glucose, urea, creatinine, total bilirubin and protein concentrations of male New Zealand White rabbits was studied. Rabbits were orally given sublethal dose of cypermethrin (24 mg/kg BW; 1/100 LD50), while isoflavones (2 mg/kg BW) was given alone or in combination with cypermethrin. The tested doses were given to rabbits every other day for 12 weeks. Results showed that cypermethrin caused a significant (P<0.05) increase in the levels of plasma total lipids (TL), cholesterol, triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL), while the level of high density lipoprotein (HDL) decreased. Isoflavones alone significantly (P<0.05) decreased the levels of TL, cholesterol, TG, LDL and VLDL, and increased HDL, and alleviated the harmful effects of cypermethrin on lipid profiles. Cypermethrin caused a significant (P<0.05) increase in glucose, urea, creatinine and total bilirubin. The concentrations of plasma total protein (TP) and albumin (A) were significantly (P<0.05) decreased in plasma of rabbits treated with cypermethrin, while globulin concentration and A/G ratio were not affected. Results showed that cypermethrin significantly (P<0.05) decreased hemoglobin (Hb), total erythrocytic count (TEC) and packed cell volume (PCV), while total leukocyte count (TLC) increased. Isoflavones alone did not cause any significant change in these parameters, but minimized the toxic effect of cypermethrin. Results demonstrated the beneficial influences of isoflavones in reducing the negative effects of cypermethrin on blood hematology and biochemical parameters of male rabbits.

Biochemical study on the effects of some Egyptian herbs in alloxan-induced diabetic rats.

The present study was carried out to investigate the effects of Lupinus albus, L. (Lupinus termis), family L. leguminosae, Cymbopogon proximus, (Halfa barr), family Gramineae, and Zygophyllum coccineum L. (Kammun quaramany), family L. Zygophyllacae on biochemical parameters in alloxan-induced diabetic rats. A dose of 1.5 ml of aqueous suspension of each herb/100 g body weight (equivalent to 75 mg/100 g b.wt.) was orally administered daily to alloxan-diabetic rats for 4 weeks. The levels of glucose, urea, creatinine and bilirubin were significantly (P<0.05) increased in plasma of alloxan-diabetic rats compared with the control group. In contrast, total protein and albumin were significantly decreased by 25 and 46%, respectively, versus control. Treatment of the diabetic rats with repeated doses of any one of the three herb suspensions could restore the changes of the above parameters to their normal levels after 4 weeks of treatment. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (AlP) activities were significantly (P<0.05) increased in the plasma of alloxan-diabetic rats. However, acetylcholinesterase activity was significantly (P<0.05) decreased in the plasma compared with the control group, whereas, such activity did not change in brain. The activities of AST, ALT and LDH were significantly (P<0.05) decreased in the liver of alloxan-diabetic rats by 58, 21 and 40%, respectively, and such activities increased in testes by 39, 26 and 26%, respectively, compared with the control group. Also, brain LDH was significantly (P<0.05) increased. Treatment of the diabetic rats with the aqueous suspension of the tested herbs restored the activities of the above enzymes to their normal level in plasma, liver and testes. The present results showed that the herb suspensions exerted antihyperglycemic effects and consequently may alleviate liver and renal damage caused by alloxan-induced diabetes.

Effect of dietary zinc deficiency on hematological and biochemical parameters and concentrations of zinc, copper, and iron in growing rats.

Zinc has a wide spectrum of biological activities and its deficiency has been related to various dysfunctions and alterations of normal cell metabolism. The effects of adequate Zn level (38 mg/kg diet, control) and two low levels that create Zn deficiencies (19 mg/kg diet, 1/2 of control and 3.8 mg/kg diet, 1/10 of control) were investigated in growing male and female rats for 10 weeks. This allowed for evaluation of the effects these Zn levels may have on body weight gain, specific organ weights, blood parameters, and serum concentrations of Zn, Cu and Fe. Rats fed Zn-deficient diets gained less (P<0.05) than the control groups. There was increase (P<0.05) in liver and spleen weights, and a decrease (P<0.05) in testes weight. However, brain, kidney, heart, and lung weights were not affected (P<0.05). Hematological parameters that were decreased (P<0.05) by Zn deficiency included hemoglobin (Hb), total erythrocyte count (TEC) and packed cell volume (PCV) with the magnitude being dose-dependent. Serum concentrations of total protein, globulin, glucose, and high density lipoprotein (HDL) also decreased (P<0.05) in a dose-dependent manner. Zn deficiency increased (P<0.05) total leukocyte count (TLC) and concentrations of serum albumin, total lipids, cholesterol, triglycerides and low density lipoprotein (LDL) in a dose-dependent manner. Serum concentrations of urea and creatinine were, however, not affected (P<0.05) by zinc deficiency. Zn-deficient rats had lower serum concentrations of Zn, Cu and Fe. These results showed that Zn deficiency has negative effects on growth rate, specific organ weights, hematological parameters, and serum levels of Zn, Cu and Fe, especially in rats fed the lowest Zn level.

Protective role of ascorbic acid to enhance semen quality of rabbits treated with sublethal doses of aflatoxin B(1).

Aflatoxins are toxic to a wide variety of animals, including man. The antioxidant ascorbic acid (AA) plays an important role in various physiological processes in the body including detoxification of different toxic compounds. The objective of this study was to evaluate the effects of AA on productive and reproductive characteristics of mature male rabbits given two sublethal doses (15 or 30 microg/kg of body weight; every other day) of aflatoxin B(1) (AFB(1)). The experiment lasted 18 weeks and included two periods: a treatment period (first 9 weeks) where the animals were given the tested materials, and a recovery period (second 9 weeks) where all the drugs were withdrawn. Results showed that live body weight (LBW), dry matter intake (DMI), relative testes weight (RTW), and serum testosterone were significantly reduced (P<0.05) by treatment with AFB(1) in a dose-dependent manner, and these effects continued during the recovery period. Aflatoxin treatment also decreased (P<0.05) ejaculate volume, sperm concentration, total sperm output, sperm motility index, and semen initial fructose concentration. The negative effects of aflatoxin on semen characteristics were dose-dependent and continued during the recovery period. Treatment with AA increased (P<0.05) LBW, DMI, RTW, serum testosterone concentration, improved semen characteristics, and alleviated the negative effects of AFB(1). Aflatoxin treatment increased (P<0.05) the numbers of abnormal and dead sperms in a dose-dependent manner, and this effect continued during the recovery period. Treatment with AA alleviated the negative effects of AFB1 during treatment and recovery periods. Results demonstrated the beneficial influences of AA in reducing the negative effects of AFB(1) on production and reproduction of male rabbits.

Effect of some hypoglycemic herbs on the activity of phase I and II drug-metabolizing enzymes in alloxan-induced diabetic rats.

Polycyclic aromatic hydrocarbons (PAHs) and N-nitrosamines (NNA) are mainly activated by cytochrome P450s, and their associated enzyme activities such as aryl hydrocarbon (benzo(a)pyrene) hydroxylase (AHH), N-nitrosdimethylamine N-demethylase I (NDMA-dI), NADPH-cytochrome C reductase, and detoxified by glutathione S-transferase (GST) and glutathione (GSH). The present study shows the influence of Cymbopogon proximus (Halfa barr), Zygophyllum coccineum L. (Kammun quaramany), Lupinus albus (Termis) as herbs capable of inducing hypoglycemia on the activity of the above mentioned enzymes in the liver of diabetic rats. Alloxan was administered as a single dose (120 mg/kg body weight) to induce diabetes and the herbs were administered to diabetic rats as repeated doses for 4 weeks. Alloxan-induced diabetes significantly increased the blood glucose level by 93% compared to the control level. On the other hand, repeated-dose treatments of diabetic rats with Cymbopogon proximus and Lupinus albus are more effective than Zygophyllum coccineum in restoring the elevated blood glucose level to the normal level. Alloxan treatment increased the hepatic activity of cytochrome P450, NADPH-cytochrome C reductase, AHH, NDMA-dI, GST and GSH by 112, 122, 82, 99, 64 and 26%, respectively. These herbs decreased the activity of above mentioned enzymes in the liver of diabetic rats compared to alloxan-treated rats. We conclude that alloxan increased the activity of cytochrome P450 system and that such herbs reduced these activities. The toxic effects of PAHs (e.g. benzo(a)pyrene) and NNA (e.g. N-nitrosdimethylamine) could be increased in the liver of diabetic rats through induction of their corresponding bioactivating enzymes. On the other hand, hypoglycemic herbs could alleviate the deleterious effects of these carcinogens in the liver of diabetic rats since these herbs reduced the hepatic content of cytochrome P450 and other associated enzyme activities compared to the diabetic group. Such alterations in the activity of phase I and II drug-metabolizing enzymes should be considered when therapeutic drugs are administered to diabetic patients since most of drugs are metabolized mainly by the cytochrome P450 system.

Dietary zinc deficiency induced-changes in the activity of enzymes and the levels of free radicals, lipids and protein electrophoretic behavior in growing rats.

Zinc (Zn) is an essential nutrient that is required in humans and animals for many physiological functions, including immune and antioxidant function, growth and reproduction. The present study was conducted to investigate the effects of adequate Zn level (38 mg/kg diet, as a control) and two low levels that create Zn deficiencies (19 mg/kg diet, 1/2 of the control and 3.8 mg/kg diet, 1/10 of the control) in growing male and female rats for 10 weeks. To evaluate the effects of these levels, the concentrations of thiobarbituric acid-reactive substances (TBARS), biochemical parameters and protein pattern were studied. Lipid peroxidation in liver, brain and testes of rats fed Zn-deficient diet was indicated by increased TBARS. Serum, liver, brain and testes glutathione S-transferase (GST) activities were significantly (P<0.05) increased in Zn-deficient rats, the effect was pronounced in rats fed the lowest level of Zn (1/10 of control). The activity of lactate dehydrogenase (LDH) was significantly (P<0.05) increased in liver, brain and testes, but decreased in serum in a dose-dependent manner. Zinc deficiency increased (P<0.05) liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in a dose-dependent manner, while there was no effect on the activity of these enzymes in testes. Zinc deficiency resulted in a significant (P<0.05) decrease in the activity of alkaline phosphatase (AlP) in serum and liver in a dose-dependent manner, but no effect in testes was found. The activity of acid phosphatase (AcP) was not affected in serum, liver and testes. Zn-deficient rats had higher liver concentrations of total lipids (TL), cholesterol, triglyceride (TG), and low density lipoprotein (LDL), while high density lipoprotein (HDL) was significantly (P<0.05) declined in a dose-dependent manner. Brain and serum acetylcholinesterase (AChE) activities were, however, not affected (P<0.05) by Zn deficiency. Protein content in liver, brain and testes showed a significant (P<0.05) decrease in rats fed the lowest level of Zn (1/10 of control). Polyacrylamide gel electrophoresis (native-PAGE) of serum proteins revealed that the intensity of immunoglobulins, serum albumin as well as several peptide bands were decreased in rats fed 1/2 or 1/10 of Zn adequate, i.e. their synthesis was affected and it was pronounced with the lowest level of Zn deficiency (1/10 of control). However, no clear effect on the transferrin was observed in both cases compared to controls. From the results of this study it can be concluded that Zn deficiency exerts numerous alterations in the studied biochemical parameters, protein pattern, and increased lipid peroxidation.

Effect of ascorbic acid and Vitamin E supplementation on semen quality and biochemical parameters of male rabbits.

The objective of this study was to determine the effects of supplementation of ascorbic acid, Vitamin E (Vit. E) and their combination in drinking water on sperm characteristics, lipid peroxidation (LPO) and seminal plasma enzymes of mature male rabbits. Twenty-four male New Zealand White rabbits (5 months old) were given drinking water supplemented with ascorbic acid (1.5 g/l), Vit. E (1.0 g/l) and ascorbic acid+Vit. E (1.5+1.0 g/l) for 12 weeks. Vitamin supplementation in drinking water increased feed intake, but body weight gain was not significantly affected. Concentrations of thiobarbituric acid-reactive substances (TBARS) were significantly (P<0.05) reduced in seminal plasma of treated groups compared with the control. Treatment with ascorbic acid, Vit. E, and their combination significantly (P<0.05) increased lipido (reaction time), ejaculate volume, sperm concentration, total sperm output, sperm motility index, total motile sperm, packed sperm volume, initial hydrogen ion concentration (pH), and semen initial fructose concentration. Abnormal and dead sperm were significantly (P<0.05) decreased in treated animals. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were significantly (P<0.05) decreased, whereas glutathione S-transferase (GST) showed a significant increase in seminal plasma of treated animals compared with the controls. The results from this study indicated that supplementation of drinking water with antioxidant ascorbic acid, Vit. E and their combination reduced the production of free radicals and can improve rabbit semen quality, but the greater improvement seemed to be from Vit. E.

Changes of drug metabolizing enzymes in the liver of male sheep exposed to either cypermethrin or dimethoate.

Xenobiotics such as insecticides are metabolized to more or less toxic metabolites by drug-metabolizing enzymes including cytochrome P450 (Cyp P450), cytochrome b5 (Cyp b5), NADPH-cytochrome c reductase (Cyt.c R), N-nitrosdimethylamine-N-demethylase I (NDMA-dI), glutathione (GSH), glutathione s-transferase (GST), and glutathione reductase (GR). Therefore, the present study showed the influence of oral administration of cypermethrin (6 and 12 mg/kg/day) and dimethoate (1.6 and 3.2 mg/kg/day) for 63 consecutive days on the activities of the above mentioned enzymes in the livers of male sheep. Low and high-treatments of sheep with cypermethrin significantly increased the levels of Cyp P450 by 56% and 98%, Cyp b5 by 65% and 80%, GSH by 68% and 74%, and Cyt.c R by 67% and 98%, respectively in a dose-dependent manner. However, low dose of cypermethrin increased the activities of GST and GR by 56% and 91% respectively. In addition, low and high dose-treatments with dimethoate increased the hepatic contents of Cyp P450 by 27% and 40%, GSH by 259% and 132%, whereas NDMA-dI decreased by 27 and 55% respectively, and no change in the content of Cyp b5 and the activity of Cyt.c-R at any given dose of this compound. It is concluded that exposure to cypermethrin and dimethoate significantly changed the hepatic activity of phases I & II drugmetabolizing enzymes in sheep, and these changes are mainly dependent on the administred dose, and also on the type of the tested insecticides. Also, such changes should be considered when therapeutic drugs administered to people exposed to such insecticides.

Protective effect of grape seed proanthocyanidin extract against oxidative stress induced by cisplatin in rats.

Cisplatin is one of the most potent chemotherapeutic antitumor drugs. Oxidative stress has been proven to be involved in cisplatin-induced toxicity. Therefore, the present study was undertaken to examine the antioxidant potential of grape seed proanthocyanidin extract (GSPE) against the toxicity of cisplatin in male rats. Cisplatin treated animals revealed a significant elevation in plasma, heart, kidney and liver thiobarbituric acid reactive substances (TBARS), while the activities of antioxidant enzymes (GST, SOD, CAT and GSH-Px, and the levels of glutathione (GSH) were decreased. Aspartate and alanine transaminases (AST and ALT), creatine kinase and lactate dehydrogenase were significantly increased in plasma, while liver AST and ALT were significantly decreased. Cisplatin significantly increased the levels of plasma total lipid, cholesterol, urea and creatinine, and the relative weight of kidney. On the other hand, plasma total protein and albumin, and body weight were significantly decreased. GSPE reduced cisplatin-induced the levels of TBARS in plasma, heart, kidney and liver, TL, cholesterol, urea and creatinine, and liver AST and ALT. Moreover, it ameliorated cisplatin-induced decrease in the activities of antioxidant enzymes, and GSH, total protein and albumin. Therefore, the present results revealed that GSPE exerts a protective effect by antagonizing cisplatin toxicity.

A sensitive serum-free colorimetric assay for the detection of cytotoxic effects of pesticides.

A new method of cell quantification in the Hybritest bioassay is described. This test is based on culturing the hybridoma cell line 1E6 in the serum-free medium RPMI-SR3 and determination of cytotoxicity by growth inhibition. By employing a tetrazolium salt (MTT), the cell number were quantified colorimetrically using an ELISA reader. This assay carried out in microtiter plates saved time, labour and expenses. It was demonstrated that the sensitivity of 1E6 to pesticide toxicity (glyphosate and cypermethrine) was considerably higher in serum-free medium than in serum-containing medium. Furthermore, it is suggested that this assay may represent an alternative to the use of living animals in toxicological experiments.

A new sensitive cell culture test for the assessment of pesticide toxicity.

A new, simple and sensitive cell culture test for the determination of cytotoxicity of pesticides is described. This test is based on assessment of the growth inhibitory effect of pesticides on the rapidly growing mouse hybridoma cell line 1E6 cultivated in a defined serum-free medium (RPMI-SR3). In addition the cytotoxicity in serum-containing medium was investigated. The results showed that the sensitivity of 1E6 cell towards the toxicity of the pesticides; carbofuran, cypermethrin, lindane, glyphosate and 2,4-D was considerably higher in the serum-free medium than in serum-containing medium. Also IC50 values of these pesticides were compared with LD50 values obtained from the literature. The ratio between the in vitro IC50 and the in vivo LD50 showed that the present cell culture test determine the toxicity of low levels of pesticides with much higher sensitivity than tests based on using animals.

Alterations of lipid profile in plasma and liver of diabetic rats: effect of hypoglycemic herbs.

The effect of three species of hypoglycemic herbs (Termis, Halfa barr, or Kammun Quaramany) on the lipid profile was investigated in plasma and liver tissues of diabetic and herbs-treated diabetic rats. This profile includes total lipids (TL), triglycerides (TG), cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL). A dose of 1.5 ml of aqueous suspension of each herb/100 g body weight (equivalent to 75 mg/100 g body weight) was orally administered daily to alloxan-diabetic rats for four weeks. The present study showed 2-fold increase (p<0.05) in the plasma glucose level of diabetic rats, which received alloxan as a single dose of 120 mg/kg body weight, relative to the mean value of control group. This elevated glucose level was restored to its normal level after treatment with any one of the three herbs. Furthermore, the levels of TL, TG, cholesterol, LDL and VLDL were significantly (p<0.05) increased in the plasma and the liver tissues of diabetic rats compared to the control group, whereas HDL level was significantly (p<0.05) decreased. The plasma levels of all above parameters were normalized after treatment of the diabetic rats with Kammun Quaramany. Treatment of diabetic rats with Tennis normalized TG, cholesterol, LDL and VLDL levels, but Halfa barr restored the induced levels of plasma cholesterol, LDL and HDL to their normal levels. On the other hand, treatment with any of the three herbal suspensions could not restore the concentrations of the all tested parameters in the liver. These data demonstrated that the glycemic control of any of the three herbal suspensions was associated with their hypocholesterolemic effects on the hypercholesterolemia of the alloxan-induced diabetic rats. Moreover, the Kammun Quaramany showed the most potent effect.

Protective effects of isoflavone on some biochemical parameters affected by cypermethrin in male rabbits.

Effect of isoflavone on cypermethrin-induced changes in enzyme activities and free radicals was studied in plasma, liver, brain and testes of male New Zealand White rabbits. Rabbits were orally given sublethal dose of cypermethrin (24 mg/kg BW; 1/100 LD50), while isoflavone (2 mg/kg BW) was given alone or in combination with cypermethrin. The tested doses were given to rabbits every other day for 12 weeks. Results obtained showed that cypermethrin significantly (P < 0.05) induced free radicals in plasma, liver, brain and testes. The activities of glutathione S-transferase (GST) (liver, brain and testes), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (liver and testes), and alkaline phosphatase (AlP) (liver) were significantly (P < 0.05) decreased due to cypermethrin administration. Contrariwise, the activities of GST, AST, ALT and AIP were increased in plasma. The activity of acetylcholinesterase (AChE) did not change in plasma and brain of treated rabbits with cypermethrin. Isoflavone alone significantly (p < 0.05) decreased the levels of free radicals in plasma, liver, brain and testes, while did not produce any significant effect on the investigated enzymes. However, isoflavone is able to reverse the changes in enzyme activities due to the effect of cypermethrin. Results concluded that isoflavone confers marked protection against cypermethrin-induced oxidative stress in rabbit's plasma, liver, brain and testes.

Protective role of isoflavones against the toxic effect of cypermethrin on semen quality and testosterone levels of rabbits.

Cypermethrin is considered as one of the endocrine disruptors. Isoflavones play an important role in various physiological processes in the body. It has both estrogenic and antioxidant effects. The objective of this study was to evaluate the protective role of isoflavones (2 mg/kg B.W) on semen quality and plasma testosterone levels of male New Zealand White rabbits given sublethal dose (24 mg/kg BW every other day for 12 weeks) of cypermethrin. Results showed that treatment with cypermethrin caused a significant decreases (P < 0.05) in ejaculate volume, sperm concentration, total sperm output, sperm motility (%), total motile sperm per ejaculate (TMS), packed sperm volume (PSV), semen initial fructose and plasma testosterone. In addition, live body weight (LBW), dry matter intake (DMI) and relative weights of testes and epididymis were decreased. On the other hand, treatment with cypermethrin increased (P < 0.05) the numbers of abnormal and dead sperms, and initial hydrogen ion concentration (pH). Results indicated that the presence of isoflavones together with cypermethrin was capable to minimize its harmful effects. Treatment with isoflavones alone had positive effects on some semen characteristics in spite of it is considered as estrogen-like compound. Since it causes significant increases in libido (by decreasing the reaction time), PSV, sperm motility and TMS, while abnormal and dead sperm were reduced compared to control animals. Meanwhile, isoflavones had no negative effect on ejaculate volume, total sperm output, sperm concentration, initial fructose concentration, pH and plasma testosterone levels. Results demonstrated the beneficial influences of isoflavones in reducing the negative effects of cypermethrin on reproductive characteristics of mature male rabbits. Interestingly, data showed that isoflavones alone caused an improvement in some semen quality and had no negative effects on male fertility, and did not have negative effects on male fertility.