Ali A. Shati

Effects of water extracts of thyme (Thymus vulgaris) and ginger (Zingiber officinale Roscoe) on alcohol abuse

INTRODUCTION Alcohol abuse has many harmful effects on human body. This study aimed to investigate the role of water extracts of thyme (Thymus vulgaris) and ginger (Zingiber officinale Roscoe) as natural product extracts to detoxify the injuries of alcohol abuse on liver and brain of mice. MATERIALS AND METHODS Alcohol at a dose of 1.25 ml/50 ml water was orally administered at the first day of treatment with continuously increase of 1.25 ml per day to the end of experiment (14 days, 0.1 ml/45 g /d). Mice also were orally administered with alcohol and water extracts of thyme and ginger in concentration of 500 mg /kg body weight for 2 weeks. RESULTS The results showed very highly significant increase in nitric oxide and malondialdehyde level in liver and brain and a very highly significant decrease in the total antioxidant capacity and glutathione peroxidase activity in alcoholic group. In addition, the liver function enzymes such as L-gamma-glutamyl transpeptidase and butyryl cholinesterase activities showed very highly significant increase in alcoholic group. In contrast, the water extracts of thyme and ginger showed significant amelioration on these changes both in liver and brain tissues. CONCLUSION The water extracts of thyme and ginger has detoxifying and antioxidant effects. Therefore, it is recommended to use them to avoid alcohol toxicity.

Biochemical and molecular aspects of aluminium chloride-induced neurotoxicity in mice and the protective role of Crocus sativus L. extraction and honey syrup.

Aluminium has been proposed as an environmental factor that may affect several enzymes and other biomolecules related to neurotoxicity and Alzheimers disease (AD). The promising protective effect of aqueous saffron extract and honey syrup on neurotoxicity induced by aluminuim chloride (AlCl(3)) may be derived from their own antioxidant properties. Balb/c and C57BL/6 mice (35-40 g) were injected with AlCl(3), 40 mg/kg/day for 45 days. Each mice strain was divided into four groups: AlCl(3) treated group, AlCl(3) plus water saffron extract group (administered with saffron extract at 200 mg/kg b.w. once a day for the experimental period), AlCl(3) plus honey syrup group (administered with honey syrup at 500 mg/kg b.w. for 45 days). The control group received no treatment. Oxidative stress and antioxidant status were estimated in the brain and differential display was performed for both mice strains to scan the mRNA in the treated and non treated groups. In addition, the up and down regulated genes were isolated, cloned and sequenced. The sequence analysis was performed and compared with the other genes cited on GenBank. The results show that there was a decrease in the activity of the antioxidant enzymes (P≤0.001) such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the AlCl3 groups of both mice strains. The level of brain thiobarbituric acid reactive substances (TBARS) showed a significant increase (P≤0.001) of lipid peroxidation (LPO) in the AlCl(3) groups. There was an indication of carcinogenicity in the AlCl(3) treated group representing an increase in serum tumor markers such as arginase and a-l-fucosidase. More than 350 band patterns were obtained and about 22 different up-down regulated genes were observed. The sequence analysis of the three selected up-regulated genes revealed that they are similar to B-cell lymphoma 2 (Bcl-2), R-spondin and the inositol polyphosphate 4-phosphatase genes (INPP4B), respectively. The R-spondin gene was up-regulated in all examined animals except the control ones but the other two genes were only induced in the animals treated with AlCl(3) and honey syrup. We conclude that the biochemical and molecular studies showed the neurotoxicity of AlCl(3) in the brains of mice. In addition, there was an ameliorative change with saffron extract and honey syrup against AlCl(3) neurotoxicity. The obtained molecular results suggest that AlCl(3) made induction for BCL-W gene, which is an anticancer gene or belongs to the DNA repair system in the brain cells, as well as for R-spondin and inositol polyphosphate 4-phosphatase genes, which help in cell proliferation.

Synergistic effect of black tea and curcumin in improving the hepatotoxicity induced by aflatoxin B1 in rats

Aflatoxin B1 (AFB1) is a toxic compound commonly found as a contaminant in human food. It is carcinogenic due its potential in inducing the oxidative stress and distortion of the most antioxidant enzymes. Since black tea possesses strong antioxidant activity, it protects cells and tissues against oxidative stress. Curcumin (CMN), a naturally occurring agent, has a combination of biological and pharmacological properties that include antioxidant activity. Therefore, the present study was carried out to investigate the possible role of separate and mixed supplementation of black tea extract and CMN in the hepatotoxicity induced by AFB1 in rats. A total of 48 adult male Sprague Dawley rats were randomly divided into eight groups with six rats in each group. Group 1 (normal control) includes rats that received no treatment. Groups 2, 3, and 4 (positive control) include rats that received olive oil, black tea extract, and CMN, respectively. Group 5 includes rats that received AFB1 at a dose of 750 μg/kg body weight (b.w.) dissolved in olive oil. Groups 6, 7, and 8 include rats that received AFB1 along with 2% black tea extract, CMN at a dose of 200 mg/kg b.w., and both black tea extract and CMN at the same previous doses, respectively. After 90 days, biochemical and histopathological examination was carried out for the blood samples and liver tissues. A significant decrease in the antioxidant enzymes and a significant increase in the lipid peroxidation and hydrogen peroxide in the rats treated with AFB1 were observed. Moreover, there were dramatic changes in the liver function biomarkers, lipid profile, and liver architecture. Supplementation of black tea extract or CMN showed an efficient role in repairing the distortion of the biochemical and histological changes induced by AFB1 in liver. This improvement was more pronounced when both CMN and black tea were used together.

Green tea (Camellia sinesis) ameliorates female Schistosoma mansoni-induced changes in the liver of Balb/C mice

This study was designed to assess the effect of green tea, an aqueous extract of Camellia sinensis, on the oxidative stress, antioxidant defense system and liver pathology of Schistosoma mansoni-infected mice. Green tea at concentration of 3% (w/v) was given orally to treated mice as sole source of drinking water from the end of the 4th week to the end of 10th week post-infection; untreated mice were allowed to drink normal water. The data of the studied S. mansoni-infected mice exhibited a suppression of hepatic total antioxidant capacity, superoxide dismutase (SOD), catalase (CAT) activity and glutathione content. The liver lipid peroxidation was deleteriously elevated in S. mansoni-infected mice. The hepatic total protein content, AST and ALT activities were profoundly decreased in the S. mansoni-infected mice. Most hepatocytes were damaged and showed abnormal microscopic appearance with aggressive necrosis. Both total protein and glycogen levels have been greatly reduced as indicated by histochemical examination. The treatment of S. mansoni-infected mice with green tea succeeded to suppress oxidative stress by decreasing the lipid peroxides but failed to significantly enhance the antioxidant defense system and deteriorated changes owing to liver damage and necrosis. In consistence with biochemical data, histopathological and histochemical data indicated that treatment of S. mansoni-infected mice with green tea could ameliorate hepatocytes thus reduce cellular necrosis and partially restore both total protein and glycogen levels. Thus, the study concluded that the green tea suppresses the oxidative stress through its constituent with free radicals scavenging properties rather than through the endogenous antioxidant defense system.

Biochemical and molecular studies on the possible influence of the Brassica oleracea and Beta vulgaris extracts to mitigate the effect of food preservatives and food chemical colorants on albino rats

This study aimed to investigate the biochemical influence of broccoli and beet extracts on selected individual additives NaNO2 or sunset yellow treated rats, in addition to the gene expression of some antioxidant enzymes. Forty-two male rats were assigned to seven groups of six rats in each group. The control group was fed a diet without an additive for four weeks. Group (2) received NaNO2, groups (3) received NaNO2 co-administered with broccoli extract (4) NaNO2 co-administered with beet extracts, Group (5) received sunset yellow, Group (6) received sunset yellow co-administered with broccoli extract, and Group (7) received sunset yellow co-administered with beet extract, for four weeks. At the end of the experiment, blood, liver, kidney, and brain samples were taken for biochemical and/or molecular analysis. The mRNA expression of antioxidant enzymes was determined by reversing transcriptase-polymerase chain reaction (RT-PCR). The obtained results revealed that rats co-administered with beet or broccoli extracts had a significant decrease in serum levels of AST, ALT, ALP, urea, total lipids, and triglycerides, as well as a significant increase in reduced glutathione (GSH), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) enzyme activities, compared to the normal control group. Oral administration of NaNO2 or sunset yellow caused a significant increase in serum levels of AST, ALT, ALP, urea, total lipids, and triglycerides, as well as a significant decrease in GSH, GSH-px, and SOD compared to the positive group. In conclusion, this study showed that broccoli and beet extracts have a protective effect against NaNO2 or sunset yellow in rat treated groups.

Hepatotoxic effect of subacute vincristine administration activates necrosis and intrinsic apoptosis in rats: protective roles of broccoli and Indian mustard

Abstract This study investigated the hepatotoxic effect of long-term vincristine (VCR) administration in rats and to assess if an individual or combined therapy with Indian mustard and broccoli afforded protection. Signs of hepatotoxicity, including altered liver architecture and higher serum levels of ALT and AST, were seen in VCR-treated rats. Concomitantly, the impaired antioxidant potential and higher mRNA levels of IL-12 and IL-4, which are markers of apoptosis, were seen in rat livers. VCR treatment induced hepatocyte apoptosis, shown by the up-regulation of mRNA and protein levels of 53, increased protein levels of cleaved caspase-3 and Bax, and reduced levels of intracellular ATP and BCl-2mRNA and protein. Although individual administration of mustard or broccoli partially ameliorated all these responses, the combined therapy of both extracts resulted in the maximum improvement. Thus, the long-term administration of VCR is hepatotoxic and induces apoptosis; however, the combined therapy of both extracts mitigated these effects.

Xanthohumol protects against renal ischaemia reperfusion (I/R) injury by scavenging ROS and inhibition of JAK-2/STAT-3 inflammatory pathway

Abstract Recent evidence has shown that reactive oxygen species (ROS), inflammation and the activation of JAK/STAT signalling are major pathways in the induction and progression of renal ischaemia/reperfusion (I/R) injury. The protective effect of Xanthohumol (XN) against I/R induced renal injury has not been investigated. Hence, this study aimed to investigate the in vivo effect of XN against renal I/R injury. The rats used in this study were divided into 2 main groups of either 1) sham-operated or 2) subjected to renal I/R, in which each group was further divided into 2 subgroups: treated with oral administration of normal saline or XN (1 mg/kg) for 28 days. Renal function, histology, markers and expression levels of oxidative stress, inflammation and apoptosis were examined. The expression levels of the activated JAK-2/Stat-3 signalling pathway were also assessed. XN treatment in the sham group resulted in a normal response, as seen in the sham operated as control group. However, XN significantly improved renal function and attenuated histological changes by reducing the levels of oxidative stress and lipid peroxidation, inflammatory markers, adhesive molecules and the activity of myeloperoxidase (MPO). Concomitantly, reduced expression levels of activated caspase with a parallel decrease in JAK-1/Stat-3 phosphorylation were also noticed. In conclusion, these findings show, for the first time, a protective effect of XN against renal I/R injury, and the mechanisms of protection involve ROS scavenging and an anti-inflammatory effect mediated by the inhibition of the JAK-2/STAT-3 pathway.

The Role of Matricaria recutita L. and Asparagus officinalis L. against theNeurotoxicity of Diazinon in Rats

Diazinon (DZN) is an organophosphate insecticide used mainly in agriculture and in sheep dips, and is designed as an irreversible acetylcholine esterase inhibitor [1,2]. It is classified as moderately hazardous class-II organophosphate insecticide [3]. Many systems could be affected by organophosphate intoxication are the immune system, urinary system, reproductive system, pancreas and haematological and biochemical changes [4-8]. In addition, showed that neonatal DZN exposure, at doses below the threshold for cholinesterase inhibition has been lasting effects on emotional responses, with preferential effects on males [9,10]. The microsomal enzymes in the liver oxidize DZN are generating more potent acetylcholinesterase inhibitors, such as diazoxon, hydroxydiazoxon and hydroxydiazinon [11]. Diazinon affects mitochondrial membrane transportation in rat liver [12]. Moreover, it interrupts cytochrome P450 system in human liver [13]. Oxidative stress can also be induced by pesticides, either by the overproduction of free radicals or by alteration in antioxidant defence mechanisms, including detoxification and scavenging enzymes [14]. Oxidative stress has been reported to play an important role in the toxicity of various pesticides, including organochlorines, carbamates and pyrethrods [15,16]. The higher oxidative stress in pesticide sprayers is evidenced by increased concentration of plasma and red blood cell thiobarbituric acid reactive substances (TBARS), changes in antioxidant status, and altered activities of cellular enzymes [17]. Treatment of rats with DZN significantly enhances renal lipid peroxidation, which is accompanied by a decrease in the activities of renal antioxidant enzymes (e.g. catalase (CAT), glutathione peroxidise, glutathione reductase (GSH-R), glucose- 6-phosphate dehydrogenase, glutathione-s-transferase (GST) and depletion in the level of glutathione reduced (GSH). In blood, normal erythrocyte function depends on the intactness of cell membrane, which is the target for many toxic factors, including pesticides. Erythrocyte GSH together with glutathione peroxidase (GSH-Px), GSH-R, GST, gamma-glutamyl transferase (γ-GT), superoxide dismutase (SOD) and CAT efficiently scavenge toxic free radicals and are partly responsible for protecting against lipid peroxidation due to acute/chronic pesticide exposure [18]. There is a relationship between pesticide exposure and the decrease of antioxidant enzymes [19]. Oxidative stress and genotoxic effects of DZN were documented through the changes in total antioxidant capacity (TAC), reduced GSH and oxidative DNA damage [20]. Exposure to low-level of pesticides is known to produce a variety of biochemical and molecular changes, some of which may be responsible for the adverse biological effects reported in human and experimental studies. Many studies have reported that DZN can induce molecular changes and alter gene expression. Jamshidi et al. have found that administration of DZN to rats at doses of 60 mg/ kg significantly decreased expression of glutamate dehydrogenase, the key enzyme of Langerhans islet for the secretion of insulin, gene 18- hour post-administration [21]. Other studies showed that DZN had affected the expression of neurotrophic factors that coordinate neuronal cell differentiation and brain assembly [22]. In addition, Timofeeva et al. found that persisting effect of developmental DZN cholinergic and serotonergic neurotransmitter systems and gene expression as well as behavioural function [9]. Matricaria recutita L. (family Asteraceae, commonly known as German chamomile) is one of the most widely used and welldocumented medicinal plants in the world [23]. Chamomile is also