Studying the Bioactive Components and Phytochemicals of the Methanol Extract of Rhanterium epapposum Oliv.

Rhanterium epapposum Oliv. (locally known as Al-Arfaj) belongs to the family Asteraceae. This study was designed to discover the bioactive components and phytochemicals of the methanol extract of the aerial parts of Rhanterium epapposum, using Agilent Gas Chromatography-Mass Spectrometry (GC-MS), while the mass spectra of the compounds found in the extract matched with the National Institute of Standards and Technology (NIST08 L). GC-MS analysis of the methanol extract of Rhanterium epapposum aerial parts showed presence of sixteen compounds. The major compounds among these were 9,12,15-octadecatrienoic acid, (Z, Z, Z)- (9.89), n-hexadecenoic acid (8.44), 7-hydroxy-6-methoxy-2H-1-benzopyran-2-one (6.60), benzene propanoic acid, ß-amino-4-methoxy- (6.12), 1.4-isopropyl-1,6-dimethyl-1,2,3,4,4 a,7,8,8a-octahedron-1-naphthalenol (6.00), 1-dodecanol, 3,7,11-trimethyl- (5.64), and 9,12-octadecadienoic acid (Z, Z)- (4.84), whereas the minor compounds were 9-Octadecenoic acid, (2-phenyl-1,3-dioxolan-4-yl)methyl ester, trans- (3.63), Butanoic acid (2.93), Stigmasterol (2.92), 2-Naphthalenemethanol (2.66), (2,6,6-Trimethylcyclohex-1-phenylmethanesulfonyl)benzene (2.45), 2-(Ethylenedioxy) ethylamine, N-methyl-N-[4-(1-pyrrolidinyl)-2-butynyl]- (2.00), 1-Heptatriacotanol (1.69), Ocimene (1.59), and ß-Sitosterol (1.25). Furthermore, the study was extended to determine the phytochemicals in the methanol extract of Rhanterium epapposum, which indicated the positive presence of saponins, flavonoids, and phenolic compounds. Moreover, quantitative analysis revealed the presence of high content of flavonoids, total phenolic, and tannins. This study outcome suggests a podium of using Rhanterium epapposum aerial parts as a herbal remedy for various diseases especially cancers, hypertension, and diabetes.

Salvia officinalis L. Methanolic Extract Reduces Lead and Nicotine-Induced Sperm Quality Degeneration in Male Rats.

Most heavy metals and industrial chemicals such as nicotine and lead cause harm to the reproduction process through a decrease in sperm motility, fertilization process, and sperm binding to the oocyte. Salvia officinalis L. (sage) has been reported to enhance serum testosterone levels and other certain biochemical enzymes. Thus, the current study is aimed at evaluating the potential health benefits of S. officinalis L. methanol extract on lead and nicotine hydrogen tartrate-induced sperm quality degeneration in male rats and also identifying some of the non-polar volatile bioactive compounds that might be attributed to the bioactivity of S. officinalis extract using gas chromatography-mass spectrometry (GC/MS). In the study, fifty-four mature male albino rats of about 220-250 g [were divided randomly and equally into 9 groups (n=6)]. Sperm quality degeneration was induced through the oral administration of 1.5 g/L of lead acetate in drinking water or peritoneal injection of 0.50 mg/kg (animal weight) nicotine hydrogen tartrate for sixty days. Two doses (200 & 400 mg/kg b.w.) of S. officinalis L. were used. The rats were anesthetized after the experimental period and then sacrificed. Blood samples were collected while the epididymis, testicle, and accessory sex organs (prostates and seminal vesical) were taken for histopathological studies. Twelve major compounds were identified through the GC/MS analysis of S. officinalis L. methanol extract. Lead and nicotine toxicity had a great effect on the rats' sperm quality causing a significant (p<0.05) decrease in the quantity of sperm and sperm motility as well as an upsurge in the abnormalities of the sperm and a reduction in the length & diameter of seminiferous tubules and size & weight of sexual organs (accessory sex glands, epididymis, and testis). The administration of S. officinalis L. methanol extract, however, had a positive impact on the sexual organ weights, semen quality & quantity, and rats' fertility, thus, ameliorating the adversative effects of both lead and nicotine. Further evaluation and isolation of the bioactive components are recommended as potential drug leads.

Assessment of Bioactive Phytochemicals and Utilization of Rosa canina Fruit Extract as a Novel Natural Antioxidant for Mayonnaise.

The oxidation of food emulsions causes rancidity, which reduces their shelf life. To prevent rancidity, synthetic antioxidants are widely used in the food industry. However, due to their potential health risks, researchers are exploring natural alternatives. This study aimed to investigate whether Rosa canina fruit extract (RCFE) could be used as a natural antioxidant to extend the shelf life of mayonnaise. Mayonnaise containing varying concentrations of RCFE [0.125% (T1), 0.25% (T2), 0.50% (T3), 0.75% (T4)] was compared to a mayonnaise control sample (C1) and a mayonnaise sample containing 0.02% BHT (C2) for 60 days of storage at 4 °C. RCFE was found to have high levels of total phenols content (52.06 ± 1.14 mg GAE g-1), total flavonoids content (26.31 ± 1.03 mg QE g-1), and free radical scavenging activity. The GC-MS analysis of RCFE revealed 39 different peaks, whereas the HPLC analysis showed the presence of 13 polyphenolic compounds in RCFE. The pH values of T2, T3, and T4 mayonnaise samples substantially declined as storage progressed; however, the reduction was less than that of C1 and C2. After 60 days, mayonnaise samples T2, T3, and T4 had greatly reduced peroxide and free fatty acid levels compared to C1 and C2. The mayonnaise enriched with RCFE (T3 and T4) had the most potent antioxidative ability and the lowest value of lipid hydroperoxides (peroxide value, POV) and the lowest value of thiobarbituric-acid-reactive substances (TBARS). The sensory evaluation revealed that the T3 sample exhibited the highest overall acceptability. In conclusion, this study recommends that RCFE could be used as a natural preservative to enhance the shelf life of functional foods.

Ameliorative effect of methanolic extract of Tribulus terrestris L. on nicotine and lead-induced degeneration of sperm quality in male rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of herbal and medicinal plants to treat male infertility is well known in history. Tribulus terrestris L. (TT) belongs to the Zygophyllaceae family and it is used in folk medicine to vitalize and also improve both physical performance and sexual function in men in addition to the protective effect of the gross saponins of TT against ischemic stroke and its clinical anti-inflammatory property. AIM OF THE STUDY: This study aimed to investigate the effects of methanol extract of T. terrestris on nicotine hydrogen tartrate and lead-induced degeneration of sperm quality in male rats and to identify the volatile bioactive non-polar compounds thought to be responsible for its activity using gas chromatography-mass spectrometry (GC-MS). MATERIALS AND METHODS: The effect of T. terrestris on nicotine hydrogen tartrate and lead-induced infertility was evaluated in male rats. Fifty-four mature male albino rats weighing 220-250 g body weight were used. The rats were randomly divided into 9 equal groups (n = 6). Infertility was induced by administering nicotine hydrogen tartrate (0.50 mg/kg) through peritoneal injection (i.p.) or lead acetate (1.5 g/L) orally with drinking water for sixty days. Two doses (50 and 100 mg/kg body weight of the animal) of T. terrestris were also used. At the end of the experimental period, the rats were anesthetized and sacrificed. Blood samples were collected. Hormonal analyses were carried out on the serum. The testicle, epididymis, and accessory sex organs (seminal vesical and prostates) were removed for histopathological analysis. Gas chromatography-mass spectrometry (GC-MS) analysis of the methanol extract was also carried out to identify major volatile compounds in T. terrestris methanol extract. RESULTS: Nicotine and lead toxicity caused a significant (p < 0.05) decrease in the number of sperm, motility, and an increase in the sperm abnormalities such as the reduction in weight and size of sexual organs (testis, epididymis, and accessory sex glands), reduction of diameter and length of seminiferous tubules. The administration of T. terrestris methanol extract, however, improved the semen quantity and quality, sexual organ weights, and fertility of male rats and, thus, ameliorated the adverse effects of nicotine and lead. Ten major compounds were found from the GC-MS analysis of the extract of T. terrestris methanol extract. CONCLUSION: Findings showed that T. terrestris plant methanolic extracts ameliorated nicotine hydrogen tartrate and lead-induced degeneration of sperm quality in male rats. The GC-MS analysis of the T. terrestris plant methanolic extracts revealed the presence of several important bioactive compounds which were thought to be responsible for the ameliorative effect. Further isolation and evaluation of the individual components would provide relevant lead to finding new drugs.

Anti-inflammatory drug approach: Synthesis and biological evaluation of novel pyrazolo[3,4-d]pyrimidine compounds.

In this study, the acid chlorides of pyrazolo[3,4-d]pyrimidine compounds were prepared and reacted with a number of nucleophiles. The novel compounds were experimentally tested via enzyme assay and they showed cyclooxygenase-2 inhibition activity in the middle micro molar range (4b had a COX-1 IC50 of 26 µM and a COX-2 IC50 of 34 µM, 3b had a COX-1 IC50 of 19 µM and a COX-2 IC50 of 31 µM, 3a had a COX-2 IC50 of 42 µM). These compounds were analyzed via docking and were predicted to interact with some of the COX-2 key residues. Our best hit, 4d (COX-1 IC50 of 28 µM, COX-2 IC50 of 23 µM), appears to adopt similar binding modes to the standard COX-2 inhibitor, celecoxib, proposing room for possible selectivity. Additionally, the resultant novel compounds were tested in several in vivo assays. Four compounds 3a (COX-2 IC50 of 42 µM), 3d, 4d and 4f were notable for their anti-inflammatory activity that was comparable to that of the clinically available COX-2 inhibitor celecoxib. Interestingly, they showed greater potency than the famous non-steroidal anti-inflammatory drug, Diclofenac sodium. In summary, these novel pyrazolo[3,4-d]pyrimidine analogues showed interesting anti-inflammatory activity and could act as a starting point for future drugs.

Achillea fragrantissima, rich in flavonoids and tannins, potentiates the activity of diminazine aceturate against Trypanosoma evansi in rats.

OBJECTIVE: To evaluate activity of methanol extract of Achillea fragrantissima (meth) (A. fragrantissima) alone or in combination with diminazine aceturate (DA) against Trypanosoma evansi (T. evansi) in experimentally infected rats. METHODS: Sixty adult male Wister albino rats were divided equally into 6 groups (A-F). Rats in groups A-E were experimentally infected with T. evansi and those in group F were uninfected. The groups were treated respectively as follows: group A-with 3.5 mg/kg DA; group B- with 1000 mg/kg meth A. fragrantissima; group C-3.5 mg/kg DA plus 500 mg/kg meth A. fragrantissima; group D-3.5 mg/kg DA plus 1000 mg/kg meth A. fragrantissima. Group E was left untreated. Parasitemia, survivability, packed cell volume, hemoglobin concentration, total leucocytes count, lymphocyte count, and serum malondialdehyde and reduced glutathione (GSH) levels were estimated. Phytochemical screening of meth A. fragrantissima was also performed. RESULTS: The phytochemical analysis of the meth A. fragrantissima indicated a higher content from polyphenolic tannins and non tannins and flavonoids. The efficacy percentage against trypanosomiasis in groups A - E was respectively as follows 80, 40, 90, 100, 0. The administration of meth-A. fragrantissima (1000 mg/kg b.wt.) produced a moderate efficacy against trypanosomiasis. Untreated rats in group E died between 25 and 30 d post infection. The rats given DA and meth A. fragrantissima combinations (C and D) showed faster and higher recovery rates than the uninfected control and groups A and B. The initial reduction in packed cell volume, hemoglobin, total leucocytes count, increases in serum malondialdehyde and decreases in GSH levels were reversed by the treatments. CONCLUSION: The administration of the methanol extracts of A. fragrantissima and DA combination therapy was more effective than each product alone in the treatment of rats infected with T. evansi and further studies are required to isolate more active ingredients.

Synthesis and biological evaluation of some novel thieno[2,3-d] pyrimidine derivatives as potential anti-inflammatory and analgesic agents.

A novel series of thienopyrimidine derivatives bearing various substituents or linked to various heterocyclic moieties through atoms spacers were prepared starting from 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6- carboxamide potassium salt 3. Twelve out of the prepared compounds were selected and evaluated for their antiinflammatory activity using the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays using diclofenac sodium as a reference standard. The ulcerogenic effects and acute toxicity (ALD50) values of these compounds were also determined. In addition, the analgesic activity of the same compounds was evaluated using the rat tail withdrawal technique. The results revealed that compounds 5a, 13, 14b, 15a, 16a and 16b had high anti-inflammatory effect comparable to diclofenac sodium, whereas compounds 5a, 14a, 15a and 16a revealed pronounced analgesic activity that is equal or higher than that of the reference. All of the tested compounds revealed high GI safety profile and were well tolerated by the experimental animals with high safety margin (ALD50 > 3.0g/Kg).

Design, synthesis and molecular docking study of some substituted 4,5- dihydro-2H-indazole derivatives as potential anti-inflammatory agents.

A new series of 4,5-dihydro-2H-indazoles was synthesized and evaluated for anti-inflammatory activity using formalin-induced paw edema and turpentine oil-induced granuloma pouch bioassays. In addition, the inhibitory activity of cyclooxygenase, ulcerogenic effect, and acute toxicity (ALD50) values were also determined. Compounds 10, 13, 15, 16, 18 and 22 were proved to display distinctive anti-inflammatory profiles with a fast onset of action. They revealed super GI safety profile and are well tolerated by the experimental animals with high safety margin (ALD50 >300 mg/Kg). The same active compounds exhibited moderate to powerful selectivity profile towards the inhibition of COX-2 enzyme. Docking poses for the most active compounds separately in the active site of human COX-2 enzyme were also obtained.

Design, synthesis and biological evaluation of some novel thienopyrimidines and fused thienopyrimidines as anti-inflammatory agents.

Some new substituted thienopyrimidine derivatives comprising thioxo, thioalkyl and pyrazolyl derivatives as well as fused thienotriazolopyrimidine and thienopyrimidinotriazine ring systems were prepared from 3-benzyl-2-hydrazino-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamide 4. The designed compounds were evaluated for their anti-inflammatory activity. Compounds 4, 9, 10 and 13 showed the highest anti-inflammatory effect compared with the reference drug diclofenac sodium.

Teratogenic and cytogenetic effects of ivermectin and its interaction with P-glycoprotein inhibitor.

Experiments in animals proved that P-glycoprotein (Pgp) forms a functional barrier between maternal and fetal blood circulation in the placenta, thus protecting the fetus from exposure to xenobiotics during pregnancy. In this study we aimed to demonstrate the effects of administration of ivermectin (anthelmentic drug, Pgp substrates), either alone or simultaneously with verapamil (Pgp inhibitor) in Wister rats on fetal development, maternal bone marrow for detection of micronuclei (MN), chromosomal aberrations and mitotic index (MI) and embryonic liver cells for cellular proliferation indicated by MI, and bleeding from umbilical vessels for detection of embryonic micronuclei (MN). The results revealed that administration of ivermectin or verapamil at 6th through 15th day of gestation did not significantly altered fetal development. While, co-administration of ivermectin and verapamil clearly disturbed fetal development as indicated from abnormal feto-maternal attachment and a significant decrease in fetal weights and numbers. Furthermore, co-administration of both drugs induced a significant increase in resorption sites, post-implantation loss and external, visceral and skeletal abnormalities. They also induced genotoxicity in both dam and embryonic cells indicated by reduced mitotic index, increased number of micronucleated erythrocytes in both, and increased different types of chromosomal aberrations in dam cells, while ivermectin alone show some genotoxic effect on somatic cells of dams and the embryos. Verapamil induced reduction of embryonic mitotic index. We concluded combined treatment of ivermectin and verapamil severely affect fetal genetic material and development and induced genotoxic effect in somatic cells of the dams.

Grape seed extract prevents azathioprine toxicity in rats.

Azathioprine (Aza) is an important drug commonly used in the therapy of autoimmune system disorders. It induces hepatotoxicity and hazard effects that restrict its use. The effects of administration of grape seed extract and folic acid on Aza toxicity by gavage (simultaneously) daily for 4 weeks were studied by determining the changes in some hematological parameters and liver histology. The glutathione level (GSH) and lipid peroxidation content as malondialdehyde (MDA) in the liver tissue were measured. The repeated intake of Aza (25 mg/kg body weight) induced anemia characterized by decreased erythrocyte and leukocyte counts and reticulocyte and hematocrit percentages, while the prothrombin time was significantly increased. Moreover, Aza caused a significant decrease in phagocytic activity and lymphocyte percentage. Aza induced hepatic damage as indicated by pronounced changes in the histological structure, a significant increase in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), and MDA content in the liver tissue. Meanwhile, the GSH activity was significantly decreased. Co-treatment with grape seed extract and Aza minimized the previously mentioned hazard effects of Aza and significantly protected the hepatic tissue by ameliorating the antioxidant activity. Folic acid administration, simultaneously, with Aza only improved the anemia. It may be concluded that grape seed extract is a useful herbal remedy, especially for controlling oxidative damages and is considered as a potent protective agent against Aza hepatotoxicity.

Synthesis and biological evaluation of novel pyrazolyl-2,4-thiazolidinediones as anti-inflammatory and neuroprotective agents.

Novel pyrazolyl-2,4-thiazolidinediones were prepared via the reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinediones and substituted benzyl-2,4-thiazolidinediones. The resultant compounds were first evaluated for their anti-inflammatory and neuroprotective properties in vitro. The active compounds were further studied in vivo by using the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays. We identified four novel compounds that showed protective effects in vitro at non-toxic concentrations, and were also effective in the animal models of acute and sub-acute inflammation.

Design and synthesis of some thiazolyl and thiadiazolyl derivatives of antipyrine as potential non-acidic anti-inflammatory, analgesic and antimicrobial agents.

The synthesis of two groups of structure hybrids comprising basically the antipyrine moiety attached to either polysubstituted thiazole or 2,5-disubstituted-1,3,4-thiadiazole counterparts through various linkages is described. Twelve out of the newly synthesized compounds were evaluated for their anti-inflammatory activity using two different screening protocols; namely, the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays, using diclofenac Na as a reference standard. The ulcerogenic effects and acute toxicity (ALD(50)) values of these compounds were also determined. Meanwhile, the analgesic activity of the same compounds was evaluated using the rat tail withdrawal technique. Additionally, the synthesized compounds were evaluated for their in vitro antimicrobial activity. In general, compounds belonging to the thiazolylantipyrine series exhibited better biological activities than their thiadiazolyl structure variants. Collectively, compounds 6, 10, 26, and 27 proved to display distinctive anti-inflammatory and analgesic profiles with a fast onset of action. All of the tested compounds revealed super GI safety profile and are well tolerated by the experimental animals with high safety margin (ALD(50)>3.0 g/kg). Meanwhile, compounds 7, 10, 11, and 23 are considered to be the most active broad spectrum antimicrobial members in this study. Compound 10 could be identified as the most biologically active member within this study with an interesting dual anti-inflammatory analgesic and antibacterial profile.

Effects of marjoram volatile oil and grape seed extract on ethanol toxicity in male rats.

Natural dietary antioxidants are extensively studied for their ability to protect cells from miscellaneous damages. Marjoram volatile oil (Origanum majorana L., Lamiaceae) and grape seed extract (Vitis vinifera L., Vitaceae) are potent antioxidants. Effects of administration of marjoram volatile oil or grape seed extract on oral administration of ethanol, simultaneously, daily for 10 weeks were studied through determining epididymal spermatozoal analysis, serum testosterone level, weight and histopathological examination of testis, liver and brain. Glutathione level and lipid peroxidation content as malondialdehyde in the testis, liver and brain were measured. The repeated intake of a great amount of ethanol (10 ml/kg body weight, 25% v/v) was followed by fertility disturbances with low sperm count, impaired sperm motility and decrease in serum testosterone level. Moreover, ethanol toxicity induced significant alterations in the histological structures of the testis, liver and brain. The results revealed a significant increase in lipid peroxidation and decrease in the level of glutathione in the testis, liver and brain in the ethanol-treated group. However, co-administration of the extracts of protective plants resulted in minimizing the hazard effects of ethanol toxicity on male fertility, liver and brain tissues. It may be concluded that marjoram volatile oil and grape seed extract are useful herbal remedies, especially for controlling oxidative damages.

Enhanced food intake after stimulation of hypothalamic P2Y1 receptors in rats: modulation of feeding behaviour by extracellular nucleotides.

The present study was aimed to clarify the role of purinergic signalling in the regulation of ingestion behaviour. The ATP/ADP analogues 2-methylthioATP (2-MeSATP) and adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS) increased the food intake after intracerebroventricular infusion in 18-h food-deprived rats. This effect was abolished by pretreatment with the non-selective P2X/P2Y receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) or the selective P2Y1 receptor antagonist MRS 2179, respectively. The stimulation of food intake mediated by ADPbetaS was also blocked by pretreatment with the nitric oxide synthase (NOS) inhibitor Nw-nitro-L-arginine methylester (L-NAME), as well as with the inhibitor of the soluble guanylyl cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), suggesting that the orexigenic effect seems to be closely related with the ensuing formation of nitric oxide. The immunohistochemical staining indicating a co-localization of P2Y1 receptor- and nNOS-immunoreactivities in a population of neurons in the ventromedial hypothalamic nucleus (VMH) agrees with this assumption. Further experiments with the direct local application of these compounds into the VMH and lateral hypothalamic nucleus (LH) show that the stimulation of P2Y1 receptors in these functionally antagonistic brain regions exerts an increased food intake. Hence, different signal transduction mechanisms may operate in the VMH and LH. Our assumption is supported by distinct effects of the NOS inhibitor L-NAME in these two hypothalamic nuclei. The present data suggest that ATP/ADP, acting as extracellular signal molecules in the rat brain, are involved in the regulation of food intake, possibly depending on P2Y1-receptor-mediated nitric oxide production.

Grape seed extract prevents gentamicin-induced nephrotoxicity and genotoxicity in bone marrow cells of mice.

The protection conferred by grape seed extract against gentamicin-induced nephrotoxicity and bone marrow chromosomal aberrations have been evaluated in adult Swiss albino mice. The activity of reduced glutathione peroxidase (GSH peroxidase), the levels of glutathione (GSH) and lipid peroxidation as malondialdehyde (MDA) in the kidneys homogenates, serum urea and creatinine were measured, and in addition the changes in kidney histology and bone marrow chromosomes were investigated. Gentamicin (80 mg/kg b.wt. intraperitoneally for 2 weeks) induced kidney damage as indicated from a pronounced changes in kidney histology, a significant increase in serum urea and creatinine and MDA content in the kidney homogenate. While the activity of the antioxidant enzyme GSH peroxidase and the level of GSH were significantly decreased. Gentamicin induced genotoxicity indicated by increased the number of aberrant cells and different types of structural chromosomal aberrations (fragment, deletion and ring chromosome) and showed no effect on mitotic activity of the cell. Pretreatment with grape seed extract (7 days) and simultaneously (14 days) with gentamicin significantly protected the kidney tissue by ameliorating its antioxidant activity. Moreover, grape seed extract significantly protected bone marrow chromosomes from gentamicin induced genotoxicity by reducing the total number of aberrant cells, and different types of structural chromosomal aberrations. It could be concluded that grape seed extract acts as a potent antioxidant prevented kidney damage and genotoxicity of bone marrow cells.

Protection by turmeric and myrrh against liver oxidative damage and genotoxicity induced by lead acetate in mice.

The effects of lead acetate in the diet (0.5% w/w) on reduced GSH, activity of phase II metabolizing enzyme glutathione S-transferase (GST), lipid peroxidation in liver homogenate and bone marrow chromosomes of mice simultaneously supplemented with powdered turmeric and myrrh for 8 weeks were investigated. Five groups of Swiss male albino mice, each of 30 mice, the first group received a basal diet and served as negative control, the second group received basal diet supplemented with lead acetate only and served as positive control. The other three groups received basal diet supplemented with lead acetate and 1% or 5% turmeric powder and 1% myrrh powder, respectively. Results revealed a significant decrease in the amount of GSH in all treated groups compared with negative control. Also, the activity of GSH S-transferase was significantly decreased in positive control compared with other groups. However, co-administration of the protective plants resulted in a significant increase in the activity of GST compared with both positive and negative control groups. Furthermore, lipid peroxidation was significantly increased in positive control alone, while co-treatment with the protective plants resulted in reduction in the level of lipid peroxidation by 31% and 49% in mice receiving 1% and 5% turmeric powder respectively and 45% in 1% myrrh treated when compared with their respective positive control group. Lead genotoxicity was confirmed through significant reduction in the number of dividing cells, increased total number of aberrant cells and increased frequency of chromosomal aberrations. Simultaneous treatment with these plants significantly reduced the genotoxicity induced by lead administration and the powerful protection was observed with 5% powdered turmeric. It may be concluded that turmeric and myrrh are useful herbal remedies, especially for controlling oxidative damages and genotoxicity induced by lead acetate intoxication.

Protective effect of volatile oil, alcoholic and aqueous extracts of Origanum majorana on lead acetate toxicity in mice.

Natural dietary antioxidants are extensively studied for their ability to protect cells from miscellaneous damages. Origanum majorana L., Lamiaceae, is a potent antioxidant. The effect of administration of O. majorana (volatile oil, alcoholic and aqueous extracts) on oral administration of lead acetate in the diet of mice at concentration 0.5% (W/W) for one month were studied by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine, histopathological changes of the liver and kidney and genotoxicity including, rate of micronucleus and chromosomal aberrations in bone marrow cells. Mice were treated with the 3 different forms of O. majorana, one month before and maintained with lead acetate administration. The 3 forms of O. majorana induced a significant decrease in serum activities of transaminases (AST & ALT), ALP, urea and creatinine and improved the liver and kidney histology in comparison with lead acetate treated group. Alcoholic extracts of O. majorana significantly reduced the rate of micronucleus, number of aberrant cells and different kinds of chromosomal aberrations. Volatile oil extract significantly reduced the rate of micronucleus and chromosomal fragments. Aqueous extract and volatile oil also of O. majorana significantly reduced number of gaps, ring chromosome and stickiness. It could be concluded that O. majorana plays an important role in ameliorating liver and kidney functions and genotoxicity induced by lead toxicity.

Reproductive and cytogenetic toxicity of metronidazole in male mice.

The purpose of this study was to examine the effects of metronidazole (500 mg/kg b.wt. daily by gavage for 14 consecutive days) on male fertility, haematopoiesis and genotoxic affinity. Mature male Swiss mice were treated with metronidazole and divided into 3 groups each with 10 animals, examined after 2 weeks, 1 and 2 months from the onset of drug administration. The results demonstrated that metronidazole significantly (P<0.05) decreased the weight of the testes, epididymides and accessory sexual organs (seminal vesicles and prostates) after one month from the onset of treatment. While accessory sexual organ weights were restored after 2 months from onset of treatment, the decrease in testes and epididymides weights persisted until 2 months later. The deleterious effects of metronidazole on reproductive organ weights might be due to a decrease in testosterone level after 2 weeks, and 1 and 2 months from the onset of treatment. Metronidazole induced a significant decrease in motile sperm and an increase in abnormal sperm after 1 month. The viability of sperm was normal after 2 months. Metronidazole induced anaemia characterized by decreased erythrocyte and leukocytic counts, haemoglobin content and haematocrit %. The ability of oral metronidazole administration to induce genotoxic damage in somatic cells of mice was evaluated using mitotic index, micronuclei and chromosomal aberration. A significant reduction in mitotic activity was observed two weeks from the onset of drug administration, restoration occurred after one month. A significant and persistence increase in the frequency of chromosomal aberration and micronucleus was observed at all periods of the experiment. In conclusion, the results of this study indicate that 1) metronidazole (500 mg/kg by gavage) for 14 days caused a harmful effect on male fertility in mice after one and two months from start of administration, 2) metronidazole induced anaemia after one month from start of administration, 3) metronidazole at this high dose level (3 times the therapeutic dose in mice) has the ability to induce genotoxic effects in somatic cells.