International Journal of

Toxicological and Pharmacological Research

e-ISSN: 0975 5160

p-ISSN: 2820-2651

Peer Review Journal

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1. The Contribution of Administration Techniques Related to Pseudo-Stress in the Preventive Effectiveness of Hesperidin Against Neurobehavioral and Immunological Disorders Induced by an Air Jet Stress in Wistar Rats
Nessaibia Issam, Chouba Ibtissem, Benatoui Rima , Faci Hayette , Boukhris Nadia, Tahraoui Abdelkrim
Aggressors from outside the body appear to alter its equilibrium, usually associated with an adaptive response against an aggressor that remains unknown to the nervous system as it works as a sufficiently intensified stimulus, capable of activating pain centers and evoking memorial trauma. This study was conducted on male Wistar rats, a model of choice for the study of anxiety has shown the importance of non-invasive administration techniques for the treatment by hesperidin, including the oral administration technique. Compared with this administration technique, a month of hesperidin injections (40 mg/kg) did not show enough preventive ability against significant immune and behavioral alterations induced by 2 h of air jet in the cage of the animal identified by the leukocyte formula and elevated T-maze test. This study suggests that unlike oral administration, the handling and pain associated with repeated intra-peritoneal injections cause the generation of a pseudo-stress expressed by a significant increase of the obtained plasma levels of the adrenocorticotropin hormone (ACTH). These immune-endocrine mediations triggered after such a negative contact with the animal (injections) may have side effects on the efficiency of hesperidin by slowing the anxiolytic properties in addition to the less obvious impact of white cells due to the immune resistance to glucocorticoids.

Abstract Online: 4-June-15

2. Effect of Cinnamon Supplementation on Oxidative Stress, Inflammation and Insulin Resistance in Patients With Type 2 Diabetes Mellitus
Surapon Tangvarasittichai, Sawitra Sanguanwong , Chintana Sengsuk, Orathai Tangvarasittichai
We performed a randomized, double blind, placebo controlled trial to investigate the effect of cinnamon supplementation on malondialdehyde (MDA), total antioxidant capacity (TAC), high sensitive-C-reactive protein (hs-CRP), insulin sensitivity and insulin resistance in 49 patients with type 2 diabetes mellitus (T2DM) and 57 T2DM patients were the placebo group. All participants received either cinnamon or placebo identical capsule daily for 60 days study period. At the end of the study, the median of MDA, hs-CRP levels and insulin resistance were significantly decreased (p<0.005) while TAC and insulin sensitivity were significantly increased (p<0.005) with in the cinnamon supplementation group. In placebo group, we found that MDA and hs-CRP levels were significantly increased (p<0.05) and TAC was significantly decreased (p<0.05) while insulin resistance, insulin sensitivity and insulin levels were not significantly different. Supplementation with cinnamon significantly reduced oxidative stress, insulin resistance, inflammation while increased TAC and insulin sensitivity in T2DM patients. Cinnamon supplementation could be considered as an additional dietary supplement option to prevent and regulate underlying diabetic complications.

Abstract Online: 7-June-15

3. Evaluation of Anticancer Activity of Methanol Extract of Monstera deliciosa in EAC Induced Swiss Albino Mice
Pal Prosanta, Chakraborty Mainak , Karmakar Indrajit , Haldar Sagnik , Das Avratanu , Haldar Pallab Kanti
Aim of study: The purpose of the study was to evaluate the antitumor and antioxidant status of methanol extract of Monstera deliciosa (MEMD) on Ehrlich ascites carcinoma (EAC) treated mice. Materials and methods: In vitro cytotoxicity assay has been evaluated by using the trypan blue and MTT assay method. The determination of in vivo antitumor activity was performed by using EAC cells inoculated mice groups (n=12). The groups were treated for 9 consecutive days with MEMD at the doses of 50 and 100 mg/kg b.w. respectively. After 24 h of last dose, half of the mice were sacrificed and the rest were kept alive for assessment of increase in life span. The antitumor potential of MEMD was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters and biochemical estimations. Furthermore, antioxidant parameters were assayed by estimating liver tissue enzymes. Results: MEMD showed direct cytotoxicity on EAC cell line in a dose dependant manner. MEMD exhibited significant (P< 0.05) decrease in the tumor volume, viable cell count, tumor weight and elevated the life span of EAC tumor bearing mice. The hematological profile, biochemical estimations and tissue antioxidant assay were reverted to normal level in MEMD treated mice. Conclusion: Experimental results revealed that MEMD possesses potent antitumor and  antioxidant properties. Further research is going on to find out the active principle(s) of MEMD for better understanding of mechanism of its antitumor and antioxidant activity.

Abstract Online: 10-June-15

4. In vivo Evaluation of Genetic and Systemic Toxicity of Aqueous Extracts of Phyllanthus amarus in Mice and Rats
Bakare A. A., Oguntolu G. O., Adedokun L. A., Amao A. A., Oyeyemi I. T., Alimba C.G., Alabi O. A.
Phyllanthus amarus is a broad spectrum medicinal plant which has received world-wide recognition. However, there are concerns on the efficacy and safety of this plants’ extract when used as medicinal herb. This study was therefore designed to investigate the genotoxicity of aqueous extract of P. amarus using the mouse micronucleus and sperm morphology assays. The potential effects of the extract on histology of the liver, kidney and testis, and blood parameters of rats were also investigated. Five concentrations: 100, 200, 400, 800 and 1600 mg/kg body weight of the extract were utilized and the test animals were orally exposed for ten consecutive days. Distilled water and cyclophosphamide were utilized as negative and positive controls respectively. Compared with the negative control, the extract induced increasing frequency of micronucleated polychromatic erythrocytes and sperm abnormalities at tested concentrations; and this was significant (p<0.05) at some of the tested doses. There was significant (p<0.05) increase in total white blood cell and lymphocyte counts; and significant pathological changes in the liver, kidney and testis of exposed rats. Tannins, resins, cardiac glycolyside and phenols were analysed in the extract. These findings suggest that aqueous extract of P. amarus contained constituents capable of causing systemic and DNA damage in the mouse and rat.

Abstract Online: 11-June-15

5. Effect of Various Extracts of Ocimum sanctum and Vitex negundo on Gastrothylax crumenifer
Priya M N, Darsana U, Sujith S,  Deepa C K., Lucy K M
The anthelmintic activity of methanolic, aqueous and hydro-alcoholic extracts of the leaves Ocimum sanctum and Vitex negundo and the hexane, chloroform and n-butanol fractions of methanolic extract were investigated on the trematode, Gastrothylax crumenifer.  Adult motility assay was used in the study and the results were compared with the standard drug, oxyclosanide. The study was conducted at six different dilutions of extracts viz. 50, 25, 12.5, 6.25, 3.125 and 1.56 mg/ml prepared in tyrodes solution. The Minimum Inhibitory Concentration of various extracts on Gastrothylax crumenifer was calculated by using the serial dilution technique.  The phytochemical analysis of the extracts were done and the acute oral toxicity was assessed in rats. The methanolic extract of Tulsi as well as its chloroform fraction showed maximum potency with MIC of 1.56 mg/ml and the extracts of Vitex negundo were not as potent as Tulsi. On gross examination, the extract treated worms showed shrinkage, loss of motility and were dead in a dose dependent manner. Histopathology of the extract treated amphistomes showed damage to the syncytium and subsyncitium as well as parenchymal cells indicating the activity on the tegument. The extracts showed the presence of flavonoids, tannins and phenolics which may be the cause of anthelmintic activity,producing damage of tegument. None of the extracts showed any toxicity reactions in rats, hence Ocimum sanctum can be a lead for synthesis of a new trematodicidal drug.

Abstract Online: 13-June-15

6. Amelioration Effect of Red Cabbage Extract on Copper-Induced Hepatotoxicity and Neurotoxicity in Experimental Animals
Abeer H. Abdel-Halim, Amal A. Fyiad, Saeed M. Soliman, Mamdouh M. Ali
Copper is an essential transitional metal, which acts as cofactors in enzyme-catalyzed reactions. It can be toxic to biological systems when it exceeds the levels of cellular needs. Red cabbage has a positive impact on human health where it is rich in minerals, vitamins, oligosaccharides, and a number of bioactive substances. The present study aimed to investigate the protective effect of red cabbage extract on copper induced hepato- and neuro-toxicity in experimental animals. Forty-eight male Sprague–Dawley rats divided into 6 groups (n=8 rats). Intoxicated group was injected intraperitoneal (i.p.) with copper sulphate (CuSO4) (3 mg/kg b.w.) 5 days a week for 2 months. The other groups were orally administered with red cabbage extract (200 mg/Kg b. w.) daily for 2 months alone or with CuSo4 (as pre, post and simultaneous treatment). The activity of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and copper level were demonstrated. Furthermore, hepato- and neuro-antioxidant status such as reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), lipid peroxidation (LPO), deoxiribonucleic acid (DNA), protein contents and the activity of brain acetylcholinestrase (AChE) were also estimated. The results revealed that copper administration resulted in significant injury in the liver tissue as manifested by increase in serum ALT, AST and ALP activities with increase in copper level and significant injury in the brain tissues as indicated by decrease in AChE activity associated with histopathological changes in both tissues. Moreover, administration of copper resulted in increased the level of LPO, depletion of GSH, as well as decrease in antioxidant enzyme activity of SOD, CAT in both liver and brain. The administration of red cabbage alone did not produce the previous biochemical or histological alteration. Administration of red cabbage to the animals given copper counteracted the development of full-blown liver and brain toxicities. Treatment with the extract reduced substantially both liver and brain injuries and restored the histological and biochemical parameters of hepatotoxicity and neurotoxicity towards normal. The ameliorative effect of pre-treated group is more pronounced than that of both post and simultaneous treated groups. These results suggest that red cabbage extract has ameliorative effect on copper induced hepato- and neuro-toxicity in rats via suppression of oxidative stress, and this extract may have a chelating effect on copper

Abstract Online: 14-June-15

7. Antihepatotoxic and Free Radical Scavenging Activities of the Methanolic Leaf Extract of Helianthus annuus
Maxwell I. Ezeja, Yusuf N. Omeh, Samuel O. Onoja, Lilian Anusionwu A
Helianthus annuus (L.) is commonly used in folkloric medicine for treatment of different diseases including liver disorders especially hepatitis. The methanolic leaf extract was evaluated for its antihepatotoxic and free radical scavenging activities.  Hepatic toxicity was induced in the rats by single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (10% CCL4 in Olive oil) after overnight fast at the end of treatment period. Three test doses (150, 300 and 600 mg/kg) of Helianthus annuus leaf extract (HAE) and a standard reference drug, silymarin (100 mg/kg) were administered to the rats orally for seven days through gastric gavage. Twenty four hours after, blood was obtained from the rats through heart puncture into sample bottles from where serum was obtained for biochemical analysis. Parameters evaluated included: liver function tests, malondiadehyde (MDA) levels and catalase activities. Also the animals were sacrificed by cervical dislocation after light chloroform anaesthesia and the liver harvested for histopathological studies. The effect of the extract was compared with silymarin and distilled water controls. Helianthus annuus extract at the doses used caused various levels of significant (p < 0.05) reduction of Aspartate aminotransferase (AST), Alanine aminotransferase (AST), Alkaline phosphatase (ALP) and total bilirubin when compared to negative control. The effect of the extract was comparable to silymarin (100 mg/kg). There was no significant difference (p > 0.05) in the total protein of both the extract treated and the untreated rats.  The free radical scavenging activity was demonstrated by the ability of HAE and silymarin to cause dose-dependent and significant (p < 0.05) reduction of MDA and increase in catalase activities of treated rats when compared to the negative control. The protective activity of HAE was confirmed by histopathology in which the extract exhibited various levels of protection of the liver from degenerative changes observed in the untreated rats. In conclusion, the methanolic extract of Helianthus annuus demonstrated significant dose-dependent antihepatotoxic and free radical scavenging activities against carbon tetrachloride-induced hepatotoxicity in rats as evidenced by the biochemical, functional and histological parameters

Abstract Online: 14-June-15

8. Antimicrobial Activity of Mallotus phillipensis and Allophyllus cobbe
Sreedevi R, Sujith S, Suja R S, Anusree G K, Juliet S
The antimicrobial activity of the aqueous and methanolic extracts and their n-hexane, chloroform, n-butanol and water fractions were tested for antimicrobial activity against eleven microorganisms. The agar well diffusion method using Muller Hinton Agar was used for bacteria and SDA for fungi. The lyophilised cultures purchased from MTCC were revived and used for the study. The extracts were diluted to 500, 250, 100, 50, 25, 12.5 and 100, 50, 25, 12.5, 6.25 mg/ml using DMSO/ Tween 80 and 25 microlitres were transferred into pre-inoculated petri plates, incubated for 24hrs in case of bacterium and 48 hours for fungi and the zones of inhibition was measured. The extracts were subjected to phytochemical analysis as well as cute oral toxicity testing in rats at dose rate of 2000 mg/kg. From the results it is evident that the butanol, chloroform and water fractions of methanolic extract of A. cobbe and hexane fraction of M. phillipensis showed maximum inhibition against S. aureus, S. pyogenes and Cryptococcus. There was no activity against any of the gram negative organisms tested. From the study, it could be concluded that the extracts of A. cobbe and M. Phillipensis posses good antimicrobial property without any potent toxicities

Abstract Online: 14-June-15

9. Chemical Compositions, Potential Cytotoxic and Antimicrobial Activities of Nitraria retusa Methanolic Extract Sub-fractions
Amal A. Mohamed, Sami I. Ali, Osama M. Darwesh, Salwa M. El-Hallouty, Manal  Y. Sameeh
Nitraria retusa is an edible halophyte, used for several traditional medicine purposes. In this work, 6 sub-fractions of methanolic extract of N. retusa aerial parts were investigated for their cytotoxic and antimicrobial activities. For cytotoxic activity, the n-hexane (N-He) sub-fraction exhibited the highest cell growth inhibition against human breast carcinoma cells (MCF-7) (98.5±0.7%), followed by hepatocellular carcinoma cells (HEPG-2) (96±0.8%) as compared to the other sub-fractions. For antimicrobial activities, the N-He sub-fraction had the highest antimicrobial activity among all other sub-fractions. Moreover, the N-He sub-fraction at 1000 µg/ml concentration inhibited Escherichia coli and Pasteurella hemolitica growth by 85.4±0.12% and 85.8±0.18%, respectively after 24 h of incubation. Gas chromatography/mass spectrometry (GC/MS) analysis revealed the presence of different compounds in N-He and N-De sub-fractions. The above results revealed that different sub-fractions of N. retusa could be considered as a potential source of compounds with cytotoxic and antimicrobial effects

Abstract Online: 14-June-15

10. Attenuation of CCl4-Induced Hepatic Damage by Curcumin Extract and/or Folic Acid
Reham A. El-Shafei, Mahmoud G. El-Sebaei, Hebatallah Mahgoub, Rasha M. Saleh
The objective of this study was to evaluate the hepatoprotective effects of curcumin, folic acid and their combination on CCl4 induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. As well as the levels of protein kinase B (Akt1), interferon gamma (IFN-γ), programmed cell death-receptor (Fas) and Tumor necrosis factor-alpha (TNF-α) mRNA transcription was analyzed. After 2-weeks of experimental period, Carbon tetrachloride (CCl4) significantly elevated the levels of lipid peroxidation (malondialdehyde;,MDA), cholesterol, low-density lipoprotein (LDL), triglycerides, bilirubin and urea. CCl4 was found to significantly suppress the activity of both Catalase (CAT) and glutathione (GSH) and decrease the level of serum total protein. While, treatment with curcumin and folic acid for 2-weeks significantly reduced the impact of CCl4 toxicity on liver enzymes, AST, ALT and ALP. The overall potential of the antioxidant system was significantly enhanced by curcumin and folic acid supplements, the hepatic superoxide dismutase (SOD) and CAT activities and glutathione peroxidase (GSH-PX) protein level were elevated (P < 0.05). The mRNA transcriptional level of TNF-α and Fas was significantly upregulated in CCl4 group. Such upregulation was not recorded in treated groups. In addition, a downregulation of Akt1 gene expression was detected in CCl4-intoxicated rats. The mRNA transcriptional level Akt1 was markedly restored and clearly upregulated in rats that were treated with the combination of Curcumin and folic acid. The results indicated that curcumin and/or folic acid have a protective effect against acute hepatotoxicity induced by the administration of CCl4 partially through the restoration of AKT1 expression

Abstract Online: 15-June-15

11. Fluoride-Induced Hypercholesterolemia could be Protective in Fluorosis: High Cholesterol Attenuates Fluoride Toxicity in In Vitro and In Vivo Assays
Alpha Raj M, Adilaxmamma K, Muralidhar Y, Nissi Priya M, Sirisha P
Hypercholesterolemia is a consistent finding in fluorosis. The implications of fluoride-induced hypercholesterolemia are not known. In this study, we investigated the effect of high cholesterol on fluoride toxicity in in vitro and in vivo models. In vitro MTT cytotoxicity was carried out on mouse spleenocytes exposed to fluoride (3.75, 7.5, 15 and 30 µM) either in the presence (250 or 500 µM) or absence of cholesterol. Acute oral toxicity was carried out in normal and triton wr-1339 (200mg/Kg i.p ) induced hypercholesterolemic rats using up and down procedure (OECD 425 guidelines) assisted by AOT 425 software. Cholesterol effectively countered the cytotoxicity of fluoride. The half maximal inhibitory concentration (IC50) of fluoride in 250 µM cholesterol (190.23×103 ppm) and 500 µM cholesterol (459.95×103 ppm) was significantly (P<0.05) elevated compared to control (0.052 ppm). Triton WR-1339 induced significant (P<0.05) hypercholesterolemia (222.44±13.55 mg/dL) compared to control (51.92 ± 8.68 mg/dL). In acute oral toxicity test, the LD50 in hypercholesterolemic group was (170.20 mg/kg; 95% CL: 164.00-290.00) significantly (P<0.05) higher than control group (92.00 mg/kg; 95% CL: 54.07-480.00). It is concluded that fluoride induced hypercholesterolemia is a protective response against fluoride toxicity.

Abstract Online: 07-July-15

12. Association of Bacterial Growth in the Oral Cavity between Tobacco Smokers and Tobacco Chewers
Sudha Sellappa, Usha Rajamanickam, Varun Selvaraj, Mohammed RafiqKhan, Sreeja Vijayakumar
Smoking is considered the major risk factor in the prevalence, extent and severity of several oral diseases. Use of tobacco alters the growth of bacteria in the oral cavity. Hence the present study examined the impact of tobacco use and its cessation on the density of oral microbial population. Study includes 90 subjects with age range 25-65 years, categorized as healthy controls (n = 30), smokers (n = 30), and tobacco chewers (n = 30). Oral bacteria in smokers, tobacco chewers, and non-tobacco users were measured using a spectrophotometer after incubation at 37ºC for a 24 h, 36 h and 48 h period. Tobacco users exhibited an increase of bacteria when compared to non-tobacco users/ healthy controls. This study revealed that tobacco chewing has a more significant effect in increasing the oral microbial population than the tobacco smoking and affect the oral hygiene.

Abstract Online: 07-July-15

13. Comparative Evaluation of Urinary Biomarkers of Exposure to Benzene
Reza Ahmadkhaniha, Noushin Rastkari
Benzene, a known human carcinogen is an airborne pollutant of industrial and general environments. Although toxic effects of benzene at high exposures are well documented, the risk for adverse health effects at low levels of benzene exposure remains unknown; therefore identification of sensitive and specific biological markers is necessary for the definition of low benzene level exposure, so in this study a comparative evaluation of urinary biomarkers (urinary trans, trans-muconic acid , S-phenyl mercapturic acid, and unmetabolized benzene ) was carried out in order to characterize the best benzene exposure biomarker. With this aim, 40 policemen engaged in traffic control, 40 gas station workers and 40 occupationally non-exposed persons were investigated. Spot urine samples were obtained prior to and at the end of the work shift from each subject. Mean benzene exposure was 0.35, 0.22 and 0.09 ppm, respectively, with higher levels in gas stage workers than in control group. U-benzene showed a strong exposure-related increase. In conclusion, in the range of investigated benzene exposure, U-benzene is the marker of choice for the biological monitoring of occupational and environmental exposure.

Abstract Online: 30-July-15

14. Suvorexant: A New Drug in the Treatment of Insomnia
Samar Ayub, Sandeep Maharaj, Sureshwar Pandey, Akram Ahmad, Muhammad Umair Khan, Sameer Dhingra
Insomnia is classified as a psychiatric disorder where patients complain of difficulty falling asleep, maintaining sleep, or not feeling rested in spite of a sufficient opportunity to sleep. In today’s stressful society an increase in complaints of insomnia has been noted. Patients have been found trying to source over the counter sleep aids to help with sleepless nights. It has been noted due to the rise in sleep aid use and complaints of chronic insomniacs that it will be of great interest to identify new more effective / safe treatments as OTC sleep aids are not curative and tend to be habit forming. Suvorexant was recently approved as a prescription drug in August 2014 for the treatment of adults who have trouble falling asleep or staying asleep. This article attempts to present a review on therapeutic profile of this newly approved orexin receptor antagonist.

Abstract Online: 30-July-15

15. Analagesic Effect of Levetiracetam in Rat Models of Pain
Geeta Soren, Devarashetty Santoshi Roopa, Yashmiana Sridhar, Divyalasya TVSRama Mohan Pathapati, Madhavulu Buchineni
Background: Antiepileptic drugs are widely used to treat multiple non-epileptic disorders such as neuropathic and inflammatory pain, migraine, essential tremors and psychiatric disorders. Levetiracetam is a novel antiepileptic drug with a broad spectrum of anticonvulsant activity with high safety margin. We evaluated the analgesic effect of levetiracetam in inflammatory induced hyperalgesia in albino rats. Methods:  In this study male Wister rats weighing between 200-250 grams were taken and divided into 5 groups with 6 rats in each group. Levetiracetam was administered orally at a dose of 50mg/kg, 100 mg/kg, 200mg/kg and was compared with the control group which received distill water and the standard drug Aspirin at a dose of 100mg/kg. Hyperalgesia was induced by hot plate method. Reaction times were measured at 0, 30, 60 and 120 min after drug administration. Results: Levetiracetam at a dose of 100mg/kg after one hour of drug administration showed an increase in the reaction time compared to the saline. However, aspirin showed significant increase in the reaction time as compared to levetiracetam. Conclusion: Levetiracetam showed anti-hyperalgesia in animal model of pain and further study need to be conducted to evaluate the analgesic property.

Abstract Online: 31-July-15


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