International Journal of

Toxicological and Pharmacological Research

e-ISSN: 0975 5160

p-ISSN: 2820-2651

Peer Review Journal

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1. Potent Anti-Inflammatory Effect of Root of Sidaguri (Sida rhombifolia L) on Rat Periapical Lesion Model
Maria Tanumihardja, Nurhayaty Natsir, Indrya K Mattulata, Lukman M
Sidaguri (S. rhombifolia L) is one of the most important species of medicinal part in Indonesia as anti-inflammation. To clarify this, we investigated the anti-inflammatory effect of the root of S. rhombifolia on rat periapical lesion model. The incisivus teeth were drilled to expose the dental pulp to the oral cavity and apical lesions were induced with LPS isolated from Porphyromonas gingivalis. Pour plate method was used to determine the bacterial CFU of gingival crevicular fluid (GCF) and C-reactive protein (CRP) serum was examined by enzyme-linked immunosorbent assay. The results showed that the root of S. rhombifolia could not reduce the total bacteria of GCF; however, it could reduce the level of CRP compared to negative control (p<0.05). In conclusion, S. rhombifolia has anti-inflammatory potency on rat periapical lesion.

2. Anatomical Distribution of Spontaneous Iron Pigment Overload in the Liver of Han Wistar and Sprague-Dawley Rats
R Chamanza, M Gregori, I Taylor, V Miragliotta, V Mowat
The authors performed a retrospective study to determine and describe the incidence of spontaneous pigment overload in the liver of control Han Wistar and Sprague-Dawley rats. Data was collected from 1170 control animals (550 Han-Wistar and 620 Sprague-Dawley) from control dose groups from long term regulatory studies (104-week carcinogenicity studies). Further 628 control animals (300 Han-Wistar and 328 Sprague-Dawley) from control dose groups from short term regulatory studies (13-week and 4 weeks studies) evaluated at the authors’ laboratory between 2009 and 2011. Livers from Han Wistar and Sprague-Dawley rats were re-evaluated using special stains to identify the nature of the pigments. In the periportal hepatocytes and in scattered sinusoidal Kupffer cells, the predominant pigment was identified as haemosiderin and a diagnosis of spontaneous iron overload was made. A comparison between the two strains revealed higher incidences of iron overload in Han Wistar rats than Sprague-Dawley rats. A significant sex difference was observed in both strains but was greater in Han Wistar rats. An age-related increase in the incidence and severity of pigment deposition was also apparent. Since there is little compiled data on spontaneous pigment overload in the liver the aim of this report was to summarize and discuss the incidence, distribution and factors affecting the occurrence of this background finding in control rats on toxicity studies.

3. Chemical Constituents of Coprinopsis lagopus
Consolacion Y Ragasa, Maria Carmen S Tan, Ma Ellenita G De Castro, Judy Perez, Chien-Chang Shen
Chemical investigation of the dichloromethane extract of the fruiting bodies of Coprinopsis lagopus led to the isolation of 3β-linoleyloxyergosta-7,22-diene (1), ergosterol peroxide (2), linoleic acid (3) and triacylglycerols (4).  The structure of 1 was elucidated by extensive 1D and 2D NMR spectroscopy.

4. Cytotoxic Potential of Humic Acid Synthesized Silver Nano Plates Against Dalton’s Lymphoma Ascites
Prashob Peter K J, Kala K J, Nair S M
This is a first report on the cytotoxic activity of humic acid synthesized silver nanoplates (HAgNpl) against Dalton’s lymphoma ascites (DLA). Humic acid, a supramolecule, has been shown to possess various biological activities. Humic acid used in the present study for the synthesis of silver nanoplates is isolated from mangrove sediments. Chemical composition of the humic acid was analysed using solid state C-13 NMR spectroscopy. Morphology of nanoplates were investigated using SEM. Trypan blue viability assay was performed on Dalton’s Lymphoma Ascites (DLA cell lines) to evaluate the cytotoxic potential of the HAgNpl. Humic acid synthesized silver nanoplates proved to be effective against these malignant cells. The HAgNpl showed a dose dependent activity against DLA cells. This result highlights the potential role of HAgNpl in developing safe medicines against malignant lymphoma.

5. Evaluation of Long Term or High Dose Toxicity of Sulfadimethoxine-Trimethoprim in Broilers
Mosleh N, Ashrafi M, Shomali T, Mobarraei N, Ahmadi N
Although potentiated sulfonamides as effective and broad-spectrum antimicrobials are frequently used in broiler farms, prescribing these agents may be associated with concerns about their toxicity especially regarding the fact that their toxic and therapeutic doses are usually close. This study evaluates toxicity of sulfadimethoxine-trimethoprim due to administration of higher doses or for longer period than what is recommended in broilers with regard to clinical signs, gross pathological examination, histopathological changes of liver and kidney as well as selected serum parameters. We found that sulfadimethoxine-trimethoprim use is relatively safe in broilers although high doses may be more damaging than long term use especially with regard to kidney function. The outcome of this study is useful in reducing the concerns related to severe toxic effects in chickens when unintentional over administration has been occurred but does not affect the need for use of recommended dosages as indicated in drug label.

6. Study of Bioactive Methanolic Extract of Camponotus fellah Using Gas Chromatography – Mass Spectrum
Jenan Mohammed Ubaid, Mohanad Jawad Kadhim, Imad Hadi Hameed
GC-MS analysis of Camponotus fellah revealed the existence of the  Cyclopentaneacetaldehyde ,2-formyl-3-methyl-α-methylene-, Cyclohexene, 1-methyl-5-(1-methylethenyl)-,(R)-, Bicyclo[5.1.0]octane, 8-methylene-,5-Methyl-6-phenyltetrahydro – 1,3-oxazine-2-thione, Decane, 1-Heptanol, 2-propyl, Octane, -4-methyl, Cyclopentanol, 2-(2-propynyloxy)-, trans-, Hydroxylamine, O-decyl, Trans-2-Ethyl-2-hexen-1-ol, Cyclopropene,1-methyl-3-(2-methylcyclopropyl)-, 10-methyl-endo-tricyclo[]decane, Undecen-1-yne, (Z, Exo-Norbornyl propionate, 5,8,10-Undecatrien-3-ol, 3-Methylene-bicyclo[3.2.1]oct-6-en-8-ol, Cyclohexane, 1,3-butadienylidene- , Cyclopropane. -1-methyl-1-ethenyl-2-(2-furyl)-, Pyrroline, 1,2-dimethyl, Cyclooctene-1-carboxaldehyde, Cyclopentanol,1-(1-methylene-2-propenyl)-, Eicosanoic acid, phenylmethyl ester, Octahydrochromen-2-one, Methyl 12-oxo-9-dodecenoate, 14-Methylpentadec-9-enoic acid methyl ester, 10-Octadecenoic acid, methyl ester, 9-Octadecenoic acid (Z)-, phenylmethyl ester, 14-Octadecenal, Butyl 9-tetradecenoate. Camponotus fellah produce many important secondary metabolites with high biological activities.

7. Peroxidative Index: A New Marker in Kidney Toxicity Induced by Mercury
Trilianty Lestarisa, Francisca Diana Alexandra, Helena Jelita, Eko Suhartono
Oxidative stress is an important molecular mechanism for kidney injury in mercury (Hg) poisoning. Usually, oxidative stress was measured by measuring the levels reactive oxygen species (ROS) and antioxidant enzymatic activity. In this present study, we proposed a new marker for oxidative stress in kidney toxicity induced by Hg. The new marker is the peroxidative index (PI). In this experiment, a kidney sample was taken from male rats (Rattus novergicus). Samples then homogenized and divided into five groups with; T1 served as control which contains kidney homogenate only; T2 which contains kidney homogenate+0.1 mg/l of mercury chloride (HgCl); T3 which contains kidney homogenate+1 mg/l of HgCl; T4 which contains kidney homogenate+10 mg/l of HgCl; and T5 which contains kidney homogenate+100 mg/l of HgCl. After treatment, kidney catalase (CAT) and peroxidases (Pox) activity, PI, hydrogen peroxide (H2O2) and PC level were estimated. The results revealed that Hg level is strong negatively correlated with both CAT and Pox activities, and strongly positively correlated with PI. Also, the results revealed that PI is strongly positively correlated with PI with the presence of Hg in different concentration of Hg in kidney cells. In conclusion, PI might be a useful marker for oxidative stress in kidney damage induced by  Hg. For our knowledge, the proposed mechanism according to our results is Hg inhibited antioxidant enzymatic activity and increase ROS in the kidney. Thus, induced oxidative stress which promotes a further reaction to damage protein and resulted in kidney damage.

8. Antimicrobial Actions of Antihypertensives
Patil T R, Patil S, Patil A, Patil S T
The increased incidence of hypertension and diabetes mellitus worldwide puts the human health under peril. Susceptibility of these patients for various infections endangers their life. Alarmingly increasing antibacterial resistance is a cause of major concern. By the year 2015 chances of people dying due to drug resistant bacterial infections will be more than that from cancer. Hence there is a need for the development of potent newer antimicrobials or to test and confirm the antibacterial properties of non-antibacterial drugs used to treat various conditions. Hypertension is one area where the antihypertensive drugs used to treat the condition have proved their potential activity against various infections. The antihypertensive drugs which were observed to have antimicrobial action are calcium channel blockers like verapamil, amlodipine, nifedipine and lacidipine, central sympatholytic drug alpha methyl dopa and beta blocker like propranolol. Verapamil which is an ion channel blocker has shown potential against mycobacterium tuberculosis when used along with approved anti tubercular drugs and helped in prevention of drug resistance. Similarly, alpha methyl dopa showed significant in vitro activity against atypical mycobacteria. Propranolol exhibited anti fungal and antitoxoplasmal activity. Verapamil helped to reverse chloroquine resitance developed by plasmodium falcifarum malaria parasite. This suggests that  properties of  these antihypertensive in treating various bacterial and nonbacterial infections should be studied extensively by many clinical studies to authenticate their use.

9. Neurofunctional Effects of Gestational Methylmercury (MeHg) Exposure in Rats
Dinesh N Gandhi, Dhrupadsing K Rajput
Developmental origin of Health and Disease (DOHAD) hypothesis suggests that early life influences appear as the roots for placing the offspring at a high risk of perinatal mortality. Methylmercury (MeHg) is ubiquitous and persistent environmental pollutant and food contaminant. It’s neurotoxic, especially for the developing nervous system. Contrasting studies on the toxic effects of methymercury (MeHg) during developmental stages of Wistar rats, lead us to investigate the neurofunctional effects caused by its gestational exposure, devoid of any overt sign of toxicity and / or gross malformation. The present neurofunctional/behavioral effects in the offspring on postnatal day (PND) (1-28) were investigated following maternal exposure to methylmercury (0.5, 1.0 and 1.5 by oral gavages from gestation day (GD) 15 to till parturition.  Slowness of surface righting reflex and pivoting was gender specific with significantly observed in male offspring only. The offspring’s motor ability was investigated using rota rod shows dose dependent significant reduction in latency to fall (sec.) or spent shorter time on rotating rod (10 RPM; cut-off time: 60s) in male offspring.  There were significant reductions in forelimb hanging time, significant increases in hindlimb foot splay in female offspring and reductions in forelimb hanging time with MeHg treatment groups was observed. Significantly increases in CNS activity and excitability by measuring numbers of rear in either sex with high dose MeHg treatment group. These results, combined with those of our earlier study, suggest that gestational exposure would enhance the MeHg-induced maternal and embryo/fetal toxicity, confirmed the high-teratogenic potential along with postnatal neurofunctional/behavioral measurements revealed gender and dose specific impairment of neurofunctional/behavioral performance in offspring of mothers suggest to pay increased attention to MeHg concerning its exogenous use during pregnancy.

10. Detection of Volatile Compounds Produced by Pseudomonas aeruginosa Isolated from UTI Patients by Gas Chromatography-Mass Spectrometry
Nadia Altaee, Mohanad Jawad Kadhim, Imad Hadi Hameed
Pseudomonas aeruginosa bacteremia has become an important cause of mortality and morbidity over the past few decades. Bioactives were analyzed using gas chromatography-mass spectroscopy (GC-MS) techniques, then the in vitro antibacterial and antifungal activity of the methanolic extract was evaluated. Twenty nine bioactive compounds were identified in the methanolic extract of Pseudomonas aeruginosa. GC-MS analysis of Pseudomonas aeruginosa revealed the existence of the Oxime-,methoxy-phenyl, Edulan II, Methyl-4-[nitromethyl] -4- piperidinol,  Acetamide, N-methyl-N- [4-[2-fluoromethyl-1 -pyrrolidyl-2-buty, Oxaspiro[4,4] nonane -4-one, 2-isopropyl, Octahydrochromen-2-one, 3,7-Diazabicyclo[3.3.1] nonane, 9,9-dimethyl, N-[3-[N-Aziridyl] propylidene] tetrahydrofurfurylamine, N-[3-t-Butylimino-1, 2-dimethylpropyl] aziridine, Benzenemethanol-aminopropoxy)-3-methyl, Borabicyclo[3.3.1] nonane, 9-methylthio, Butanamide, 3-propionylhydrazono-N-(2-ethylphenyl), Dithiocarbamate, S-methyl-, N- (2-methyl-3-oxobutyl)- , dl-Allo-cystathionine, Deoxyspergualin, dl-2,6-Diaminoheptanedioic acid, Glycyl-D-asparagine, Hydroxyphenazine, 2,5-Piperazinedione, 3,6-bis(2-methylpropyl)-, Cyclohexen-3-ol-1-one, 2-[11-tetradecenoyl]-, Ergotaman -3′,6′,18-trione, 9,10-dihydro-12′-hydroxy-2’methyl, 3′,8,8′-Trimethoxy-3-piperidyl -2,2′-binaphthalene-1,1′,4,4′-tetr, Z-10-Methyl-11-tetradecen -1-ol propionate, -Cyclohex-3-enyl -propionic acid, Benzyl methyl ketone, Urea, N,N’-bis (2-hydroxyethyl, Cystine, Butanamide, N-(5-methyl- 3-isoxazoly)-2-[ [4-methyl-5-(2-methyl-, Dasycarpidan-1-methanol, acetate ( ester). Punica granatum (Crude) was very highly active (6.71±0.25) mm. The results of anti-fungal activity produced by Pseudomonas aeruginosa showed that the volatile compounds were highly effective to suppress the growth of Aspergillus fumigatus (6.000±0.32). Pseudomonas aeruginosa produce many important secondary metabolites with high biological activities. Based on the significance of employing bioactive compounds in pharmacy to produce drugs for the treatment of many diseases, the purification of compounds produced by Pseudomonas aeruginosa can be useful.

11. Increase Hsp90 in Rats’ Lungs Exposed to Self-Cure Acrylic Methyl Methacrylate Monomer
Al-Hourani Zeid A, Bibars Abdel Rahim M, Alfwaress Firas S, Shboul Yasemin A, AlShyyab Awni
Introduction: Methyl Methacrylate (MMA) is a clear, highly volatile flammable- liquid monomer, with unpleasant strong fruity odor. It is an ester compound that results from the reaction between methanol and methacrylic acid. Aim: this study aims to investigate the expression of hsp90, a heat shock protein, in lung tissue of rats exposed to MMA, subsequent to the oral administration of MMA monomer in rats. Methods: 20 Sprague-Dawley rats were randomly selected and divided into two groups: control group, and experimental group. The experimental group was orally administered 120 mg/kg of MMA daily 5 times per week for four weeks. Changes in the expression of HSP90 in the lung tissue were investigated using Immunohistochemistry technique. Results: rat in the experimental group showed statistically significant (p < 0.001) increase, by approximately 15 folds, in the expression of HSP90 compared to that in the control group. Conclusion: exposure to MMA increased hsp90 expression in rat lungs, which may explain, at least in part, the inflammatory interactions that are associated with exposure to MMA.


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