International Journal of

Toxicological and Pharmacological Research

e-ISSN: 0975 5160

p-ISSN: 2820-2651

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1. In vivo Studies: Effects of Arnica montana Linn. Extract on Blood, Urine and Histo-Pathological Parameters of Albino Rabbits
Farah-Saeed, Mansoor Ahmad
Arnica montana Linn. (Asteraceae) is well known for curing mental, emotional, spiritual shocks and physical injuries. Our present research is carried out to investigate the toxicological effect on albino rabbits of low dose of Arnica montana when administered orally for a period of three months. Hematological, biochemical, histo-pathological studies and urine analysis were carried out to evaluate effects of low dose of extract when given for 90 days. In male test group, all the blood parameters were observed to be elevated while in female were found to be lowered except platelet count that was elevated. Creatinine and uric acid levels were found raised in female test group as compared to male test group. Cardiac enzymes were elevated in male test group and were lowered in female test group. Male test group revealed decreased lipid profile and liver enzymes parameters whereas, female test group exhibited raised lipid profile and liver enzymes levels, respectively. Urine volume and specific gravity were found lowered in both male and female test group. Blood cells were observed in urine of female test group. No significant toxic effects were observed with low dose treatment of Arnica montana on the stomach, kidney and liver tissues of male rabbits. Whereas, areas of myocytolysis in right ventricular wall and inter-ventricular septum was observed on the heart tissues. Our results justify the well-documented uses of Arnica montana.

2. Acute and Sub-Chronic Oral Toxicity Studies of an Aqueous Extract of Hallea stipulosa (Rubiaceae) in Wistar Rats
Poualeu Kamani S L, Wansi S L, Mzoyem N J, Miaffo D, Nkeng-Efouet A P, Kamanyi A
Hallea stipulosa (Rubiaceae) is a Cameroonian medicinal herb traditionally used for the treatment of various ailments including diabetes, hypertension, diarrhea, and gastric ulcer. To determine safety margin from the use of this plant, acute and sub-chronic toxicity studies of the stem bark aqueous extract of Hallea stipulosa (AHES) were performed in rats. In acute toxicity, single oral administration 2000 mg/kg or 5000 mg/kg of AEHS caused neither toxicological symptoms nor mortality and the LD50 was estimated > 5000 mg/kg. In the sub-chronic oral toxicity, no significant variation in body weight and food intake was observed in treated animals compared to the control group. Water consumption decreased at 100 and 200 mg/kg, suggesting inhibitory effects of the extract on hypothalamic osmoreceptors that regulate thirst. No significant change in blood glucose, hematological parameters, total and direct bilirubin was observed. A reduction in the relative kidney weight was observed at 200 mg/kg. A reduction of serum levels of ALT, AST and protein was observed at 50, 100 and 200 mg/kg. The decrease in protein levels could reflect kidney dysfunction which would have resulted in the decline in the relative kidney weight. Histological analysis revealed no abnormalities in the structure and morphology of the heart, pancreas and kidneys. However, vascular congestion was observed on the histology of the liver at 100 and 200 mg/kg. The results indicate a broad safety margin of AEHS; however, any repeated use at higher doses exposes to liver and kidney impairements.

3. Acute and Sub-Acute Toxicity of Sida veronicifolia Aqueous Extract in Female Wistar Rats
M D Yemele, P B Telefo, H S I Mapon, C Nangue, C S P Fodouop, N S Njina, J T Mbemya, L L Lienou, S R Tagne, C S Goka, F Ngoula, F Nguemo, P F Moundipa
Ethnopharmacological relevance: Sida veronicifolia Lamb (Malvaceae) is commonly used in traditional medicine of Cameroon for the treatment of pregnancy and childbirth discomfort; however, no toxicological studies have been reported on the plant.  Aim of the study: The present study was carried out to evaluate the acute and sub-acute toxicity of the aqueous extract of this plant has been evaluated in female rats. Materials and methods: In the acute toxicity test four female Wistar rats were treated with a single dose of the AESV (5000 mg/kg) administered by oral gavage and observed for 14 days in order to identify signs of toxicity or death. In subchronic toxicity study, rats were divided into 4 groups of 5 animals each. Animals of group 2 to 4 received, by daily gavage three doses 60, 240 and 960 mg/kg of the AESV for 28 days. Body weight and food consumption were measured every four days and at the end of treatment were analysed hematological, biochemical and histopathological parameters. Results: Evaluation of acute toxicity indicated no apparent clinical change in the animals; the LD50 is higher than 5000 mg/kg. In the sub-acute toxicity study, the AESV did not affect the general behavior. Moreover, no significant difference was observed on the body weights and blood, urinary and organs biochemical parameters. However, food consumption significantly decreased at the dose 960 mg/kg; vascular congestion of hepatic portal vein, few hepatic fibrosis at the doses 240 and 960 mg/kg and few renal necrosis at the dose 960 mg/kg were registered on liver and kidney sections. Also, a significant decrease of lymphocytes percentage associate to an increase of those of granulocytes was observed in all treated groups comparatively to control. Conclusion: The results of the present study showed evidence of the non-toxic effect of S. veronicifolia at 60 mg/kg, the dose commonly used in traditional treatments of pregnancy complaints. However, in sub-acute treatment, higher doses could provoke histopathological damages in the liver and kidneys which could in part reversible. Thus the extract should be used with caution.

4. Anxiolytic Activity of Ethanolic Extract of Seeds of Cuminum cyminum Linn in Albino Wistar Rats
Kaur Harpreet, Singh Rajmeet, Gupta Sumeet, Kaur Jaswinder, Kaur Jasvir
The plant Cuminum cyminum linn. was found to be used by different traditional systems and folklore for the treatment of various CNS disorders. The aim of the present study was to investigate the anxiolytic activity of ethanolic extract of Cuminumcyminum in adult albino Wistar rats. The animal behavior was evaluated by anxiolytic activity using standard procedures in experimental animal models. The results revealed that ethanolic extract showed promising results in terms of statistical manner when compared with the control group. In conclusion, this plant exhibits anxiolytic activity in testing animals.

5. Effect of Rutacea Plant Extract (ADD-X) on Inflammatory Biomarkers, Cardiac LDL, Troponin T and Histological Changes in Ovariectomized Rats Fed with Heated Palm Oil
Kumeshini Sukalingam, Kamsiah Jaarin, Qodriyah Haji Mohd Saad, Suhaila Mohamed, Faizah Othman
Palm oil is chief vegetable oil usually consumed worldwide. The consumption of repeatedly heated palm oil produces detrimental effect that attributes to the development of cardiovascular diseases. This study was aimed to determine the effects of ADD-X and repeatedly heated palm oil mixed with 2% cholesterol diet on cardiac, inflammatory biomarkers and histogical changes in ovarectmized rats. Based on the administration of food, animals were divided into 7 groups with 6 rats each. All groups of the animals were ovariectomized except sham after anesthetized. The study was conducted for 6 months. Group I- Sham control fed with Normal rat chow (Sham); Group II- fed with Normal rat chow [Ovx (n)]; Group III- fed with 2% cholesterol chow [Ovx (c)]; Group IV-  fed with 2% cholesterol chow mixed with five times heated palm oil (5HPO); Group V- fed with 2% cholesterol chow mixed with five times heated palm oil and ADD-X extract (5HPO-X); Group VI- fed with 2% cholesterol chow mixed with ten times heated palm oil (10HPO); Group VII fed with 2% cholesterol chow mixed with ten times heated palm oil and ADD-X extract (10HPO-X). The rats were sacrificed at the end of the study; blood was collected for cardiac and inflammatory biomarkers. The cardiac tissues of all groups were obtained for biochemical parameters and processed for histopathological examinations. Five times (5HPO) and ten times heated (10HPO) palm oil caused  a significant (p<0.05) increase in the level of cardiac lactate dehydrogenase (LDH), troponin (Trp), serum C-reactive protein (CRP), Tumour necrosis factor-α (TNF-α), free fatty acids and triglycerides with increase in cardiac weight compared to control. The changes in the biochemical parameters and cardiac weight were significantly (p<0.05) attenuated by ADD-X supplementation to the heated oil. The histological sections of the heart showed presence of cardiac necrosis in the 5HPO and 10HPO. These histological changes were reduced with ADD-X supplementation. The consumption of repeatedly heated palm oil increases LDL, troponin, CRP, TNFα, triglyceride, FFA, heart weight and cause cardiac necrosis in the post menopausal rat models.  Those changes were attenuated by ADDX supplementation.

6. Effects of Fluoxetine Administration on Plasma Lipids and Depressive-Like Behavior Induced by Lipid Peroxidation in Cerebral Cortex in Diabetic Rats
Rebai Redouane, Boudah Abdennacer
Usually, depression is more common in people with diabetes than the general population. The objective of this study was to explore the effects of fluoxetine on lipid peroxidation in the brain, also on plasma lipid levels in diabetic rats after intraperitoneal injection of streptozotocin (60mg/kg). Diabetic rats were treated with fluoxetine for three weeks. The evaluation of depressive-like behavior and locomotor activity was done by using of two behavioral tests, the open field (OFT) and forced swimming (FST). On the last day of the experiment, blood samples were taken to determine blood glucose and plasma lipids, as well as the determination of malondialdehyde (MDA) in the cerebral cortex. It has been noted that treatment of diabetic rats with fluoxetine, significantly increased locomotor activity and reduces the immobility time in (FST). In addition, the same treatment decreases the lipid peroxidation in the cerebral cortex and shows a regulatory effect on glucose and plasma triglycerides.

7. A Study to Evaluate the Safety of Rapid and Conventional Rituximab Infusion in a Tertiary Care Centre
Janardhanan M, Nayak V, Thomas J, Bairy K L
Antibody-based therapy, in particular rituximab, is a promising strategy in the treatment of Non-Hodgkin lymphoma. Rituximab chemotherapy combinations have revolutionised the treatment outcomes in NHL. A major barrier to effective treatment of rituximab is the lengthy infusion time. Hence, by reducing the chair time of one patient from the conventional 4-6 hours to rapid (90 minutes) infusion, more number of patients can be accommodated in outpatient facility. A total of 40 patients who received rapid infusion of rituximab over 90 minutes and 30 patients who received conventional infusion were evaluated for the safety parameter. It was observed that rapid infusion was well tolerated with no grade 3 or 4 reaction and there was no significant difference in the safety analysis between the rapid and conventional infusion. Therefore, it can be concluded that rapid infusion of rituximab can be opted as a safer alternative to conventional infusion and also improves patient satisfaction.

8. Proton Pump Inhibitors and Melanocytes
Patil T R, Patil S, Patil A, Patil S T
Melanocytic disorders comprise of vitiligo as well as melanoma both of which constitute the extreme ends of this spectrum. Also both of these have proven to be formidable challenges in terms of treatment. Hence a variety of drugs have undergone experimentation in this field and its benefits and side effects discussed. Proton pump inhibitors (PPI) are popular class of drugs used in gastroesophageal disorder management. These drugs have gained popularity due to their efficacy and minimal toxicity. This article is an attempt to elucidate the various mechanisms involving role of PPIs in the above mentioned melanocytic disorders.

9. Carbohydrate Metabolizing Enzymes Activity in Streptozotocin Induced Diabetic Rats Treated with Aqueous Extract of Erythrina variegata L. Bark
Devaki K, Hemmalakshmi S, Priyanga S
Alteration in carbohydrate metabolizing enzymes in diabetes and the antidiabetic potential of aqueous extract of Erythrina variegata L. bark in streptozotocin (STZ) induced diabetic in Wistar albino rats was investigated. Diabetes was induced in rats by single intraperitoneal injection of streptozotocin (45mg/kg body weight). Three days after STZ induction, the diabetes rats were treated with aqueous extract of Erythrina variegata L. bark orally at the dose of 400 mg/kg body weight daily for 30 days period. Glibenclamide (2mg/kg, orally) was used as standard drug. In addition, changes in body weight, hepatic glycogen content and carbohydrate metabolic enzymes were estimated by standard protocols. The results showed that the aqueous extract of E. variegata L. bark significantly increases the body weight, glycogen content and normalize the carbohydrate metabolizing enzymes. From this study, it can be concluded that E. variegata L. possesses considerable anti-diabetic property in streptozotocin induced diabetic rats.

10.Screening of Antidiabetic Activity and Toxicity Studies of Cephalandra indica Naud
Anupam Jamwal, Suresh Kumar
Cephalandra indica Naud. (Ivy gourd, family Cucurbitaceae) has a long tradition of use in the treatment of diabetes. Therefore, it was envisaged to screen antidiabetic activity of various extracts and fractions of C. indica, and to subject bioactive extract for acute and sub-acute toxicity studies. C. indica aerial parts were defatted by extracting with petroleum ether (60-80º C). The marc was then subjected to successive extraction using solvents in increasing order of polarity viz. chloroform, methanol and water. All extracts were screened for antidiabetic activity using STZ-NAD type -II diabetic model at the doses of 100, 200 or 400 mg/kg, p.o. for fifteen days, once daily. The bioactive extract was fractionated with ethyl acetate. The ethyl acetate fraction was also screened for antidiabetic activity at doses of 25 or 50 mg/kg, p.o. for 10 days, once daily.  The glucose level in rats was determined using glucometer. Acute and Sub-acute studies were performed on bioactive extract as per OECD guidelines. Methanol extract and its ethyl acetate fraction significantly reduced the glucose level in rats. Acute toxicity study did not reveal any change in behavioral, neurological and autonomic profile. In sub acute toxicity studies, the methanol extract did not affect hematological and biochemical parameters in rats.

11. Triterpenes from Pittosporum resiniferum Hemsl
Agnes B Alimboyoguen, Kathlia A Cruz-De Castro, Ian A Van Altena, Consolacion Y Ragasa
Chemical investigation of the dichloromethane extract of the leaves of Pittosporu resiniferum Hemsl. yielded a mixture of uvaol (1) and erythrodiol (2).  The structures of 1 and 2 were identified by comparison of their NMR data with literature data.

12. Resistance of Culex pipiens (Diptera: Culicidae) to Organophosphate Insecticides in Centeral Morocco
eL-akhal Fouad, Maniar Saâd, El Bachir Adlaoui, Chafiqa Faraj, Badoc Alai, El Ouali Lalami Abdelhakim
In this work, carried out for the first time in the center of Morocco, the activity of four insecticides was studied in 2010 on the larvae of the stages three and four of Culex pipiens, which are known to be the responsible of nuisance and/or transmission of some parasitic illnesses especially during spring and summer. Six concentrations were used: 0.00125, 0.0025, 0.005, 0.0125, 0.025, 0.0625 mg/l and the negative control (0 mg/l). The lethal concentrations (LC50 and LC90) were determined according to the WHO protocol. LC50 of the four insecticides (Malathion, Fenthion, Temephos and Fenitrothion) were respectively 0.0066, 0.0081, 0.0053, 0.0069 mg/l and they were respectively 0.0228, 0.0188, 0.0305, 0.0314 mg/l for LC90.The population of Culex pipiens studied presents an important resistance for Temephos and Fenitrothion of 13.26 and 12.07 respectively. However, a beginning of resistance for Malathion was observed with the rate of 0.456, and 0.343 for Fenthion. A regular survey of the sensitivity of the dominant population imposes itself in the density and the mechanisms of the possible resistance implied. The results of this study can be used as database for the management of mosquito resistance to insecticides at local and national level.

13. Beneficial Effects of Msm Treatment on the Development of Experimental Colitis Induced by Acetic Acid
Al laham Shaza, Mansour Ghaytha
Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract. A number of medical strategies are available. In the present study, the anti-inflammatory and antioxidant effects of Methylsulfonylmethane (MSM) in treatment the acetic acid (A) induced model for UC in rats were examined. Methods: The groups were divided into normal control (N), acetic acid (A) control, and MSM (400mg/kg). Rats received treatment for six consecutive days after induction of colitis by intra-rectal acetic acid (2ml 4% v/v) administration.  On day 7, the rats were sacrificed, colon was removed, and the macroscopic, biochemical, and histopathological evaluations were performed. Results: The colon weight/length ratio was decreased significantly (? < 0.05). The glutathione (GSH) concentration was increased significantly (? < 0.05). The macroscopic and histopathological parameters were decreased, but it didn’t reduce significantly in the MSM treated groups compered to group A. Contrariwise the parameters of group A. Conclusions. The anti-inflammatory and antioxidant effects of MSM in treating the UC are due to its potential to reduce the colon weight/length ratio, and increased GSH.

14. Biological Activity and Preclinical Study of Toхciсologyсal Action of the Essential Oil of Ziziphora Bungeana Juz. from Kazakhstan
Zhaparkulova Кarlygash, Karaybayeva Aigerim, Nussirbekova Ainur, Kurbanov Galymzhan, Seitaliyeva Aida, Ibragimova Lilya, Sakipova Zuriyadda, Satbayeva Elmira, Ross Samir
Data on study of biological activity preclinical study of toхciсologyсal action of the essential oil of Ziziphora bungeana Juz. Family of Lamiaceae are presented in this article. The raw materials for the researching were collected in summer 2014 at the territory of the Republic of Kazakhstan, at the foothills of the Dzungarian Alatau during the flowering period. Essential oil of plant by hydrodistillation was obtained, the yield is 0.5 %. The component composition of essential oil was studied using GC/MS Clarus-SQ 8 (PerkinElmer). Antimicrobial, antifungal, antileichmanial activities of essential oil were studied. Antibacterial and antifungal activity were identified using the strain of 5 human-pathogenic bacteria (Staphylococcus aureus, St. aureus (MRSa), Escherichia coli, Pseudomonas aeruginosa, Mycobacterium intracellulare) and 5 fungi (Candida albicans, C. glabrata, C. krusei, Aspergillus fumigates, Cryptococcus neoformans). Antileishmanial activity of the sample was tested for its ability to inhibit Leishmania donovani. The affinity of the total extracts and isolated compounds towards cannabinoid and opioid receptors were carried out according to the published method. The data indicate that the oil exhibit moderate levels of binding with Cannabinoid receptor and that more actively was inhibition of CB1 receptors. Results obtained from Radioligand Receptor Binding Assay, indicate that Kappa (26,3% inh.) and Mu (31,9 % inh.) types are the most sensitive receptors, with the higher percent inhibition. Visually, signs of sensitizing effect were not observed on the 10th day of the experiment in 15 minutes and 24 hours after a single subconjunctival administration of the essential oil on mucous membrane of palpebral conjunctiva and guinea pigs; a slight reddening of the tear duct, appeared immediately after injection, disappeared for 30 minutes. The mucous membrane of the eye was not swollen, usual-colored. Hemorrhages were not found; increased lacrimation was not observed. During the observation period the some signs of irritant action (redness, swelling, etc.) on the mucous membranes of the conjunctiva was not observed, which indicates the absence of irritating action. General condition of the animals was without aberration during the whole observation time.

15. Chemical Composition and Antimicrobial Activity of the Essential Oil of Cupressus Sempervirens L. Leaves in Syria
Mohamad Jawad Khubeiz, Ghaytha MansourBahira Zahraa
In the present research the essential oil contents and compositions of individual plant from Cupressus sempervirens L. (Cupressaceae), grown in Damascus / Syria have been investigated. The antimicrobial activity of the essential oil was also discovered. The air-dried leaves were hydro-distilled, and the essential oil analyzed by GC-MS. The essential oil from C. sempervirens L. sample was tested for antimicrobial activities using agar disc diffusion technique to determine the diameter of growth inhibition zones. The macro dilution broth susceptibility assay was utilized to determine minimum inhibitory concentrations (MIC), and minimum bactericide concentration (MBC). Fourteen components were identified in the essential oil of C. sempervirens L. The main constituents of essential oil leaves were alpha-pinene (36.50%), 3-carene (22.17%), Germacrene D (12.81%), Terpinolen (5.18%), alpha-tepinnyl acetate (4.76), limonene (3.55%) and beta-myrcene (3.16%). The results of the antimicrobial activity tests revealed that the essential oil has rather a strong antimicrobial activity, especially against Streptococcus pyogenes, Staphylococcus aureus and Vibrio parahaemolyticus, with diameter of inhibition zones ranging from (38.9 ±0.16) to (43.2 ± 0.15) mm, it showed a modest antibacterial effect for Micrococcus luteus, Klebsiella  pneumonia and Pseudomonas aeruginosa, with inhibition zones in the range (8.5± 0.13) to (10.2 ±0.13) mm. Minimum inhibitory concentration (MIC) revealed the lowest activity against Micrococcus luteus, Klebsiella pneumoniae and Pseudomonas aeruginosa (3.2mg/mL), while the highest activity was against Streptococcus  pyogenes, Vibrio parahaemolyticus (1.6 mg/mL) and Staphylococcus aureus (0.4 mg/mL). The Minimum bactericidal concentration (MBC) activity was from (1.6 mg/mL) to (4.6 mg/mL).

16. Quinoline (Cas: 91-22-5) Effect on Pubertal Development and Thyroid Function in the Intact Peripubertal Female Rats
Ujawane, D.G., Hadiya, K.C., Poshiya, M.P., Mistry, J.T., Bhise, D.W., Patel, M.V. Rajkapoor, B.
Quinoline potential effects on pubertal development and thyroid function were quantified in the peripubertal female Wistar rats. A total of 60 peripubertal rats were divided into 4 groups comprised of 15 rats/group. Vehicle control (corn oil – 0 mg/kg), positive control – 1-chloro-2-nitrobenzene (100 mg CNB/kg) and two groups of Quinoline (QNL – 100 and 150/200) mg/kg were administered, from postnatal day (PND) 22–42 at the dose volume of 2.5 mL/kg. All animals were sacrificed approximately 2 hours following the last dose on PND 42. No treatment related mortality was observed in control, CNB, and 100 mg/kg QNL. At 200 mg/kg QNL, two mortalities, and a significant reduction in body weight were observed hence dose was reduced to 150 mg/kg from PND 25. Weakness and lethargy were observed in 150/200 mg/kg QNL group. Body weight, body weight gain, and feed consumption of the 100 and 150 mg/kg QNL groups were significantly decreased, compared to the vehicle control group. Body weight, body weight gain, and feed consumption of the positive control group were comparable with the vehicle control group. Out of 15 rats/group – 13 (G1), 5 (G2), 11 (G3), and 4 (G4) rats had complete vaginal opening. Terminal body weight of the 150 mg/kg QNL groups was significantly decreased, as compared to the vehicle control group. Absolute liver weight of CNB and QNL treated groups were significantly increased compared to the vehicle control group. Absolute organ weights (pituitary, adrenals, thyroid and parathyroid) of QNL treated groups were comparable to the vehicle control group. Thyroid hormone levels (T4 and TSH) of QNL treated groups were comparable. Based on the result of study, QNL had not altered pubertal development and thyroid function in peripubertal rats.

17. Phytochemical and Biological Analysis of Tinospora cordifolia
Gagandeep Kaur , Pranav Kumar Prabhakar , Uma Ranjan Lal , Ashish Suttee
The aim of this work was to do phytochemical extraction and screening and also evaluation of their antibacterial and antioxidant properties for Tinospora cordifolia. The crude drug (Stem part) was successively extracted by Soxhlet assembly using various solvents. Preliminary phytochemical screening of different extracts was carried out using several colour and precipitate chemical reagents as per described methods. Gram +ve bacteria (Staphylococcus aureus) and Gram–ve bacteria (Escherichia coli) using the agar wells dilution method. Preliminary phytochemical screening of T. cordifolia showed showed the presence of carbohydrates, glycosides, flavonoids, phenols, tannins and amino acids in the crude drug. T. cordifolia stem extracts exhibited marked dose dependent antimicrobial activity in vitro against both gram positive and gram negative bacteria and can be used as a good therapeutic approach for infectious disease management and therapy. Methanolic extract was found to be more potent against both the group of bacteria. The T. cordifolia stem has shown different types of phytochemicals. Methanolic extract of T. cordifolia stem exhibited better antioxidant potential also. Further studies on isolation of phyto-constituents and both in vitro and in vivo evaluation of pharmacological activities of isolated bioactive constituents of the crude drug are recommended as future works.

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