In vivo protection studies of bis-quaternary 2-(hydroxyimino)-N-(pyridin-3-yl) acetamide derivatives (HNK oximes) against tabun and soman poisoning in Swiss albino mice

2017 ◽  
Vol 36 (12) ◽  
pp. 1270-1285 ◽  
Author(s):  
P Kumar ◽  
D Swami ◽  
DP Nagar ◽  
KP Singh ◽  
J Acharya ◽  
...  

The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum. Using various doses of tabun and soman (subcutaneously (sc)), in multiples of their IC50, AChE reactivation ability of the oximes was studied. Besides, acute toxicity (0.8× LD50, im, 24 h postexposure) of HNK-102 and 2-PAM was also compared by determining biochemical, hematological variables and making histopathological observations. Protection offered by HNK-102 against tabun poisoning was found to be four times higher compared to 2-PAM. However, nearly equal protection was noted with all the four oximes against soman poisoning. HNK-102 reactivated brain AChE activity by 1.5 times more than 2-PAM at IC50 dose of soman and tabun. Acute toxicity studies of HNK-102 and 2-PAM showed sporadic changes in urea, uric acid, aspartate aminotransferase, and so on compared to control group, however, not supported by histopathological investigations. The present investigation showed superiority of newly synthesized HNK-102 oxime over standard 2-PAM, as a better antidote, against acute poisoning of tabun (4.00 times) and soman (1.04 times), in Swiss albino mice.

2022 ◽  
Author(s):  
Joseph Tchamgoue ◽  
Amelework N. Eyado ◽  
Boniface P. Kamdem Kamdem ◽  
Yvan Anderson T. Ngandjui Ngandjui ◽  
Jean Claude Tchouankeu ◽  
...  

Malaria is regarded as one of the most lethal diseases. Resistance to artemisinin and its derivatives jeopardises effective malaria treatment. Finding novel antimalarial chemicals is critical given the existing treatment situation. This work aimed to examine the antiplasmodial capabilities of <i>Pseudarthria hookeri</i> fractions and flavonoids in vivo. The fractions and compounds antiplasmodial activity were evaluated on male Swiss albino mice infected with <i>Plasmodium berghei</i>, and on healthy female Swiss albino mice, the crude extract's acute toxicity was assessed. The EtOAc fraction had significant antiplasmodial activity (32.53 percent suppression at 500 mg/kg BW) and considerably prolonged the survival period of infected mice (9.8 days) compared to control mice (7.8 days). Parasitaemia was dramatically reduced (85.01, 59.41, and 70.39 percent), and the mean survival time extended (11.33, 10.00, and 9.33 days) with 15, 20 and 35 mg/kg of quercetin (<b>1</b>), 7-O-benzyl-6-prenylpinocembrin (<b>6</b>) and 6,8-diprenyleriodictyol (<b>11</b>) (isolates of the EtOAc fraction), respectively. BW loss and PCV reduction were also averted. Moreover, at 2500 mg/kg, the crude extract of <i>P. hookeri</i> showed no acute toxicity in mice. LC-MS analysis of the EtOAc fraction enabled the identification of nine flavonoids, with <b>8</b> and <b>11</b> being the main components. The present investigation confirmed <i>P. hookeri</i>'s antiplasmodial action, substantiating its ethnomedicinal application for malaria treatment.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Sibhatu Gebrehiwot ◽  
Mohammed Shumbahri ◽  
Amelework Eyado ◽  
Tilahun Yohannes

The objective of the present study was to investigate phytochemical components, antiplasmodial activity (in vivo) and evaluate the toxicity of two local medicinal plants, namely, Salvadora persica L. and Balanites rotundifolia (Van Tiegh.) used in Afar ethnomedicine for the treatment of malaria. In this study, phytochemical screening has been done using standard methods and the existence of antiplasmodial compounds was detected in these plant extracts. Four-day Peter’s test was used to determine parasite inhibition, PCV was determined by Wintrob’s method, and effects against loss of body weight and improvements on survival time were determined. LD50s of the crude extracts have been also done. Acute toxicity studies of the extracts were carried out in Swiss albino mice prior to antimalarial activity test. All extracts revealed no obvious acute toxicities on mice up to the highest (5000mg/kg) dose given. The crude extract was estimated to have oral median lethal dose higher than 5,000 mg/kg. With the 4-day suppressive test, both plant extracts demonstrated dose-dependent significant reduction in parasitemia level at all test doses compared to the negative control: in the extract of B. rotundifolia 500 mg/kg extract (60.59±3.25%), 350 mg/kg extract (48.1±1.4), and 200 mg/kg extract (41.33±1.1%) were found. And in case of S. Persica 500 mg/kg extract (50.6±4.01%), 350 mg/kg extract (35.85±0.89), and 200 mg/kg extract (27.69±1.14%) were found. The results of this study provide support for the traditional therapeutic value and the reported antimalarial activity.


2019 ◽  
Vol 7 (4) ◽  
pp. 64
Author(s):  
Ndeye Fatou Kane ◽  
Mutinda Cleophas Kyama ◽  
Joseph Kangethe Nganga ◽  
Ahmed Hassanali ◽  
Mouhamadou Diallo ◽  
...  

2019 ◽  
Vol 8 (2) ◽  
pp. 133-138
Author(s):  
Peace ME. Ubulom ◽  
Ette O. Ettebong ◽  
Edidiong J. Udofia ◽  
Rachel S Inyang Etuk

Introduction: Ricinus communis is used by the people of Niger-Delta region of Nigeria, for the treatment of various ailments, especially malaria. This study evaluated the antiplasmodial potentials of the aqueous seed extract of R. communis, using Plasmodium berghei berghei. Methods: Acute toxicity study was carried out to determine the median lethal dose (LD50) of the extract. Antiplasmodial effect of the extract was assessed in suppressive, repository/ prophylactic and curative models, using Swiss albino mice (15-29 g). Mice were infected intraperitoneally with 0.2 mL of parasitized blood. Extract doses administered were 54.77, 109.54 and 164.32 mg/kg/d of the seed extract and each dose had 6 replicates. Artesunate (5 mg/kg/d) and pyrimethamine (1.2 mg/kg/d) were used as standard drugs, while distilled water (10 mL/kg/d) served as control. Results: Acute toxicity study produced LD50 of 547.72 mg/kg. The extract demonstrated a dosedependent reduction in parasitaemia in all tests. At the end of 4-day test, suppressive effect of 20.80, 49.00, 75.00 and 88.40% were obtained for doses 54.77, 109.54 and 164.32 mg/kg/d of the seed extract and artesunate, respectively. In the repository test pyrimethamine was more potent (72.26%) than the seed extract (9.47%–51.42%). The extract also exhibited appreciable curative effect. The activity of the seed extract was significant when compared with the control (P < 0.05). Mice treated with the seed extract and drugs survived for longer duration than the control group. Conclusion: The aqueous seed extract of R. communis has antiplasmodial potential and its active principle should be elucidated and further investigated to help in the ongoing fight against malaria.


2019 ◽  
Vol 24 ◽  
pp. 2515690X1989195
Author(s):  
Jemal Abdela

Traditionally people used Dodonaea viscosa for the treatment of various ailments, including diarrhea. Therefore, this study was aimed to evaluate the antidiarrheal activity of the 80% methanolic leaf extract of D viscosa against castor oil-induced diarrhea in mice models. Different doses of 80% methanolic leaf extract of D viscosa (100, 200, and 400 mg/kg) were evaluated for their antidiarrheal activities using castor oil–induced diarrhea, gastrointestinal transit, and enteropooling models in Swiss albino mice. At all test doses, the plant extract showed significant ( P < .05) inhibition in the frequency of defecation of wet feces and total fecal output as compared to the control group. Similarly, at all dose ranges used the plant extract demonstrated significant ( P < .05) reduction in an intraluminal fluid accumulation as compared to the untreated group. Besides, at higher doses, the plant extract also indicated significant ( P < .05) antimotility activity in comparison with the control. In conclusion, these findings illustrated that the 80% methanolic leaf extract of D viscosa supported the traditional claim of antidiarrheal activity of the plant though further investigations are warranted.


2014 ◽  
Vol 33 (12) ◽  
pp. 1199-1208 ◽  
Author(s):  
S Saini ◽  
N Nair ◽  
MR Saini

Effects on postnatal development of Swiss albino mice exposed to nickel (Ni2+) ions as nickel chloride haxahydrate (NiCl2·6H2O) during the gestation periods were evaluated in this study. Administration of Ni to pregnant females by gavage (46.125, 92.25, and 184.5 mg Ni/kg body weight (b.w.)) at doses below median lethal dose during 0–5 (preimplantation period), 6–13 (organogenetic period), and 14–18 days (fetal period) postconception. The dams were allowed to deliver and raise their pups. Significant ( p < 0.05) decrease in litter size was observed after 184.5 mg Ni/kg b.w. during the three gestation periods particularly from preimplantation period as compared to organogenetic and fetal periods in comparison with the control group. Exposure to 184.5 mg Ni/kg b.w. during fetal period revealed higher mortality as compared to organogenetic period. Exposure to 184.5 mg Ni/kg b.w. increased the eye, limb, and tail anomalies during organogenetic period. Gestation index from preimplantation period was low at all the doses. Live birth index decreased during preimplantation and organogenetic periods after 184.5 mg Ni/kg b.w. The viability and weanling of pups decreased during all periods after 92.25 and 184.5 mg Ni/kg b.w. doses. A dose-dependent highly significant ( p < 0.01) decrease in the body weight of offspring from day 0 to 6 weeks of age at all the doses during different gestation periods were observed. Maximum body weight decrease was observed in offspring from organogenetic period. This study concludes that young ones are vulnerable during different gestational and lactation period which indicates that Ni ingested by mothers constitutes a great threat to the progeny.


1970 ◽  
Vol 23 (02) ◽  
pp. 386-404 ◽  
Author(s):  
G Müller-Berghaus ◽  
H. G Lasch

SummaryThe role of Hageman factor in triggering intravascular coagulation has been studied in rabbits injected intravenously with Liquoid. Besides changes of coagulation parameters characteristic of consumption coagulopathy (e.g. decrease in platelet counts, fibrinogen levels, factor V activity), a pronounced drop in Hageman factor activity was observed after injection of Liquoid. Likewise, the partial thromboplastin time became prolonged.The activation of Hageman factor in vivo could be prevented by intravenous infusion of lysozyme. Twenty min after starting the lysozyme infusion, the partial thromboplastin time became prolonged from a mean of 29 sec to 108 sec. Animals infused with lysozyme and injected with a lethal dose of Liquoid did not develop a consumption coagulopathy. In the same manner, none of 10 animals treated with lysozyme developed the generalized Shwartzman reaction, whereas in the control group 19 out of 20 animals showed fibrin thrombi in the glomerular capillaries.From the present study it may be concluded that the intravascular coagulation process after intravenous injection of Liquoid is triggered by Hageman factor activation.


Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 654
Author(s):  
Vellingiri Manon Mani ◽  
Arockiam Jeyasundar Parimala Gnana Soundari ◽  
Balamuralikrishnan Balasubramanian ◽  
Sungkwon Park ◽  
Utthapon Issara ◽  
...  

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen’s Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.


Author(s):  
Surekha D. Shetty ◽  
Laxminarayana Bairy K. ◽  
AM Prasad ◽  
Satheesha Nayak B. ◽  
Ashwini Aithal P.

Background: Hormones play a vital role in initiating and maintenance of male reproductive or testicular function which includes the production of androgens and spermatozoa. Testosterone is essential for the initiation and maintenance of spermatogenesis. FSH is responsible for the stimulation of spermatogenesis. Semen analysis and hormone evaluation are essential parameters in the diagnosis of infertility in males. Objective: The aim of the present study is to evaluate the effect of sorafenib on FSH and intratesticular testosterone levels in male Swiss albino mice. Materials and Methods: The animals were segregated into control, positive control, and treatment groups (n=6). Treatment group received 25, 50 and 100 mg/kg body weight of sorafenib orally for seven consecutive days at intervals of 24 hours between two administrations. Positive control group received 100 mg/kg body weight of imatinib. The animals were sacrificed at the end of 1st, 2nd, 4th, 5th, 7th and 10th week after the last exposure to sorafenib. Results: The intratesticular testosterone level was significantly (P<0.05) reduced in treated groups and severe effect was observed on week 4th and 5th weeks. FSH level was increased significantly (P<0.05) in sorafenib treated groups of mice. Conclusion: The administration of sorafenib does affect testosterone and FSH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with sorafenib for advanced renal cell carcinoma, hepatocellular carcinoma and differentiated thyroid carcinoma.


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