Toxicity assessment of gelsenicine and the search for effective antidotes

Background Gelsenicine, one of the most toxic alkaloids of Gelsemium elegans Benth ( G. elegans), causes severe respiratory depression. However, its toxicity mechanisms are yet to be elucidated and no effective antidotes are available. Objective This study aimed to analyse the toxicity characteristics of gelsenicine. Methods Both acute and sub-acute toxicities were evaluated. Gelsenicine distribution and elimination in the central nervous system (CNS) and blood were observed. Effective antidotes for gelsenicine poisoning were screened. Results In the acute toxicity study, gelsenicine was highly toxic, and female rats exhibited greater sensitivity to gelsenicine than male rats (LD50 0.520 mg/kg vs 0.996 mg/kg, respectively). Death was primarily caused by respiratory failure. However, in the sub-acute toxicity study, no significant organ damage was observed. Gelsenicine was easily absorbed from the gastrointestinal tract and penetrated the blood–brain barrier, reaching peak concentrations in the CNS within 15 min and rapidly decreasing thereafter. Flumazenil or diazepam combined with epinephrine reversed gelsenicine toxicity and significantly improved survival rate in mice. Conclusions Gelsenicine is a highly toxic substance that affects nerve conduction without causing damage; the potential toxic mechanism is possibly associated with GABAA receptors. Our findings provide insights into the clinical treatment of gelsenicine -related poisoning and its toxicity mechanisms.

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Acute and subacute toxicity assessment of Madhulai Manappagu (Siddha herbal syrup formulation) in animal model

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2020-0327 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Meenakshi Sundaram Malayappan ◽

Gayathri Natarajan ◽

Logamanian Mockaiyathevar ◽

Meenakumari Ramasamy

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Oral Route ◽

Toxicity Assessment ◽

Toxicity Study ◽

Female Rats ◽

Albino Rats ◽

Oral Toxicity ◽

Gross Pathology ◽

Toxicity Studies

Abstract Objectives Madhulai Manappagu – a well-known sastric and widely prescribed Siddha herbal syrup formulation indicated for treating Veluppu Noi (Anaemia especially Iron deficiency Anaemia) has been in day today practice in Tamil Nadu for a quite longer decades. The syrup is a herbal preparation which has a sweet pleasant odour and a palatable taste, contain the juice of pomegranate (Punica granatum L.) as the main ingredient. Though the formulation is a fruit juice, the safety profile of the syrup is not established and is being marketed without toxicological evaluation. The study is aimed at ascertaining the acute and sub-acute toxicity assessment of Madhulai Manappagu in Wistar Albino rats. Methods The acute and sub-acute (28day repeated oral) toxicity studies were performed as per the guidelines mentioned in the Organization for Economic Cooperation and Development (OECD) 423 (adopted on December 2001) and TG 407 (adopted on October 2008) with slight modifications respectively. For acute toxicity study, three female rats were randomly selected as control; three female rats were randomly selected and were administered a single dose of 5,000 mg/kg body weight per oral route. For sub-acute (28day repeated oral) toxicity studies, three doses of test drug MM of 500 mg/kg/day (low dose), 750 mg/kg/day (intermittent dose) and 1,000 mg/kg/day (high dose) were selected for administration. Both sexes of Wistar Albino rats were randomized into four groups of 10 animals each (five males, five females). Group I was kept as control group. Group II, III and IV served as low, intermittent and high doses of MM respectively. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In the acute toxicity study, rats showed no toxicological signs on behavior, gross pathology and body weight of rats when treated with a single dose of 5,000 mg/kg body weight per oral route. In the subacute (28 days repeated oral) toxicity study, rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters when treated with Madhulai Manappagu in three different doses. Conclusions The toxicity studies which include both acute and 28 days repeated (subacute) oral toxicity studies, revealed no observed adverse effect level (NOAEL) of Madhulai Manappagu in animals. Thus the safety of the drug in human usage was ensured.

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Toxicity assessment of the methanol extract of Jatropha tanjorensis (Euphorbiaceae) leaves

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-021-00294-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

C. Christian Chibuogwu ◽

U. Obioma Njoku ◽

F. C. Okwesili Nwodo ◽

E. O. Vincent Ozougwu ◽

N. Victor Nweze

Keyword(s):

Acute Toxicity ◽

Biochemical Parameters ◽

Lethal Dose ◽

Toxicity Assessment ◽

Toxicity Study ◽

Acute Toxicity Study ◽

Relative Safety ◽

Liver And Kidney ◽

Potential Damage ◽

Dose Dependent Decrease

Abstract Background The leaves of Jatropha tanjorensis have been found to have important application both in traditional medicine and as an edible vegetable in Nigerian soups. It is popularly employed in Nigeria for the treatment of anemia, diabetes, and malaria. The dearth of information on its toxicity prompted this study. Mice were administered single oral doses of 10, 100, 1000, 1600, 2900, and 5000 mg/kg b.wt (n = 3/group) of the extract and were observed for 24 h for any sign of toxicity and mortality in the acute toxicity study. For the sub-acute toxicity study, doses of 100, 200, and 400 mg/kg b.wt of the extract were administered to experimental rats (n = 6/group) for 28 days after which the assessment of hematological and biochemical parameters, as well as liver and kidney histology was conducted post-treatment. Body weight of the animals was also taken weekly. Results The result showed that percentage weight gain decreased as the dose of extract increased. The haematological and biochemical parameters showed that the extract had no toxic effect on experimental animals, though there was a non-significant dose-dependent decrease in WBC. The extract also showed potential to cause hepatotoxicity at the highest dose. Conclusion Though the median lethal dose of the plant extract suggests relative safety of the plant material, consuming large amounts over a prolonged time may need to be discouraged to avoid potential damage to vital organs such as the liver.

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Acute and Subacute Toxic Aqueous Extract of the Leaves of Petroselinum Crispum Mill. in Male and Female Wistar Rats

European Scientific Journal ESJ ◽

10.19044/esj.2021.v17n40p178 ◽

2021 ◽

Vol 17 (40) ◽

pp. 178

Author(s):

Kablan Kassi Jean Jacques ◽

Blahi Adelaïde Nadia, ◽

Kouakou Koffi Roger ◽

Diby Yao Seraphin ◽

Siapo Yao Martin ◽

...

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Aqueous Extract ◽

Toxicity Study ◽

Female Rats ◽

Petroselinum Crispum ◽

Male And Female ◽

Acute Toxicity Study ◽

Male And Female Rats ◽

Female Wistar Rats

The present study is part of a vast program of the valorization of the medicinal flora and to help the populations to make a real profit from the use of plants in order to avoid any problem of poisoning. Petroselinum crispum Mill. (Apiaceae) is a plant, whose therapeutic virtues are diverse. The toxicological aspect of the aqueous extract of Petroselinum crispum leaves in male and female rats was investigated. The acute toxicity study with the single dose of 5000 mg/Kg body weight shows that the aqueous extract from the leaves of Petroselinum crispum is not toxic orally. According to Organisation for Economic Cooperation and Development (OECD) Guideline 423, the oral LD50 for this extract is greater than 5000 mg/kg body weight. In addition, the sub-acute toxicity study (OECD 407) showed that the aqueous extract from the leaves of Petroselinum crispum did not show any toxic effects at doses 50,100 and 200 mg/kg body weight and would have an orexigenic effect after 28 days of treatment. The different histological sections showed that the aqueous extract of Petroselinum crispum is not toxic on the vital organs and appears to be hepatoprotective.

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Effect of Methanolic Fruit Extract of Piper guineense on Serum Biochemical Parameters and Histomorphology of the Liver and Kidney of Male Albino Rats (Rattus norvegicus)

Notulae Scientia Biologicae ◽

10.15835/nsb919899 ◽

2017 ◽

Vol 9 (1) ◽

pp. 48-53 ◽

Cited By ~ 1

Author(s):

Chidozie N. OKOYE ◽

Izuchukwu S. OCHIOGU ◽

Onyinyechukwu A. AGINA ◽

Ukamaka U. EZE ◽

Nnenna O. NWACHUKWU ◽

...

Keyword(s):

Acute Toxicity ◽

Toxicity Study ◽

Male Rats ◽

Control Group ◽

Albino Rats ◽

Hepatocellular Injury ◽

Fruit Extract ◽

Biochemical Effect ◽

Piper Guineense ◽

Acute Toxicity Study

Piper guineense fruit is known for its nutritive and medicinal values. This study evaluated the biochemical effect of the methanol fruit extract of P. guineense on male albino rats. A total of thirty-eight (38) adult male Sprague-Dawley albino rats were used for the study. Eighteen of the male rats were used for the acute toxicity study, while twenty (20) male rats were randomly assigned into four groups (A, B, C and D) of 5 rats each, for the sub-acute toxicity study. Groups B, C and D were the treatment groups, while group A was the control group and received only distilled water (10 mg/ml). Groups B, C and D received 10 mg/kg, 200 mg/kg and 400 mg/kg body weight of the fruit extract respectively. Administration of the 100 mg/kg, 200 mg/kg and 400 mg/kg of methanol fruit extract of P. guineense led to a significant (P < 0.05) increase in the serum ALT and AP on day 7 of the experiment. Throughout the experimental period, 200 mg/kg of the extract caused a significant (P < 0.05) increase in serum total proteins and globulin. Group D rats had significantly (P < 0.05) lower serum total cholesterol on day 28 of the experiment. The 100 mg/kg of the extract caused a significant increase in serum urea and creatinine on day 21 of the experiment. Oral administration of methanol fruit extract of P. guineense caused mild hepatocellular injury, hyperproteinemia, hyperglobulinemia, hypocholesterolemia, and mild renal toxicity.

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TOXICOLOGICAL STUDY OF SURYASHEKHARA RASA

November 2020 - International Ayurvedic Medical Journal ◽

10.46607/iamj0708102020 ◽

2020 ◽

Vol 8 (10) ◽

pp. 4610-4616

Author(s):

Shanta Patil ◽

Surekha S Medikeri

Keyword(s):

Acute Toxicity ◽

Functional Group ◽

Research Work ◽

Toxic Substance ◽

Signs And Symptoms ◽

Toxicity Study ◽

Acute Administration ◽

Acute Toxicity Study ◽

Albino Mice ◽

Harmful Effects

Suryashekhara Rasa is unique mercurial preparation, which contains Parada, Gandhaka, Hingula and Vatsanabha. The quantity of Vatsanabha is equal to the sum of other ingredients, and also its antidote (Tankana) is not mentioned in this formulation. To ensure that the drug is devoid of toxicity and harmful effects, assessing the level of toxicity is important. So, this research work is an attempt to perform acute and sub-acute toxicity evaluation of Suryashekhara Rasa. Acute toxicity study of test drug was carried at a limit dose of 2000mg/kg orally in albino mice. For sub-acute toxicity Suryashekhara rasa was adminis-tered at therapeutic equivalent dose (TED) (0.35mg/kg bw po), TED x 2 (0.70mg/kg bw po) TED x 5 (1.75 mg/kg bw po) for 28 days. Acute toxicity result showed that drug did not produce any signs and symptoms of toxicity or mortality up to an oral dose of 2000 mg/kg in albino mice. The data generated during sub-acute toxicity study are indicated that it is mild toxic substance for sub-acute administration at TED dose level, may be because of alkanes which are found in functional group of aconitum ferox.

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PHARMACOGNOSTIC, ANTIOXIDANT AND ACUTE TOXICITY STUDY OF Ficus sycomorus (Linn) (Moraceae) ROOT AND STEM BARK

FUDMA Journal of Sciences ◽

10.33003/fjs-2020-0402-244 ◽

2020 ◽

Vol 4 (2) ◽

pp. 605-614

Author(s):

Murtala M. Namadina ◽

H. Haruna ◽

U. Sanusi

Keyword(s):

Acute Toxicity ◽

Radical Scavenging ◽

Stem Bark ◽

The Body ◽

Toxicity Study ◽

Bark Extract ◽

Root Extract ◽

Acute Toxicity Study ◽

Radical Scavenging Ability ◽

Phytochemical Components

Most of biochemical reactions in the body generates Reactive Oxygen Species (ROS), which are involved in the pathogenesis of oxidative stress-related disorders like diabetes, nephrotoxicity, cancer, cardiovascular disorders, inflammation and neurological disorders when they attack biochemical molecules like proteins, lipids and nucleic acid. Antioxidants are used to protect the cells or tissues against potential attack by ROS. Most medicinal plants possess a rich source of antioxidants such as flavonoids, phenols, tannins, alkaloids among others. These phytochemicals are currently pursued as an alternative and complimentary drug. In this study, phytochemical components, antioxidant and acute toxicity study of the methanol extract of stem bark and root of F. sycomorus were carried out using standard methods. Findings from this study revealed the presence of some diagnostic microscopical features such as calcium oxalate, starch, gum/mucilage, lignin, Aleurone grain, suberized/Cuticular cell wall and inulin but calcium carbonate was absent in stem bark but present in the powdered root. Quantitative physical constants include moisture contents (6.40% and 7.82%), ash value (7.20% and 9.30 %) in stem bark and root respectively. Carbohydrates, alkaloid, flavonoids, saponins, tannins, glycoside, steroid, triterpenes and phenols were present in all the extracts. They were found to exhibit potent 1,1,-diphenyl 2-picryl hydrazyl (DPPH) free scavenging activity. The DPPH radical scavenging ability of the extracts showed the following trend Ascorbic acid < stem bark extract˃ root extract. The LD50 of the methanolic stem bark and root extracts were found to be greater than 5000 mg /kg and is considered safe for use. Nonetheless, further

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In-vitro and in-vivo evaluation of antidiabetic activity of Withania coagulans extract

The Natural Products Journal ◽

10.2174/2210315509666190416155757 ◽

2019 ◽

Vol 09 ◽

Author(s):

Tejas Patel ◽

B.N. Suhagia

Keyword(s):

Blood Glucose ◽

Acute Toxicity ◽

Aqueous Extract ◽

Pancreatic Beta Cell ◽

Toxicity Study ◽

Acute Toxicity Study ◽

Withania Coagulans ◽

Study Results

Background: Diabetes mellitus is major issue to public health as its prevalence is rising day by day. Synthetic agents available for the diabetic treatment are expensive or produce undesirable side effect on chronic use and some of them are not suitable during pregnancy. Herbal medicines accepted widely due to side effects and low cost. Objective: The aim of present study was to evaluate the activity of Withania coagulans extract using In-vitro and In-vivo model. Methods: Different three types of Withania coagulans extract were prepared using aqueous (W1), Alcohol (W2) and hydro-alcoholic (50:50) mixture (W3). In-vitro Anti-diabetic activity of the all three extracts evaluated using RINm5F Pancreatic beta cells.Further, n-vivo anti-diabetic evaluation performed by administering 50 mg/kg (p.o) aqueous extract for 7 days in Streptozotocin (STZ)-induced mice. Body weight of the animals was also determined to perform acute toxicity study. Results: The results of in –vitro cell based study indicated that among all three extract, aqueous extract (W1) of Withania coagulans showed potential increase in inulin release. The EC50 of the W1 (249.6 µg/L) which is compared with standard (Glibenclamide) EC50. From the results of In-vitro study, W1 subjected for acute toxicity study and the acute toxicity study results indicated LD50 of 50mg/kg. Diabetic rats treated with W1 extract at oral dose of 50 mg/kg for 7 days showed 34.17% reduction in blood glucose in comparison to untreated diabetic (STZ-induced) rats. Blood glucose levels of Standard treated (Glibenclamide) and control untreated. Conclusion: In conclusion, results of pancreatic beta cell based study showed increase in insulin release by administration of extract. Further aqueous extract (W1) was potentially reduced blood glucose level in STZ induced diabetic mice.

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Safety Evaluation of Eucalyptus globulus Essential Oils through Acute and Sub-acute Toxicity and Skin Irritation in Mice and Rats

Current Chemical Biology ◽

10.2174/2212796814999200818095036 ◽

2020 ◽

Vol 14 (3) ◽

pp. 187-195

Author(s):

Berhan Mengiste ◽

Tizazu Zenebe ◽

Kassahun Dires ◽

Ermias Lulekal ◽

Awol Mekonnen ◽

...

Keyword(s):

Acute Toxicity ◽

Essential Oil ◽

Eucalyptus Globulus ◽

Biochemical Parameters ◽

Skin Irritation ◽

Toxicity Study ◽

Subacute Toxicity ◽

Acute Toxicity Study ◽

Limit Test ◽

Ointment Formulation

Background: The Eucalyptus globulus extractions have been used by the traditional healers to treat diseases in the study area. Our previous study revealed that the essential oil has antimicrobial and antifungal activity. This study determined phytochemical analysis, skin irritation, acute and subacute toxicity of Eucalyptus globulus essential oil in mice and rats. Methods: The phytochemicals were analyzed using GC-MS mass spectrometry. The acute toxicity study was determined at three dose levels of 1500 mg/kg, 1750mg/kg, and 2000 mg/kg. The essential oil limit test at a dose of 1000 mg/kg was administered to mice for 28 consecutive days for sub-acute toxicity study. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were analyzed for histopathological analyses. The 5% ointment formulation was applied to the rat skin to determine skin irritation effects. Results: The Eucalyptus globulus essential oil showed no effect on the mice at a dose of 1500mg/kg and below, but caused signs of toxicity and death at a dose of 1750mg/kg and above compared to the controls (p<0.05). The LD50 value was 1650 mg/kg. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control at 1000 mg/kg subacute toxicity study. No histopathological changes were detected in the organs tested. The 5% ointment formulation did not show any abnormal skin reaction. Discussion: In the present study, the Eucalyptus globulus essential oil was comparable with other studies in terms of both chemical composition and its effects on sub-acute and topical application. Conclusion: This toxicity study demonstrated that Eucalyptus globulus essential oil is nontoxic at a relatively lower concentration.

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