THE CHRONIC ORAL TOXICITY OF CAFFEINE

1965 ◽  
Vol 43 (6) ◽  
pp. 995-1007 ◽  
Author(s):  
Eldon M. Boyd ◽  
Mortimer Dolman ◽  
Lois M. Knight ◽  
E. Patricia Sheppard
Keyword(s):  
Water Levels ◽  
Gastric Ulcers ◽  
Albino Rats ◽  
Oral Toxicity ◽  
Glucose Content ◽  
Toxic Reaction ◽  
Drinking Habits ◽  
Self Mutilation ◽  
Daily Dose ◽  
Colonic Temperature

The toxicity of caffeine administered daily by intragastric cannula to female albino rats was determined over 100 days, i.e., 1/10 of the animal's life-span. The maximal LD0(0.1L) or maximal daily dose producing no deaths over 100 days was 110 ± 2.5 mg/kg; the LD50(0.1L), 150 ± 3.1 mg/kg; and the minimal LD100(0.1L), 191 ± 5.7 mg/kg. Doses of the order of the LD0(0.1L) produced a mild cerebral hyperemia, occasional psychotic-like self mutilation, gastric ulcers, and inhibition of oogenesis; hypertrophy of the salivary glands, gastrointestinal tract, liver, heart, kidneys, and lungs; a stressor reaction in the adrenal and thymus glands; minor changes in organ water levels; an occasional death apparently from bronchopneumonia; but in general a normal appearance, and no change in growth rate, eating and drinking habits, or in the volume, pH, and protein and glucose content of the urine. Doses of the order of the LD50(0.1L) also produced a polydipsia and diuresis and an occasional dermatitis; some degree of toxic nephritis, hepatitis, myositis, thyroiditis, and loss of red pulp in the spleen. Doses of the order of the minimal LD100(0.1L) and higher produced an increasingly more toxic reaction, which was similar to that seen in the syndrome at the acute oral LD50 dose and that due to fortnight partial starvation. Abrupt withdrawal of caffeine was followed for 1 week by decreased locomotor activity, a slight decrease in colonic temperature, and proteinuria and glycosuria.

THE CHRONIC ORAL TOXICITY OF SODIUM CHLORIDE AT THE RANGE OF THE LD50(0.1L)

1966 ◽  
Vol 44 (1) ◽  
pp. 157-172 ◽  
Author(s):  
Eldon M. Boyd ◽  
Miriam M. Abel ◽  
Lois M. Knight
Keyword(s):  
Sodium Chloride ◽  
Chronic Toxicity ◽  
Young Male ◽  
Albino Rats ◽  
Oral Toxicity ◽  
Stomach Tube ◽  
Once Daily ◽  
Daily Dose ◽  
Slight Fever ◽  
Dose Dependent

The chronic toxicity of sodium chloride was studied in young male albino rats given 2.57–6.14 g/kg in water by stomach tube once daily for 100 days or until half the animals had died, whichever occurred first. The LD50(0.1 L) or daily dose which killed 50% of the animals after administration for 100 days, i.e. 1/10 the animal's normal lifespan (0.1 L), was 2.69 ± 0.12 g/kg. It is suggested that the LD50(0.1 L) expressed as a percentage of the acute LD50 would provide a useful index of chronic toxicity; this is termed the C/A LD50(0.1 L) index, C meaning chronic and A acute. The value of this index was 72 for sodium chloride, 62 for benzylpenicillin, and 13 for atropine. Rats which survived doses of the order of the LD50(0.1 L) had no change in food intake but lost some body weight as daily dose increased. They had a dose-dependent polydipsia and polyuria. In the initial month of drug administration the rats developed a slight fever, proteinuria, and alkalinuria, and in the terminal month a slight hypothermia and aciduria, all of which were statistically significant but not dose-dependent. When deaths occurred within the first week or two, they were similar clinically and pathologically to those seen in studies on the acute oral toxicity of sodium chloride. Other deaths followed a period of hypothermic cachexia and were due to bronchopneumonia, associated with hepatitis, nephritis, arteriolitis, and occasionally encephalopathy, and accompanied by degeneration of the thymus, adrenals, and testes. Animals which survived for 100 days had developed a hypertrophied gastrointestinal mucosa but most other organs had lost weight, and there was some arteriolitis, myocarditis, pulmonary edema, and nephritis.

scholarly journals ANTI-ULCER STUDY OF STANDARDIZED ETHANOL ROOT EXTRACT OF AGANOSMA DICHOTOMA AND ISOLATED URSOLIC ACID

2017 ◽  
Vol 9 (4) ◽  
pp. 172
Author(s):  
Deepali Pandey ◽  
Apurva Joshi ◽  
Siva Hemalatha
Keyword(s):  
Ursolic Acid ◽  
Gastric Volume ◽  
Gastric Ph ◽  
Toxicity Study ◽  
Gastric Ulcers ◽  
Albino Rats ◽  
Histopathological Study ◽  
Root Extract ◽  
Oral Toxicity ◽  
Proton Pump Inhibition

Objective: Aganosma dichotoma K. Schum (Apocynaceae) has been traditionally used as an Ayurvedic ulcer treatment and the study scientifically validates the antiulcer effect of A. dichotoma ethanol root extract (EAD).Methods: The studies included the isolation, quantification of ursolic acid through HPTLC. Acute and sub-acute toxicity study of EAD for 28 d and antiulcer effect of ursolic acid (50 mg/kg, p. o.), EAD (100, 200 and 400 mg/kg, p. o.) were also evaluated on both the physical (pyloric ligation, PL; cold restrain stress, CRS;) and chemical (absolute ethanol, aspirin, ASP;) induced ulcer in Charles Foster albino rats for 7 d. The various gastric-ulcer parameters, viz. gastric pH, volume, acid-pepsin output, DNA content, H+K+-ATPase activity, mucus content, microvascular permeability, antioxidant enzyme, and gastric histopathological study were performed.Results: The isolated ursolic acid was characterized by NMR and mass spectrometer and quantified through HPTLC in EAD (4.26% w/w). Acute oral toxicity study indicated that LD50 of extract was ≥ 5 g/kg. EAD at the dose of 200 and 400 mg/kg, p. o. reduced the ulcer score in both physical and chemical-induced ulcer models. In PL model EAD (400 mg/kg, p. o.) and ursolic acid (50 mg/kg, p. o.) showed antisecretory property by inhibiting aggressive factors [increase in gastric pH (35.02%, 26.73%), whereas decreased gastric volume (43.55%, 34.35%) and acid-pepsin output (75.23%, 68.81%), respectively]. EAD at 400 mg/kg p. o. showed significant effect on proton pump inhibition while ursolic acid didn’t showed any effect.Conclusion: The effects of EAD were accredited mainly to the offensive mechanism and justify its traditional usage in the treatment of gastric ulcers.

Evaluation of the Antiulcer Activity of Ethanolic Leave Extracts of Saraca indica against Ethanol, Pylorus Ligature and Indomethacin Induced Ulcer in Albino Rats

2020 ◽  
Vol 16 (8) ◽  
pp. 1191-1196
Author(s):  
Pritt Verma ◽  
Shravan K. Paswan ◽  
Vishal K. Vishwakarma ◽  
Priyanshi Saxena ◽  
Chandana V. Rao ◽  
...  
Keyword(s):  
Mucosal Injury ◽  
Gastric Volume ◽  
Gastric Ulcers ◽  
Albino Rats ◽  
Antiulcer Activity ◽  
Cellulose Solution ◽  
Total Acidity ◽  
Ulcer Index ◽  
Standard Drug ◽  
High Doses

Background: To evaluate the antiulcer activity of ethanolic leaves extract of Saraca indica against ethanol, pylorus ligature and indomethacin in albino rats. Materials and Methods: Ulcer was produced by ethanol, pylorus ligature and indomethacin in albino rats. Five groups (n=6) of rats were orally pre-treated with carboxymethyl cellulose solution, and ranitidine (80 mg/kg) respectively. In ethanol induced ulcer, the animals were treated with 200 and 400 mg/kg b.w. ethanolic leave extracts of Saraca indica in 0.3% CMC solution, 60 minutes before oral administration of absolute ethanol to produce gastric mucosal injury. In indomethacin induced ulcer, the drug was administered orally at the dose of 30 mg/kg b.w. After 7-9 hours of administration of indomethacin (30 mg/kg); the animals were sacrificed with high doses of anesthesia. In the pylorus ligature method, volume of free acidity, gastric secretion, pH and total acidity were estimated. In all three models, the ulcer index and % protection were estimated. Results: The anti ulcer activity of ethanolic leave extracts of Saraca indica in ethanol, indomethacin and pylorus ligature models is evident from the significant (P<0.001) reduction in ulcer index. In pylorus ligature model, significant (P<0.001) reduction in total acidity gastric volume and increase in pH were observed when compared with the standard drug. Conclusion: Ethanolic leave extracts of Saraca indica were found to be significantly protective against ethanol, indomethacin and pylorus ligature induced gastric ulcers in the experimental albino rats. The result obtained suggest that ethanolic leave extracts of Saraca indica possesses significant anti-ulcer activity.

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

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.

scholarly journals Ameliorative effect of Albizzia procera leaves extract against experimentally induced gastric ulcer models in Wistar albino rats

2021 ◽  
Vol 13 (1) ◽  
pp. 308-315
Author(s):  
Vivek Srivastava ◽  
Santosh Kumar Verma ◽  
Neha Mathur ◽  
Kapil Kumar Goel
Keyword(s):  
Gastric Ulcer ◽  
Ethanolic Extract ◽  
Gastric Fluid ◽  
Gastric Ulcers ◽  
Albino Rats ◽  
Traditional Medicines ◽  
Pylorus Ligation ◽  
Ameliorative Effect ◽  
Wistar Albino Rats ◽  
Experimentally Induced

Albizzia procera belongs to family Fabaceae and has several phytoconstituents like flavonoids, terpenes, alkaloids, saponins etc. The plant is commonly used in traditional medicines. The objective of the present study was to assess the ameliorative effect of A. procera leaves extract against an experimentally induced gastric ulcer in albino rats. The antiulcer, antisecretory and cytoprotective properties of an ethanolic extract prepared from the leaves was evaluated. When given in a 200 mg/kg oral (per. os) dose, the extract produced 74% and 85% protection index in ethanol-induced ulcer model and pylorus ligation model, respectively.  Additionally, the extract also prohibited the formation of haemorrhage and edema, significantly lessened catalase activity (p<0.0001) and the lipid peroxidation level (p<0.0001) in the glandular tissue of Wistar albino rats. Furthermore, the extract also significantly diminished the total acidity(p<0.0001) of the gastric fluid by increasing its pH (p<0.0001). The occupancy of different phytoconstituents in the extract, such as flavonoids and tannins were identified that may be responsible for its gastro-protective activity. All these results provide a basis explaining the antiulcer ability of A. procera being useful in the management of gastric ulcers.

LIPID AND WATER LEVELS IN THE KIDNEYS OF ALBINO RATS BEARING WALKER CARCINOMA 256

1956 ◽  
Vol 34 (1) ◽  
pp. 259-264 ◽  
Author(s):  
Eldon M. Boyd ◽  
Arne O. Tikkala
Keyword(s):  
Fatty Acids ◽  
Total Cholesterol ◽  
Total Lipid ◽  
Free Cholesterol ◽  
Dry Weight ◽  
Water Levels ◽  
Albino Rats ◽  
Total Fatty Acids ◽  
Wet Weight ◽  
Walker Carcinoma

The kidneys of 54 pairs of twin albino rats, one inoculated and one not inoculated with Walker carcinoma 256, were analyzed for water, total lipid, neutral fat, total fatty acids, total cholesterol, ester cholesterol, free cholesterol, and phospholipid, calculated as gm. per 100 gm. nonlipid dry weight. Compared with the kidneys of their nontumor-bearing littermates, the kidneys of tumor-bearing rats exhibited no significant change in wet weight and in concentration of total lipid, neutral fat, total fatty acids, and ester cholesterol. There was a significant increase in concentration of water, total cholesterol, free cholesterol, and phospholipid. The increase was toward concentrations of corresponding elements in Walker carcinoma 256. The changes became evident in animals bearing tumors weighing 20 to 40% or more of host weight.

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