The Irwin Test and Functional Observational Battery (FOB) for Assessing the Effects of Compounds on Behavior, Physiology, and Safety Pharmacology in Rodents

Mathiasen, Joanne R.; Moser, Virginia C.

doi:10.1002/cpph.43

Cited by 56 publications

(45 citation statements)

References 36 publications

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“…With no mortality observed at 5000 mg/kg, a confirmatory test was conducted to validate the observation. Using LD 50 as guide, and monitoring functional observational battery (FOB), 18 , 19 , 20 the sighting study 21 , 22 was conducted to determine the optimal doses for the acute and repeated dose toxicity studies, and humane endpoint criteria.…”

Section: Methodsmentioning

confidence: 99%

Biochemical, hematological and histopathological evaluation of the toxicity potential of the leaf extract of Stachytarpheta cayennensis in rats

Olayode

Daniyan

Olayiwola

2020

Journal of Traditional and Complementary Medicine

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Background and Aim The many pharmacological potentials of Stachytarpheta cayennensis (L.C. Rich) Vahl, especially in managing central nervous system disorders, hypertension, diabetes and infections, have made it a subject of abuse, necessitating the need to ascertain its safety. This study therefore investigated the toxic effects of the leaf extract of S. cayennensis in rats following acute and 28-day repeated doses in male and female rats. Experimental procedure Acute and repeated dose studies were conducted in male and female groups of rats (135–150 g), using OECD 423 and 407 Tests guidelines respectively. Functional observational battery, and body weights were monitored. Blood samples were analysed for haematological and plasma biochemical indices. Organs (brain, kidneys and liver) specimen were collected and weighed. Kidney and liver specimen were subjected to histopathological analysis. Results and conclusion The LD 50 of the extract was greater than 5000 mg/kg, p.o. (24 h) suggesting that the extract may be non-toxic. However, following single and repeated doses, the results revealed varying degree of significant (p < 0.05) changes in biochemical and heamatological indices, as well as in relative body weight and organ-body and organ-brain weight ratios. Also, histological assessment revealed evidence of liver and kidney toxicities and recovery was incomplete, as signs of toxicities were still evident after 21 days of recovery. Therefore, the extract is potentially harmful to vital organs with evidence of sex differential adverse effects and non-reversible forms of toxicity, especially with repeated usage, necessitating the need to avoid indiscriminate use.

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Section: Methodsmentioning

confidence: 99%

Biochemical, hematological and histopathological evaluation of the toxicity potential of the leaf extract of Stachytarpheta cayennensis in rats

Olayode

Daniyan

Olayiwola

2020

Journal of Traditional and Complementary Medicine

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“…The Irwin tests evaluate the main central and peripheral nervous system functions 23 and were used in the present studies for dose selection purposes. For this test, 24 male Sprague‐Dawley rats, approximately 9 weeks of age on the day of treatment, were used.…”

Section: Methodsmentioning

confidence: 99%

Effects of a selective long‐acting amylin receptor agonist on alcohol consumption, food intake and body weight in male and female rats

et al. 2020

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Alcohol use disorder is a complex neuropsychiatric disorder affecting both males and females worldwide; however, the efficacy of current pharmacotherapies varies. Recent advances show that gut‐brain peptides, like amylin, regulate alcohol behavioural responses by acting on brain areas involved in alcohol reward processes. Thus, the activation of amylin receptors (AMYRs) by salmon calcitonin (sCT) decreases alcohol behaviours in male rodents. Given that sCT also activates the sole calcitonin receptor (CTR), studies of more selective AMYR agonists in both male and female rodents are needed to explore amylinergic modulation of alcohol behaviours. Therefore, we investigated the effects of repeated administration of a selective long‐acting AMYR agonist, NNC0174‐1213 (AM1213), on alcohol, water and food intake, as well as body weight in male and female rats chronically exposed to alcohol. We confirm our previous studies with sCT in male rats, as repeated AM1213 administration for 2 weeks initially decreased alcohol intake in both male and female rats. However, this reduction ceases in both sexes on later sessions, accompanied by an increase in males. AM1213 reduced food intake and body weight in both male and female rats, with sustained body weight loss in males after discontinuation of the treatment. Moreover, AM1213 administration for 3 or 7 days, differentially altered dopamine, serotonin and their metabolites in the reward‐related areas in males and females, providing tentative, but different, downstream mechanism through which selective activation of AMYR may alter alcohol intake. Our data provide clarified insight into the importance of AMYRs for alcohol intake regulation in both sexes.

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“…The intervention was administered in dose-groups under anesthesia with ketamine and diazepam 75/5 mg/kg, intraperitoneal, single dose. Postadministration, the rats were monitored until recovery for 60-90 minutes on a thermic blanket and then monitored daily using a modi ed Irwin test 22 until euthanasia. The weight of all subjects was recorded at baseline, day 3 and at the day of euthanasia.…”

Section: Methodsmentioning

confidence: 99%

Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats

Chaccour

Abizanda

Irigoyen-Barrio

et al. 2020

Preprint

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Background: Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. Methods: An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals. Results: There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 grams/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs 26.2 ng/ml in the lower dose group and 152 ng/ml vs 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females. Conclusion: nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.

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The Irwin Test and Functional Observational Battery (FOB) for Assessing the Effects of Compounds on Behavior, Physiology, and Safety Pharmacology in Rodents

Cited by 56 publications

References 36 publications

Biochemical, hematological and histopathological evaluation of the toxicity potential of the leaf extract of Stachytarpheta cayennensis in rats

Biochemical, hematological and histopathological evaluation of the toxicity potential of the leaf extract of Stachytarpheta cayennensis in rats

Effects of a selective long‐acting amylin receptor agonist on alcohol consumption, food intake and body weight in male and female rats

Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats

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