Esophagus and Stomach

Uehara, Takeki; Elmore, Susan A.; Szabo, Kathleen A.

doi:10.1016/b978-0-12-391448-4.00006-x

Cited by 5 publications

(5 citation statements)

References 57 publications

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“…При оценке местно-раздражающего действия по результатам гистологического исследования на 91-й день эксперимента обнаружен один случай катарального гастрита в группе самцов крыс, получавших тестируемый препарат в дозе 90 мг/кг. Учитывая низкую частоту встречаемости (3,3% от общего числа животных) данного патологического изменения в условиях проведенного эксперимента, а также то, что подобные изменения в тканях желудка могут рассматриваться как фоновая патология, связанная со способом введения [25], можно сделать вывод о том, что препарат в исследованном диапазоне доз не оказал местно-раздражающего действия. У кроликов патологических изменений органов ЖКТ не выявлено.…”

Section: Discussionunclassified

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Experimental Study of Toxic Properties of Vmu-2012-05 Drug – Original Non-Nucleeside Inhibitor of Hiv-1 Reverse Transcriptase

Вавилова¹,

Shekunova²,

Джайн

et al. 2021

Farm. farmakol. (Pâtigorsk)

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Antiretroviral therapy is currently the main component of treatment for HIV patients. The development of new, more effective and safer drugs is an urgent task.The aim of the research is to study the toxic properties of the finished dosage form (FDF) VMU-2012-05, a non-nucleoside reverse transcriptase inhibitor (1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil) for the HIV-1 infection treatment in single and repeated enteral administrations.Materials and methods. The study of toxic properties in single administrations was carried out on outbred mice; the drug was administered at the limiting dose of 2000 mg/kg (by reference to the active substance). For 90 days, in repeated daily administrations, the toxic properties were studied in rats of both sexes at the doses of 0 mg/kg (placebo), 9 mg/kg (1 HTD), 45 mg/kg (5 HTD), 90 mg/kg (10 HTD). The toxic properties were also studied in rabbits of both sexes within a 28-day administration at the doses of 0 mg/kg, 4 mg/kg (1 HTD), 20 mg/kg (5 HTD), 40 mg/kg (10 HTD); the recovery period 30 days. Clinical observations and examinations, body weight registrations, physiological and clinical laboratory studies were carried out during the experiment. At the end of the administration period (50% of animals) and at the end of the recovery period, a pathological examination was performed.Results. The LD50 of the drug is more than 2000 mg/kg. In the repeated administrations, the no observed adverse effect level (NOAEL) has been established. For rats, it is 9 mg/kg (1 HTD), for rabbits – 4 mg/kg (1 HTD). According to the results of the experiments carried out on rabbits and rats, the main target organ of the drug toxic effect is the liver. According to the data obtained in the study on rats, a toxic effect on the organs of the male reproductive system has been manifested (hypoplasia of the spermatogenic epithelium). Under the conditions of the experiment, the test drug had no effect on the gastrointestinal tract.Conclusion. The results have manifested a favorable safety profile of the drug, not inferior to the ones of a similar pharmacological group used in clinical practice; it can be considered a promising drug candidate for the HIV-1 infection treatment.

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Section: Discussionunclassified

“…Product monograph including patient medication information Predurant® Rilpivirine as rilpivirine hydrochloride Tablets,25 mg Oral. Janssen Inc. Submission Control No: 223865.…”

mentioning

confidence: 99%

Experimental Study of Toxic Properties of Vmu-2012-05 Drug – Original Non-Nucleeside Inhibitor of Hiv-1 Reverse Transcriptase

Вавилова¹,

Shekunova²,

Джайн

et al. 2021

Farm. farmakol. (Pâtigorsk)

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“…The ratio of stomach volume to rat body weight cannot be compared with that of humans. The tissue of the proximal part of the stomach of the rat accords to the tissue of the esophagus, called the forestomach [ 13 ]. A compartment of the stomach of the rat consists of the esophagus and the stomach [ 13 ].…”

Section: Methodsmentioning

confidence: 99%

“…The tissue of the proximal part of the stomach of the rat accords to the tissue of the esophagus, called the forestomach [ 13 ]. A compartment of the stomach of the rat consists of the esophagus and the stomach [ 13 ]. Accordingly, the stomach volume of the rat relative to its body weight is much higher than that of humans.…”

Section: Methodsmentioning

confidence: 99%

Lower Rate of Water Absorption of an Oral Rehydration Solution with Partially Hydrolyzed Guar Gum in Conscious Rats

et al. 2022

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The purpose of the present study was to elucidate the rate of water absorption of an oral rehydration solution containing partially hydrolyzed guar gum (PHGG) in the small intestine, which is the main site of water absorption when water is drunk. Seven-week-old male SD rats were employed. We prepared four types of an aqueous solution, i.e., containing mineral and sugar, containing PHGG, containing mineral and sugar and PHGG, or containing no additives. After 24 h of food and 4 h of water deprivation, the aqueous solutions were infused into the stomach of conscious rats on their hands using a syringe with a stomach sonde. We sampled the stomach and the small intestine with contents 8 min after the infusions. Causal effects were calculated using a Bayesian network. PHGG increased the residual amount of water in the gastro-intestine, which depends negatively on the absorption of water in the small intestine/the flow rate to the small intestine. The absorption of water in the small intestine depended positively on the flow rate to the small intestine, which depended negatively on the free water in the solutions. PHGG decreased water absorption in the small intestine by decreasing the free water in the aqueous solutions.

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“…19 The forestomach is anatomically and functionally distinct from the glandular stomach and serves as an aglandular food reservoir which transfers food to the glandular stomach to meet energy demands. [20][21][22] Besides, macroscopic findings detected at necropsy were confined to enlarged, pale, and mottled kidneys and a dark liver in a number of males treated with 1000 mg/kg bw/ day, and enlarged kidneys for one male at 300 mg/kg bw/day. Microscopic examination also revealed effects in the kidneys of males from all Nonene treatment groups.…”

Section: Parental Toxicitymentioning

confidence: 98%

Toxicological Assessment of Higher Olefins in OECD TG 422 Repeated Dose and Reproductive /Developmental Toxicity Screening Tests in Han Wistar Rats

Shi,

Carrillo,

Penman

et al. 2023

Int J Toxicol

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Higher olefins (HO) are used primarily as intermediates in the production of other chemicals, such as polymers, fatty acids, plasticizer alcohols, surfactants, lubricants, amine oxides, and detergent alcohols. The potential toxicity of five HO (i.e., 1-Octene, Nonene, Decene, Hexadecene, and 1-Octadecene) with carbon ranging from C8 to C18 was examined in a combined repeated dose and reproduction/developmental toxicity screening study (OECD TG 422). These five HO were administered to Han Wistar rats by gavage at 0 (controls), 100, 300, and 1000 mg/kg bw/day. As a group of substances, adaptive changes in the liver (liver weight increase without pathological evidence), as well as increased kidney weight in male rats, were observed in HO with carbon numbers from C8 to C10. The overall systemic no observed adverse effect level (NOAEL) for all HO was determined at 1000 mg/kg bw/day. In the reproductive/developmental toxicity assessment, offspring viability, size, and weights were reduced in litters from females treated with Nonene at 1000 mg/kg bw/day. The overall no observed effects level (NOEL) for reproductive toxicity was considered to be 300 mg/kg bw/day for Nonene and 1000 mg/kg bw/day for the other four HO, respectively. These data significantly enrich the database on the toxicity of linear and branched HO, allowing comparison with similar data published on a range of linear and branched HO. Comparisons between structural class and study outcome provide further supportive data in order to validate the read-across hypothesis as part of an overall holistic testing strategy.

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Esophagus and Stomach

Cited by 5 publications

References 57 publications

Experimental Study of Toxic Properties of Vmu-2012-05 Drug – Original Non-Nucleeside Inhibitor of Hiv-1 Reverse Transcriptase

Experimental Study of Toxic Properties of Vmu-2012-05 Drug – Original Non-Nucleeside Inhibitor of Hiv-1 Reverse Transcriptase

Lower Rate of Water Absorption of an Oral Rehydration Solution with Partially Hydrolyzed Guar Gum in Conscious Rats

Toxicological Assessment of Higher Olefins in OECD TG 422 Repeated Dose and Reproductive /Developmental Toxicity Screening Tests in Han Wistar Rats

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