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Some studies on the rodenticidal action of indomethacin
E K Omogbai1, R I Ozolua, P E Idaewor
1Department of Pharmacology & Toxicology, University of Benin, Nigeria.
Abstract:
The oral LD50 of indomethacin for a seven-day observation was found to be 12.58 +/- 1.15 mg/kg. At LD10 of 6.61 mg/kg, a dose to weight ratio of 28 was obtained for a 240 g rat, while at a maximum single dose of 3 mg/kg in man it is only 0.04. Neither diazepam nor phenobarbital influenced death at the doses of both drugs used. However, cholestyramine 2 g/kg/day was found to protect by 50% from the LD100 of indomethacin. Gross pathological studies showed dose-dependent ulceration and perforation (P < 0.001, 12 vs 24 mg/kg) and such lesions occurred in starved rats, were low in bile duct-ligated compared to sham-operated rats (P < 0.001) and were also low in cholestyramine-treated rats. Indomethacin-induced lethality in rats was found to be dose-dependent.
Insights
Indomethacin toxicity in rats is dose-dependent, with an oral LD50 of 12.58 mg/kg. Cholestyramine significantly protected rats from lethal indomethacin doses, reducing mortality by 50%.
Area of Science:
- Pharmacology
- Toxicology
- Gastroenterology
Background:
- Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) known for its potential gastrointestinal toxicity.
- Understanding the dose-response relationship and protective factors is crucial for safe clinical use.
Purpose of the Study:
- To determine the oral lethal dose 50% (LD50) of indomethacin in rats.
- To investigate the protective effects of cholestyramine against indomethacin-induced lethality and gastrointestinal lesions.
- To explore the influence of diazepam and phenobarbital on indomethacin toxicity.
Main Methods:
- Oral administration of indomethacin to rats to establish LD50 and LD10 values.
- Administration of cholestyramine, diazepam, and phenobarbital in conjunction with indomethacin.
- Gross pathological examination of gastrointestinal tissues to assess ulceration and perforation.
- Comparison of lesion severity in starved, bile duct-ligated, sham-operated, and cholestyramine-treated rats.
Main Results:
- The oral LD50 of indomethacin was determined to be 12.58 +/- 1.15 mg/kg in rats.
- Cholestyramine (2 g/kg/day) provided 50% protection against the LD100 of indomethacin.
- Dose-dependent gastric ulceration and perforation were observed, exacerbated in starved rats and reduced in bile duct-ligated and cholestyramine-treated rats.
- Diazepam and phenobarbital did not influence indomethacin-induced mortality at the tested doses.
Conclusions:
- Indomethacin-induced lethality and gastrointestinal damage in rats are dose-dependent.
- Cholestyramine demonstrates significant protective effects against indomethacin toxicity, likely by binding the drug in the gastrointestinal tract.
- Further research into cholestyramine as an adjunct therapy for NSAID-induced gastrointestinal injury is warranted.