Faidherbia albida (Del.) A. Chev (mimosoidae) is widely used in African traditional medicine (ATM) for management of fever, diarrhoea and human trypanosomiasis. Acute and sub-acute toxicity profiles of ethanolic stem bark extract of F. albida were evaluated in wistar albino rats. The acute toxicity was studied using the method of Lorke (1983). In the sub-acute toxicity study, four groups of six rats per group were used. The control group (1) received 10 ml normal saline/kg body weight while groups 2, 3 and 4 received oral daily doses of 125, 250 and 500 mg extract/kg body weight respectively for 21 days. The effects of the extract on clinical signs, feed and water intake, body weight changes, haematology, plasma biochemical parameters, relative organ weight (ROW) were evaluated. The oral LD 50 of the extract was estimated to be greater than 5000 mg/ kg body weight. The extract produced slight increase in body weight of rats given 125 mg extract/kg body weight. However, dose-dependent highly significant (P < 0.01) decrease in body weight was observed at 250 and 500 mg/ kg-treated rats in weeks 2 and 3 of the study. Feed and water intake was not affected by the treatment. ROW for all organs was not affected by the treatment except significant (P < 0.05) increase in the testes of rats treated with 250 and 500 mg extract/kg body weight. Although the treatment elicited highly significant (P < 0.01) changes in the levels of the hepatic and some of the haematological parameters, they were within the normal reference range for rats. This study revealed that while the stem bark of the plant may be considered relatively safe when used sub-acutely, further investigation is needed to ascertain its effect on the male reproductive system as well as its effect on chronic administration.
Hepatic NADPH-cytochrome P450 oxidoreductase null (HRN™) mice exhibit normal hepatic and extrahepatic biotransformation enzyme activities when compared to wild-type (WT) mice, but express no functional hepatic cytochrome P450 activities. When incubated in vitro with [(14)C]-diclofenac, liver microsomes from WT mice exhibited extensive biotransformation to oxidative and glucuronide metabolites and covalent binding to proteins was also observed. In contrast, whereas glucuronide conjugates and a quinone-imine metabolite were formed when [(14)C]-diclofenac was incubated with HRN™ mouse liver, only small quantities of P450-derived oxidative metabolites were produced in these samples and covalent binding to proteins was not observed. Livers from vehicle-treated HRN™ mice exhibited enhanced lipid accumulation, bile duct proliferation, hepatocellular degeneration and necrosis and inflammatory cell infiltration, which were not present in livers from WT mice. Elevated liver-derived alanine aminotransferase, glutamate dehydrogenase and alkaline phosphatase activities were also observed in plasma from HRN™ mice. When treated orally with diclofenac for 7 days, at 30 mg/kg/day, the severities of the abnormal liver histopathology and plasma liver enzyme findings in HRN™ mice were reduced markedly. Oral diclofenac administration did not alter the liver histopathology or elevate plasma enzyme activities of WT mice. These findings indicate that HRN™ mice are valuable for exploration of the role played by hepatic P450s in drug biotransformation, but poorly suited to investigations of drug-induced liver toxicity. Nevertheless, studies in HRN™ mice could provide novel insights into the role played by inflammation in liver injury and may aid the evaluation of new strategies for its treatment.
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