The biochemical toxicology of some beta-adrenergic blocking agents.

A number of beta-adrenergic blocking agents were examined for their in vivo effects on the rat hepatic microsomal mixed-function oxygenase system to determine their potential for microsomal enzyme induction and epigenetic carcinogenesis. The method is based on previous findings that pretreatment of rats with chemical carcinogens preferentially stimulates biphenyl 2-hydroxylase and ethoxyresorufin O-deethylase, mixed-function oxidase activities catalysed by cytochrome P-448,the form of microsomal cytochrome known to be formed by chemical carcinogens. None of the beta-adrenergic blockers studied with the exception of propranolol and pronethalol, stimulated these cytochrome P-448-mediated enzyme activities at very high dosage. Mutagenicity studies of some of these beta-adrenergic blocking agents, using the Ames' bacterial and mammalian micronucleus tests, indicated that none of these agents give rise to significant and dose-dependent increases in mutations. The numbers of Hi[s+] revertant colonies produced with or without rat S-9 activation system and the number of micronucleated polychromatic cells formed in mice were not significantly increased over the spontaneous control levels. Because of a suggestion that practolol toxicity, namely, ulceration of intestinal, nasal and oral mucosae, and the conjunctiva of the eyes may involve inhibition of mucus synthesis, the efects of several beta-adrenergic blocking agents were studied. Only practolol significantly inhibited mucus glycoprotein synthesis as measured by the rates of incorporation of radiolabelled amino acid and sugar precursors into rat gastrointestinal mucus glycoproteins. None of the other agents studied showed any effects similar to practolol. It has further been suggested that some carcinogens, tumour-promoting agents and inhibitors of glycoprotein synthesis, preferentially stimulate tissue guanylate cyclase and cyclic GMP without concomitant increases in adenylate cyclase and cyclic AMP leading to a decrease in the ratios of adenylate/guanylate cyclases and C-AMP/C-GMP. None of the beta-adrenergic blocking drugs studied were shown to preferentially stimulate tissue guanylate cyclase and C-GMP. They did give rise to concomitant increases in tissue guanylate and adenylate cyclases and decreases in the C-AMP and C-GMP concentrations. However, there was no direct relationship between the ratios of adenylate/guanylate cyclases and C-AMP/C-GMP before and after treatment with the various agents

Absence of Organ Specific Toxicity in Rats Treated with Tonica, an Aqueous Herbal Haematinic Preparation

The sub-chronic toxicity of Tonica, an aqueous herbal haematinic prepared from the stem barks of Khaya senegalensis, Mitragyna stipulosa and Kigelia africana, was investigated in male Sprague-Dawley rats at 28, 280 and 560 mg kg−1 day−1, representing the normal human dose, 10x and 20x that dose, respectively for 6 weeks. The growth rate of animals over the period of treatment and certain serum biochemical and haematological indices as well as urinalysis and weight of selected organs at termination, were determined. Results show that the extract did not affect the weight gain of the animals with time or the mean wet weights of selected organs. Although there were slight but insignificant (p>0.05) elevations in WBC (16–27%) and PLT (8–11%) counts in Tonica-treated animals compared to controls at 10x and 20x the normal dose, most serum biochemical, haematological and urinalysis data indicated no significant differences (p>0.05) between tests and control rats. There were also no changes in the morphology of liver, kidney, lung and heart tissues as a result of Tonica treatment. These findings suggest that Tonica is safe at the dosage regimens administered to the animals in this study, and there appears to be no overt organ specific toxicity associated with it

Assesssing Herbal Medical Practitioners in Professional Qualifying Examination in Ghana, a Model

About 70% of Ghanaians depend on Alternative health practice for their primary health care needs. Hence, there is the need to streamline and regulate these practices. Graduates from the Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology (K.N.U.S.T), Kumasi-Ghana were assessed by the Professional Qualifying Examination Board of the Traditional Medicine Practice Council (TMPC), Ghana, after two years of internship training. A model of assessment took into consideration, the scope of the university training, internship and the primary health care needs of the society