Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Sep 2010
Role of oxidative stress in reproductive toxicity induced by co-administration of chloramphenicol and multivitamin-haematinics complex in rats.
Concurrent administration of chloramphenicol (CAP) with multivitamin-haematinics complex (MHC) is a common practice to cushioning anticipated anaemic effect of CAP in most developing countries. This study investigated the mechanism involved in CAP-induced reproductive toxicity as well as the effects of its co-administration with MHC in male rats. CAP and MHC were administered orally at therapeutic doses of 28 mg/kg body-weight and 0.08 ml/kg body-weight, respectively, every 6 hr for 10 days. ⋯ Significant increase in testicular alkaline phosphatase activity, lipid peroxidation and sperm abnormalities were accompanied by reduction in epididymal sperm number, sperm motility and live-dead ratio in all treatment groups whereas aminotransferase activities were unaffected. Treatment-related degeneration of the testes was evident in all treated animals. In summary, while MHC-induced testicular toxicity via oxidative stress, CAP did not and their combination is implicated in reproductive dysfunction within the time course of our investigation.
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Basic Clin. Pharmacol. Toxicol. · Aug 2010
Randomized Controlled TrialCo-administration of dextromethorphan and morphine: reduction of post-operative pain and lack of influence on morphine metabolism.
We investigated co-analgesic effect of dextromethorphan in adolescent post-operative patients with idiopathic scoliosis. In a double-blind study, 60 patients with ASA physical status I-II were randomised into two groups. Group dextromethorphan (n = 30; age: 15.9 +/- 2.4 years) was given oral dextromethorphan 30 or 45 mg 1 hr before surgery and 8, 20 and 32 hr after operation. ⋯ Dextromethorphan did not influence morphine glucuronidation, in terms of promotion of formation of any morphine glucuronides. In conclusion, in young patients subjected to spine surgery, addition of dextromethorphan to morphine reduced pain only in early post-operative period. In such patients, co-analgesic action of dextromethorphan was not associated with significant changes in plasma levels of morphine metabolites.
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Basic Clin. Pharmacol. Toxicol. · May 2010
A synthetic analogue of 20-HETE, 5,14-HEDGE, reverses endotoxin-induced hypotension via increased 20-HETE levels associated with decreased iNOS protein expression and vasodilator prostanoid production in rats.
Nitric oxide (NO) produced by inducible NO synthase (iNOS) is responsible for endotoxin (ET)-induced hypotension and vascular hyporeactivity and plays a major contributory role in the multiorgan failure. Endotoxic shock is also associated with an increase in vasodilator prostanoids as well as a decrease in endothelial NO synthase (eNOS) and cytochrome P450 4A protein expression, and production of a vasoconstrictor arachidonic acid product, 20-hydroxyeicosatetraenoic acid (20-HETE). The aim of this study was to investigate the effects of a synthetic analogue of 20-HETE, N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine (5,14-HEDGE), on the ET-induced changes in eNOS, iNOS and heat shock protein 90 (hsp90) expression as well as 20-HETE and vasodilator prostanoid (6-keto-PGF(1alpha) and PGE(2)) production. ⋯ These effects of ET on the iNOS protein expression and 6-keto-PGF(1alpha), PGE(2) and 20-HETE levels were prevented by 5,14-HEDGE. Furthermore, a competitive antagonist of vasoconstrictor effects of 20-HETE, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid, prevented the effects of 5,14-HEDGE on the ET-induced changes in systemic and renal levels of these prostanoids and 20-HETE. These data are consistent with the view that an increase in systemic and renal 20-HETE levels associated with a decrease in iNOS protein expression and vasodilator prostanoid production contributes to the effect of 5,14-HEDGE to prevent the hypotension during rat endotoxemia.
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Basic Clin. Pharmacol. Toxicol. · Apr 2010
ReviewAmelioration of oxaliplatin neurotoxicity by drugs in humans and experimental animals: a minireview of recent literature.
The broad spectrum anti-neoplastic drug oxaliplatin is a third-generation platinum compound that inhibits DNA synthesis, mainly by causing intrastrandal cross-links in DNA. The drug is particularly useful alone and in combination with fluoruracil and leucovorin in colorectal cancer, but it is also used for other cancers such as those of the ovary, lung, breast and liver, as well as non-Hodgkin's lymphoma. The drug is known to cause neurological, gastrointestinal and haematological toxicities. ⋯ Strategies to ameliorate oxaliplatin neurotoxicity include the use of several 'neuroprotective' drugs. This MiniReview attempts to list and comment on the action and use of some of these agents, which include carbamazepine, gabapentin, calcium and magnesium salts, reduced glutathione, N-acetylcysteine and a few others. None of these drugs have been proven to be effective in large, controlled, clinical trials.
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Basic Clin. Pharmacol. Toxicol. · Aug 2009
Randomized Controlled TrialEvoked human oesophageal hyperalgesia: a potential tool for analgesic evaluation?
Hypersensitivity is a common finding in visceral disorders. Therefore, in the development and testing of analgesics for the treatment of visceral pain, it is important to establish an experimental pain model of visceral hypersensitivity. Such a model will mimic the clinical situation to a higher degree than pain models where the receptors and peripheral afferents are briefly activated as with, for example, electrical, thermal, and mechanical stimulations. ⋯ Acid+capsaicin perfusion induced 56% reduction of the pain threshold to heat (P = 0.04), 19% reduction of the pain threshold to electrical stimuli (P < 0.001), 78% increase of the referred pain areas to mechanical stimulation (P < 0.001) and 52% increase of the referred pain areas to electrical stimulus (P = 0.045). All volunteers were sensitised to one or more modalities by acid+capsaicin. The model was able to evoke consistent hyperalgesia and may be useful in future pharmacological studies.