ABSTRACT
Background: The objective was to detect doxorubicin (Dox) - induced myocardial injury at early stage by quantitative estimation of cardio specific protein, cardiac troponin I (cTnI) and to explore the cardioprotective effects of carvedilol. Methods: The study design was lab-based randomized controlled in-vivo in rabbits conducted from January to August 2012. Cardiotoxicity was produced by single intravenous injection of 12 mg/kg body weight (BW) of Dox in a group of rabbits, control group was treated with normal saline only and the rabbits of third group were pre-treated with carvedilol 30 mg/kg of BW for 10 days before injecting Dox. Results: Dox induced cardiotoxicity was depicted by markedly raised serum levels of cTnI, creatine kinase-MB, lactate dehydrogenase, and Grade 3 necrosis of the heart tissue in rabbits. The pre-treatment with carvedilol resulted in improved serum levels of these biomarkers and the histological picture of heart tissue. Conclusions: Quantitative serum estimation of cTnI detects the presence of cardiotoxicity much before cardiac dysfunctions can be revealed by any other diagnostic technique. It can lead to significant economic impact in the management of cancer patients because the troponin-negative subjects can be excluded from long-term cardiac monitoring programs that involve high costs imaging techniques. The outcome of Dox chemotherapy can be made successful with the concurrent use of carvedilol.
ABSTRACT
To evaluate the acute effects of insulin on airway reactivity and the protective effects of beclomethasone and ipratropium against insulin-induced airway hyperresponsiveness on isolated tracheal smooth muscle in a guinea pig model. Materials and The trachea of each guinea pig was excised; one end of the tracheal strip was attached to the hook of the oxygen tube of a tissue bath and the other end was connected to a research-grade isometric force displacement transducer. The effects of varying concentrations of insulin [10[-7] to 10[-3]M] and insulin pretreated with a fixed concentration of beclomethasone [10[-6]M] and ipratropium [10[-6]M] on the isolated tracheal tissue were studied by constructing cumulative concentration-response curves. Changes in tracheal smooth muscle contractions were recorded on a 4-channel oscillograph. The means +/- standard error of the mean of the maximum amplitude of contraction with increasing concentrations of insulin and of insulin pretreated with fixed concentrations of beclomethasone and ipratropium were 35 +/- 1.13, 22 +/- 1.15 and 27.8 +/- 1.27 mm, respectively. The data showed that beclomethasone inhibited the contractile response of insulin to a greater extent than ipratropium. Thus we suggest that inhalational insulin pretreated with beclomethasone may be more efficacious than with ipratropium for the amelioration of potential respiratory adverse effects such as bronchoconstriction
ABSTRACT
Inhalational insulin was withdrawn from the market due to its potential to produce airway hyper-reactivity and bronchoconstriction. So the present study was designed to explore the acute effects of insulin on airway reactivity of guinea pigs and protective effects of salbutamol and beclomethasone against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. Effects of varying concentrations of insulin [10[-7] to 10[-3] M], insulin pretreated with fixed concentration of salbutamol [10[-7] M] and beclomethasone [10[-6] M] were studied on isolated tracheal tissue of guinea pig by constructing cumulative concentration response curves. Changes in tracheal smooth muscle contractions were recorded on four channel oscillograph. The mean +/- SEM of maximum amplitudes of contraction with increasing concentrations of insulin, insulin pretreated with fixed concentration of salbutamol and beclomethasone were 35 +/- 1.13 mm, 14.55 +/- 0.62 mm and 22 +/- 1.154 mm respectively. Although salbutamol and beclomethasone both had a profound inhibitory effect on insulin induced airway hyper-reactivity, yet salbutamol is more efficacious than beclomethasone. So we suggest that pretreatment of inhaled insulin with salbutamol may be preferred over beclomethasone in amelioration of its potential respiratory adverse effects such as bronchoconstriction
Subject(s)
Animals , Albuterol/pharmacology , Beclomethasone/pharmacology , Protective Agents , Insulin , Bronchial Hyperreactivity , Muscle, Smooth , Guinea PigsABSTRACT
To explore the inhibitory effects of montelukast against insulin induced tracheal smooth muscle contraction of guinea pigs in vitro. Inhalational insulin was withdrawn from market in 2007 due to its potential to produce airway hyper-reactivity and bronchoconstriction. So we investigated the acute effects of insulin on airway reactivity and protective effects of montelukast against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. Experimental study. This study was conducted in the Department of Pharmacology, Army Medical college Rawalpindi from December 2011 to June 2012. Effects of increasing concentrations of histamine [10[-8]- 10[-3] M], insulin [10[-8]- 10[-3] M] and insulin pretreated with fixed dose of montelukast [10[-5] M] were studied on isolated tracheal tissue of guinea pig. The tracheal smooth muscle contractions were recorded with Transducer on Four Channel Oscillograph.: Histamine and insulin produced a concentration dependent reversible contraction of isolated tracheal muscle of guinea pig. The mean +/- SEM of maximum amplitude of contraction with histamine was 92.5 +/- 1.20 mm as compared to 35 +/- 1.13 mm in insulin treated group. The maximum amplitude of contraction achieved with insulin in the presence of montelukast was 34.5 +/- 1.024 mm. Montelukast did not significantly inhibit the contractile response of insulin on isolated tracheal muscle of guinea pig, so pretreatment of inhaled insulin with montelukast has no clinical implication in amelioration of its respiratory adverse effects such as bronchoconstriction