HISTOLOGICAL AND BIOCHEMICAL EFFECTS OF ARTEETHERTM ON THE LIVER OF WISTAR RATS

ArteetherTM is among the recent drugs that are used to combat choroquine-resistant malarial parasites. This study examined the effects of arteetherTM on enzyme biomarkers of the liver, serum protein concentrations, and liver morphology. Twenty (20) adult albino Wistar rats weighing 200 – 250 g were randomly divided into four groups (A, B, C and D) of five animals each, and used in this study. Group A rats were given intramuscular (i. m.) arteetherTM (3 mg/kg b. w.) daily for 3 days. Group B rats received i. m. arteetherTM (6 mg/kg b. w.) daily for 3 days. Group C rats were given i. m. arteetherTM (3 mg/kg b. w.) daily for 3 days. The same dose was repeated at two-weekly intervals for 4 further weeks, while group D rats which received normal saline (0.9 % w/ v, 3 ml/kg b.w.), served as controls. At the end of the experiment, the body weights of the animals were determined and recorded. Serum levels of alanine transaminase (ALT), aspartate transaminase (ASP), alkaline phosphatase (ALP), total protein (TP) and albumin were assayed, and histological studies were performed. Results obtained show no significant difference (

Studies on the pharmacology of some antimalarial drugs

Pharmacological studies of the antimalarial drugs chloroquine, primaquine, quinine, progtianil and pyrimethamine have been made. These studies have shown that the compounds possess a wide spectrum of pharmacological actions in common on many tissues and organ-systems. In most cases, their effects were biphasic, consisting of an initial stimulation followed by a more permanent inhibitory phase. All five antimalarial compounds, at low concentrations, reduced the base-line tone (tension) of all smooth muscles studied, and augmented electrically-induced contractions of the chick oesophagus, vas deferens and central ear artery preparations. Higher concentrations of the drugs dose-dependently contracted gastrointestinal smooth muscles and inhibited the spontaneous, myogenic rhythmic contractions of intestinal muscles, uterine strips and portal veins in vitro in a dose-dependent manner. In the same dose range they inhibited the electrically-evoked contractions of the chick oesophagus, vas deferens and central ear artery preparations. The drugs relaxed tracheal chain preparations contracted with acetylcholine (in the presence of physostigmine), carbachol, histamine and 5-hydroxytryptamine. In vitro, all five compounds antagonised the actions of standard spasmogens in all preparations examined. This spasmolytic effect of the drugs has been shown to be non-specific in nature. All the five compounds, in very low dosos, augmented the action of acetylcholine on frog rectus abdominis and chick biventer-cervicis muscles. High concentrations of the drugs themselves caused dose-related sustained contractions of the muscles in vitro. In similar concentrations they inhibited, or abolished, the actions of acetylcholine, carbachol, nicotine and potassium chloride. In some cases, low concentrations of the compounds, especially quinine, chloroquine and primaquine, augmented electrically-induced twitches of the chick biventer and rat hemi-diaphragm muscles in vitro, and of the soleus and tibialis anterior muscles of the cat in vivo. High doses of the compounds, themselves inhibited the twitches in a dose-related manner, and augmented the effects of neuromuscular blocking agents on the preparations. The drugs also inhibited tho tetanic as well as the intra-arterially injected acetylcholine- induced contractions of the tibialis anterior muscle in vivo. All the five compounds possessed anticholinesterase activity. In isolated cardiac muscle, all the five drugs studied increased the refractory period and caused negative inotropic and chronotropic responses. However, low concentrations of the quinoline compounds (primaquine, chloroquine and quinine) induced slight but measurable transient positive inotropic and chronotropic affects in the heart. Intravenous injections of each of the five compounds into anaesthetized cats produced similar cardiovascular changes. Those changes consisted of dose-dependent reductions in systemic and pulmonary arterial pressures, left ventricular pressure, left ventricular dP/dt max; and heart rate. Other changes consisted of dose-related increases in right atrial and left ventricular, end-diastolic pressures, P-R interval and QRS complex duration. All the compounds inhibited or abolished the pressor effects of intravenous noradrenaline on the cardiovascular system.Pharmacological studies of the antimalarial drugs chloroquine, primaquine, quinine, progtianil and pyrimethamine have been made. These studies have shown that the compounds possess a wide spectrum of pharmacological actions in common on many tissues and organ-systems. In most cases, their effects were biphasic, consisting of an initial stimulation followed by a more permanent inhibitory phase. All five antimalarial compounds, at low concentrations, reduced the base-line tone (tension) of all smooth muscles studied, and augmented electrically-induced contractions of the chick oesophagus, vas deferens and central ear artery preparations. Higher concentrations of the drugs dose-dependently contracted gastrointestinal smooth muscles and inhibited the spontaneous, myogenic rhythmic contractions of intestinal muscles, uterine strips and portal veins in vitro in a dose-dependent manner. In the same dose range they inhibited the electrically-evoked contractions of the chick oesophagus, vas deferens and central ear artery preparations. The drugs relaxed tracheal chain preparations contracted with acetylcholine (in the presence of physostigmine), carbachol, histamine and 5-hydroxytryptamine. In vitro, all five compounds antagonised the actions of standard spasmogens in all preparations examined. This spasmolytic effect of the drugs has been shown to be non-specific in nature. All the five compounds, in very low dosos, augmented the action of acetylcholine on frog rectus abdominis and chick biventer-cervicis muscles. High concentrations of the drugs themselves caused dose-related sustained contractions of the muscles in vitro. In similar concentrations they inhibited, or abolished, the actions of acetylcholine, carbachol, nicotine and potassium chloride. In some cases, low concentrations of the compounds, especially quinine, chloroquine and primaquine, augmented electrically-induced twitches of the chick biventer and rat hemi-diaphragm muscles in vitro, and of the soleus and tibialis anterior muscles of the cat in vivo. High doses of the compounds, themselves inhibited the twitches in a dose-related manner, and augmented the effects of neuromuscular blocking agents on the preparations. The drugs also inhibited tho tetanic as well as the intra-arterially injected acetylcholine- induced contractions of the tibialis anterior muscle in vivo. All the five compounds possessed anticholinesterase activity. In isolated cardiac muscle, all the five drugs studied increased the refractory period and caused negative inotropic and chronotropic responses. However, low concentrations of the quinoline compounds (primaquine, chloroquine and quinine) induced slight but measurable transient positive inotropic and chronotropic affects in the heart. Intravenous injections of each of the five compounds into anaesthetized cats produced similar cardiovascular changes. Those changes consisted of dose-dependent reductions in systemic and pulmonary arterial pressures, left ventricular pressure, left ventricular dP/dt max; and heart rate. Other changes consisted of dose-related increases in right atrial and left ventricular, end-diastolic pressures, P-R interval and QRS complex duration. All the compounds inhibited or abolished the pressor effects of intravenous noradrenaline on the cardiovascular system

Comparative anti-inflammatory properties of Capsaicin and ethylacetate extract of Capsicum frutescens linn [Solanaceae] in rats

Background: The analgesic effect of capsaicin (the active ingredient in Capsicum frutescens Linn. [Solanaceae]) had been reported in several studies. Current research is being directed at producing analgesics, anti-inflammatory agents with better side effect profile. Objectives: To investigate if either the ethyl acetate extract of Capsicum frutescens Linn. [Solanaceae] (CFE) or capsaicin (Fluka Biotechnika-CPF) (in addition to the known analgesic properties) has any anti-inflammatory effect comparable to nonsteroidal anti-inflammatory analgesics (NSAIDS). Methods: The effects of ethyl acetate extract of Capsicum frutescens Linn. [Solanaceae] (CFE) and capsaicin (Fluka Biotechnika-CPF)was examined on rat hind paw. Inflammation was induced in the rat’s hind paw by subplantar injections of fresh egg albumin (0.5 ml/kg). Diclofenac (100 mg/kg) was used as the reference anti-inflammatory agent for comparison, while distilled water was used as the placebo. The leucocytes count, corticosterone and C - reactive protein (CRP) levels were measured as biomarkers of inflammation. Data obtained were pooled and analysed using repeated ANOVA, in a general linear model with the CPSS software. Results: Sub-plantar injections of fresh egg albumin (0.5 ml/kg) produced profound and time-related oedema in the rat hind paw of the ‘control’ rats. Diclofenac (DIC, 100 mg/kg, i.p.) and reference capsaicin (CPF, 2.5 mg/kg, i.p.) significantly inhibited paw swelling at (p<0.05–0.001) (CI 95%) compared to distilled water-treated ‘controls’.While the corticosterone levels were all very low in 7 rats treated with capsaicin, the leucocytes count was within normal range in 9 rats. However, in 16 specimens randomly assigned for CRP levels, there were very high CRP readings, up to a magnitude of 10 times the normal range. Conclusion: Capsaicin in both forms (CFE and CPF) produced anti-inflammatory effects that were comparable to diclofenac in the experimental rat model at p<0.05. It may be concluded that capsaicin has both analgesic and anti-inflammatory properties