EFFECTS OF CHLOROQUINE, AMODIAQUINE, SULFADOXINE-PYRIMETHAMINE AND ARTESUNATE ON GASTRIC ACID SECRETION IN RATS

Abstract

Gastric Acid Secretion (GAS) plays an important role in ulcerogenesis. Some antimalaria drugs have been shown to interfere with gastric mucosal integrity, thereby facilitating the development of gastric ulceration. However, the mechanisms underlying the actions of these drugs on gastric ulceration have not been well investigated. This study was aimed at investigating the effects of chloroquine, amodiaquine, sulfadoxinepyrimethamine and artesunate on GAS and Parietal Cell Mass (PCM) in the rat. One hundred and sixty male albino rats weighing 180-220 g were randomly assigned into five groups viz: Normal saline (1 mL/kg), chloroquine (CQ, 3 mg/kg), amodiaquine (AQ, 10 mg/kg), sulfadoxine-pyrimethamine (SP, 1.25/25 mg/kg) and artesunate (AS, 2 mg/kg). Gastric acid secretion was measured by continuous perfusion method under urethane anaesthesia (0.6 mg/100 g). Ten minute effluent samples (10.0 ± 0.1 mL each) were collected via a pyloric cannula and titrated against 0.01 M NaOH using phenolphthalein as indicator. Acidity was expressed in mmol/10 minutes of collection. After obtaining a steady basal output response to normal saline in all animals, the antimalaria drugs were administered intramuscularly and the peak responses to each drug obtained. The effects of the drugs on GAS induced by histamine and carbachol were separately determined. Further assessment of the roles of histaminergic and muscarinic receptors were done using ranitidine (H2 antagonist) and atropine (M antagonist) in the treated animals. PCM was determined in the stomach samples by histometry. Data were analyzed using descriptive statistics, ANOVA and Students’ t-test at p=0.05. The basal acid output was 0.70±0.01 mmol/10 mins. Chloroquine significantly increased basal acid output to a peak of 1.35±0.03 mmol/10 mins. The peak acid secretory response to amodiaquine was 1.40±0.03 mmol/10 mins (p<0.05). Normal saline and sulfadoxinepyrimethamine produced no significant changes in peak output compared with the basal. Artesunate caused a significant reduction in GAS with a peak response of 0.45±0.03 mmol/10 mins. Histamine and carbachol elicited 123% and 107% increases in GAS when compared with the basal output respectively. Chloroquine and amodiaquine potentiated the stimulatory effect of histamine (146% and 161% respectively) and carbachol (123% and 131% respectively). Ranitidine and atropine significantly blocked the response but not completely. Conversely, the stimulatory effect of histamine was significantly reduced by sulfadoxine-pyrimethamine (35%) and artesunate (14%). The stimulatory effect of carbachol was significantly blocked by sulfadoxine-pyrimethamine (28%) and artesunate (28%). The PCM in normal saline group was 15.2±0.8 cells/μm. Sulfadoxinepyrimethamine and artesunate significantly decreased PCM in the gastric mucosa (13.8±0.3 cells/μm and 13.4±0.5 cells/μm respectively). On the other hand, chloroquine and amodiaquine significantly increased PCM in the gastric mucosa (21±0.7 cells/μm and 24±0.7 cells/μm). Chloroquine and amodiaquine stimulated histamine receptors thereby enhancing gastric acid secretion by the parietal cells. Artesunate produced a dual effect of inhibiting histamine receptors and stimulating acetylcholine receptors in the gastric mucosa.