| dc.description.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. | en_US |
