Effect of Sulfadoxine-Pyrimethamine and Artesunate on Gastric Acid Secretion and Parietal Cell Mass in Rats

Abstract

In this study, the effects of two antimalarial drugs, sulfadoxine-pyrimethamine and artesunate, on Gastric Acid secretion (GAS), Parietal Cell Mass (PCM) and Gastric Mucous Cell Population (GMP) were investigated in rats randomly assigned into three groups viz: control, Sulfadoxine-pyrimethamine (SP, 1.25/25 mg/kg), artesunate (AS, 2 mg/kg). Basal GAS as well as secretion in response to histamine and carbachol was measured by continuous perfusion of the stomach with normal saline (1ml/minute) under urethane anaesthesia (0.6 mg/100 g). 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. Further assessment of the roles of histaminergic and muscarinic receptors were done using ranitidine (H₂ antagonist) and atropine (M₃ antagonist) in the treated animals. PCM and GMP were determined in the stomach samples by histometry. The basal acid output was 0.70 + 0.01 mmol/10 mins. Normal saline and SP produced no statistically different peak output compared with the basal (p>0.05). AS produced a significant reduction with a value of 0.45 + 0.03 mmol/10 mins (p<0.05). Histamine and carbachol elicited 107% and 100% change of acid secretion when compared with the basal output with the value of 1.45 + 0.04 mmol/10 mins and 1.40 + 0.03 mmol/10 mins respectively (p<0.001). SP and AS attenuated histamine-induced acid secretory rate with the peak value of 0.95 + 0.01 mmol/10 mins and 0.80 + 0.02 mmol/10 mins respectively. Similarly, the carbachol-induced acid secretory response was attenuated by SP and AS to a peak of 0.90 + 0.02 mmol/10 mins and 0.90 + 0.03 mmol/10 mins (p<0.05). SP and AS decreased significantly the parietal cell numbers in the gastric mucosa (13.8+ 0.3 cells/μm versus 15.2+0.8 cells/μm control; p<0.05) and (13.4+0.5 cells/μm versus 15.2+0.8 cells/μm control; p<0.05). On the other hand, mucus cell population was significant increased by SP and AS (19+0.7 cells/μm versus 17.4+0.5 cells/μm control; p<0.05) and (22.2+0.8 cells/μm versus 17.4+0.5 cells/μm control; p<0.05) respectively. Sulfadoxine-pyrimethamine and artesunate inhibit gastric acid secretion. They inhibited histamine (H₂) and muscarinic (M₃) receptors, and reduced parietal cell mass.

Keywords: Sulfadoxine-pyrimethamine, Artesunate, Gastric acid secretion, Histamine, Parietal cell mass.