Abstract

EFFECT OF MISOPROSTOL ON TYPE 2 DIABETES MELLITUS-ASSOCIATED POST-STROKE COGNITIVE DEFICIT AND PERIPHERAL ARTERIAL DISEASE

Dr. S. E. Oriaifo*, Dr. N. Oriaifo, Dr. E. O. Okogbenin, Dr. C. Iruolagbe

ABSTRACT

Given the morbidity and mortality associated with type 2 diabetes mellitus, agents that may attenuate its negative impact are needed. The synthetic prostaglandin EI analogue and agonist for the PGE2 EPI-EP4 receptors, misoprostol, has shown promise as an agent with a favourable profile on cardiovascular and neuropsychiatric diseases. It acts via the EP2/EP4 receptors to enhance mitochondrial integrity which oppose the roles of EP1/EP2/EP3 receptor signalling in inflammation and neurodegenerative diseases. Nevertheless, recent studies suggest that EP4 receptor signalling, activation of the mammalian target of rapamycin complex I (mTORCI) and inhibition of the intracellular nucleotide-binding and oligomerisation domain (NOD)-like receptor by misoprostol may dose-dependently upregulate tumor growth, upregulate proteoglycan degradation in articular cartilage and impact negatively on anti-bacterial defence in elderly patients. The prospective study examined the vasoprotective and neuroprotective effects of misoprostol in human patients with diabetes-associated peripheral arterial disease and ischaemic stroke. Clinical parameters such as the Ankle-Brachial Index (ABI) and the Mini-Mental Status Examination (MMSE) were used. Misoprostol after 5 weeks significantly (P < 0.05) attenuated the symptoms of ischaemic pain due to peripheral arterial disease in 15 patients with diabetes using the ABI in addition to laboratory evaluations and improved cognition in 8 patients with stroke more significantly than low-dose aspirin using the MMSE. In conclusion, short-term misoprostol shows vasoprotective and neuroprotective effects and may be a welcome addition to agents that may decrease morbidity in some aging-related disorders associated with type 2 diabetes mellitus.

Keywords: misoprostol, diabetes mellitus, peripheral arterial disease, cognition, EP2, EP4.