Abstract

ROLE OF METFORMIN AND L-ARGININE COMBINATION IN SICKLE CELL DISEASE PAINS: A PILOT LABORATORY AND CLINICAL STUDY, AND MINI-REVIEW

Dr. S. E. Oriaifo*, Dr. D. O. Oriaifo and Dr. R. A. Oriaifo

ABSTRACT

Sickle cell disease (SCD) is an inherited disorder of haemoglobin which is frequent in areas of high malaria transmission. Deoxygenation-induced hemoglobin polymerization in SCD is the stimulus for the excessive inflammatory-oxidative cascade-induced pathobiology, where hemolysis and vaso-occlusive episodes with ischaemia-reperfusion are the drivers. SCD is termed a natural model of acute and chronic pain, maintained by peripheral and central sensitization. Metformin and l-arginine through epigenetic mechanisms are disease-modifying agents in SCD. Via the synergistic induction of HbF, they may have additive role in attenuating polymerization and hemolysis, the root causes of SCD pathobiology. The neutrophil,asymmetric dimethyl arginine (ADMA), endothelin-I (ET-I) and uric acid, which are also antagonized by metformin and l-arginine, may be central players in the progression of SCD-induced pathology in which nitric oxide resistance stands out prominently. The shortcomings of the opioids and of hydroxyurea in the management of SCD may be the impetus for the investigation of other drugs for SCD management. In the present report, the benefit of combined metformin and l-arginine for SCD-induced acute and chronic (nociplastic) pains was investigated. Metformin and l-arginine combination was found to significantly and additively decrease glucose, uric acid, WBC count and pain scores in SCD patients (P <0.O5) who may display high glycemic variability. The combination was also significantly additive in attenuating epileptogenesis in mice models. The combination deserves attention as an enviable additional remedy for SCD which merits further trials.

Keywords: Metformin, L-arginine, Nitric Oxide, Sickle Cell Disease, Neutrophil Activation, Acute Pains, Chronic Pains, Glycemic variability.