An investigation on the effects of a rhenium (V) compound with uracil-derived ligands on markers associated with hepatic, cardiovascular and renal complications in diet-induced prediabetic rats = Ucwaningo ngemiphumela yerhenium (V) compound ene-uracil ezifweni eziyamene nesibindi, inhliziyo kanye nezinso emagundaneni ayedla kodwa esengcupheni yesifo sikashukela.

Abstract

Prediabetes is a metabolic disorder that often precedes the onset of type 2 diabetes mellitus. This development of this asymptomatic condition is associated with chronic consumption of high calorie diets and sedentary lifestyles. Prediabetes results in decreased insulin sensitivity in the peripheral tissues resulting in elevated blood glucose levels that are not high enough for a diagnosis of type 2 diabetes. This moderate hyperglycaemia has been shown to lead to trigger complications such as non-alcoholic fatty liver disease, renal dysfunction and cardiovascular disease which are generally only diagnosed during type 2 diabetes. The current management strategy for prediabetes consists of a combination of pharmacological and lifestyle intervention. The pharmacological agents such as metformin while lifestyle intervention involves dietary modification to lower calorie diets. Studies show that prediabetic patients tend to be more dependent pharmacological intervention and struggle with changing diets thus lowering the efficacy of drugs such as metformin. This often leads to the eventual development of prediabetes. Therefore, there is a need for new pharmacological agents that can remain effective in both the presence and absence of dietary intervention. In our laboratory we have synthesised a novel rhenium (v) compound with uracil-derived ligands that has shown promising biological activities that include anti-hyperglycaemic effects in diet-induced prediabetic rats. This compound was shown to improve insulin sensitivity in peripheral tissues in prediabetic rats. To advance from this knowledge, this study sought to investigate the effects of the rhenium (V) compound with uracil-derived ligands on markers associated with hepatic, cardiovascular and renal complications in diet induced prediabetic rats model.

Iqoqa.

Isendlalelo: Iziguli ezisengcupheni yokungenwa yisifo sikashukela zibhekene nokuba sengcupheni yokungenwa yizifo ezinhlobonhlobo, okubalwa kuzo isifo sesibindi, isifo senhliziyo, kanye nokulimala kwezinso ngenxa yesifo sikashukela. Uma sesihlahliwe isifo, indlela ephakanyiswayo ibandakanya ukuxutshwa kokwelapha ngemithi kanye nokushintsha indlela yokuphila. Kodwa-ke, kunenkinga eqoshwe phansi yokwahluleka kweziguli ezihluphekayo ukugcina imithetho eyamene nendlela yokudla, bagxile kakhulu ekusebenziseni imithi, okuholela ekutheni imithi ingasebenzi kahle. Ngenxa yalokhu, kunesidingo semithi emisha ezokwazi ukwelapha ngempumelelo ngisho indlela yokudla ingashintshiwe. Lolu cwaningo luhlose ukuhlola umthelela werhenium (V) compound ene-uracil-derived ligands kwabaqokiwe asebecishe bangenwe ushukela, kubhekwa kokubili ukuba khona nokungabi khona kokungenelela ngokudla.

Izindlela zokuqhuba ucwaningo: Amagundane ajovwa ngeprediabetes ewuhlobo oluhlala amasonto angama-20 anomsoco wamafutha kanye nezinikamandla. Emuva kokujovwa, amagundane aqokwa ngokuwola afakwa ekulashweni ngemithi ehlukahlukene. Ajovwa ngerhenium (V) compound elinganiselwa ku-15 mg/kg kanye ngosuku, njalo ngosuku lwesithathu Isikhathi esingamasonto ayi-12, kunganakwa ukuthi uhlobo lokudla kunjani.

Imiphumela: Engxenyeni yokuqala (1), ukujovwa ngerhenium (V) compound kwadala ukulapheka kwesibindi, ukunonophala komzimba kanye nokwakheka kwamafutha. Okokugcina, lokhu kwelashwa kwavimbela ukonakala kwesibindi okwafakazelwa ukwehla kwama-enzyme biomarkers esibindi. Engxenyeni yesibili (2), ukusebenzisa irhenium (V) compound kwadala ukwehla kokhwantalala kanye namapro-inflammatory cytokines markers. Lokhu kwehla kwayamaniswa nokwehla kwamazinga amatriglycerides anesisindo samafutha esiphansi. Ngaphezu kwalokho, kwaba nokubuyela esimweni kokukhiqizwa kwamafutha anesisindo esiphezulu kulawo magundane afakwa irhenium (V) compound. Engxenyeni yesithathu (3), ukusebenza kwezinso kwabuyela esimweni, okwabonakala ngokwenyuka kweGRF nokwehla kweKIM 1, ipodocin ne-aldosterone. Irhenium (V) compound yathuthukisa ukusebenza kwezinso ngokuvimbela ukhwantalala oluyamene nokwehla kukashukela ezinsweni kukona kokubili ukuba khona nokungabi bikho kokushintsha indlela yokudla.

Isiphetho: Imiphumela yakhombisa ukuthi irhenium (V) compound yaphumelela ukuvikela isibindi nezinso, kanti yathuthukisa ukusebenza kwenhliziyo kulawo magundane ayejovwe ngeprediabetic enokudla. Yize kunjalo, lusadingeka ucwaningo oluzocacisa kabanzi ngokusebenza nokulethwa kwemiphumela yalo muthi.