Cardioprotective effects of diallyl trisulfide on ischemic-reperfusion injury of isolated rat heart with metabolic syndrome: the role of oxidative stress

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Cilj: Cilj ovog istraživanja bio je da se ispitaju efekti hronične primene dialil trisulfida (DATS), najsnažnijeg i najvažnijeg prirodnog donora vodonik sulfida izolovanog iz belog luka, kod zdravih, pacova sa dijabetes melitusom (DM) i pacova sa metaboličkim sindromom (MetS). Posebna pažnja bila je usmerena ka ispitivanju kardioprotektivne uloge DATS-a, u ex vivo indukovanoj ishemijsko-reperfuzionoj (I/R) povredi miokarda, ali i njegovoj sposobnosti da umanji manifestacije dijabetesa i metaboličkog sindroma. Metode: U ovu eksperimentalnu, hroničnu studiju bilo je uključeno 72 pacova Wistar albino soja koji su bili razvrstani u 6 osnovnih grupa: zdravi pacovi netretirani i tretirani DATS-om (KTR i DATS), DM pacovi netretirani i tretirani DATS-om (DM i DM+DATS) i MetS pacovi netretirani i tretirani DATS-om (MS i MS+DATS). Tretman DATS-om podrazumevao je tronedeljnu per os primenu DATS-a svakog drugog dana u dozi od 40 mg/kg. Nakon hroničnog tretmana, životinje su žrtvovane pri čemu se svaka od osnovnih grupa razvrstavala na dve podgrupe u zavisnosti od protokola na Langendorff-ovom aparatu (90 minuta retrogradna perfuzija ili I/R povreda miokarda). Rezultati: DATS, primenjen kod navedenih grupa pacova, pokazao je značajne kardioprotektivne efekte, poboljšao je oporavak miokarda i doprineo očuvanju njegove funkcije nakon I/R povrede. Takođe, kod pacova sa DM značajno je umanjio nivoe glukoze, dok je kod pacova sa MetS-om ublažio manifestacije ove bolesti (koji se ogledaju kroz smanjenje nivoa triglicerida, holesterola, glukoze, insulina i krvnog pritiska). DATS, najverovatnije preko kompleksnih mehanizama, koji uključuju antioksidacione, antiinflamacijske i antiapoptotske efekte ostvaruje kardioprotekciju i doprinosi u ograničavanju I/R povrede i očuvanju funkcije miokarda. Zaključak: Pokazani protektivni efekti DATS-a, od posebnog su značaja za buduća istraživanja, koja bi ispitivala dodatne terapijske mogućnosti i mehanizme koji su odgovorni za njegovu farmakološku aktivnost. Takođe, uvođenje DATS-a u terapijski algoritam može imati nesumnjiv značaj u smislu unapređenja, razumevanja i terapijske primene novih vidova prekondicioniranja u ishemijskoj bolesti srca, što bi olakšalo lečenje mnogobrojne populacije bolesnika i ujedno imalo nesumljiv ekonomski značaj.

Objective: The aim of this study was to investigate the effects of chronic administration of diallyl trisulfide (DATS), distinguished as the most potent natural donor of hydrogen sulfide isolated from garlic, in healthy, diabetic rats (DM) and metabolic syndrome (MetS) rats. The focus was to examine the cardioprotective role of DATS in ex vivo-induced myocardial ischemia-reperfusion (I/R) injury, but also to its ability to reduced symptoms of DM and MetS. Methods: This chronic, experimental study, included 72 Wistar albino rats, divided into 6 main groups: healthy rats untreated and treated with DATS (CTRL and DATS), DM rats untreated and treated with DATS (DM, DM+DATS), and MetS rats untreated and treated with DATS (MS and MS+DATS). DATS treatment consisted of three weeks per os administration of DATS every other day at a dose of 40 mg/kg. After chronic treatment, the animals were sacrificed and each of the main groups were divided into two subgroups depending on the protocol on the Langendorff apparatus (90 minutes retrograde perfusion or I/R myocardial injury). Results: DATS treatment showed significant cardioprotective effects, improved myocardial recovery and contributed to the preservation of its function after I/R injury. Also, DATS treatment significantly decreased glucose levels in DM rats, while in rats with MetS DATS treatment alleviated the symptoms of disease (reflected by a decrease in triglyceride, cholesterol, glucose, insulin and blood pressure). DATS, most likely via complex mechanisms, which include antioxidant, anti-inflammatory and anti-apoptotic effects, exerts cardioprotection and contributes to limiting I/R injury and preserving myocardial function. Conclusion: The aforementioned effects of DATS are of particular relevance for future research that would examine additional therapeutic possibilities and mechanisms responsible for its pharmacological activity. Also, the introduction of DATS into a therapeutic algorithm can be of undoubted importance in terms of understanding and therapeutic application of new types of preconditioning in ischemic heart disease, which would facilitate the treatment of a large population of patients and have unquestionable economic significance.

dialil trisulfid, dijabetes, metabolički sindrom, izolovano srce, ishemija/reperfuzija

diallyl trisulfide, diabetes, metabolic syndrome, isolated heart, ischemia/reperfusion

616.379-008.64:612.08(043.3)

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