Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats

Abstract

Backgroung/Aim. Since combining conventional drugs with herbal medicinal products is in current research focus and possible of great interest as therapy improvement way, the aim of this study was to determine the effects of well-established antiatherosclerotic drug atorvastatin (CAS number 134523-00-5) and commercially available artichoke leaf tincture (ALTINC), used as combined therapy, as well as to compare effects of these two treatments separately. Methods. Experimental animals were divided into five groups: the group I (the control group of rats fed with standard diet during 11 weeks), and the remaining 4 groups of rats (II, III, IV and V) fed with standard diet during the first week and then with hypercholesterolemic diet during the next 10 weeks. The group II of rats were left without treatment, while in the groups III, IV and V were rats treated per os with atorvastatin (1.15 mg/kg body wright - b.w.), ALTINC (0.1 mL/kg b.w.) and their combination in same doses, respectively, for the last six weeks. Results. The cholesterol rich diet led to pronounced hyperlipidemia which could not be overcame with the therapy. However, the therapy showed positive effects on abdominal aorta wall thickness and parameters of oxidative stress (malondialdehyde - MDA, proxidative-antioxidative balance - PAB) and anti- oxidative protection (reduced glutathione - GSH, paraoxanase 1 - PON1, superoxide dismutase - SODA SH groups), especially ALTINC was successful in oxidative status improvement. Conclusion. Separate treatments comparison showed that artichoke leaf tincture is very potent antioxidant with beneficial effects in early stages of atherosclerosis. Since atorvastatin and constituents of ALTINC probably have different mechanisms of action, simultaneous use of both therapies could be beneficial but should be further investigated since our results showed that ALTINC is less effective when used in combination with atorvastatin.

Uvod/Cilj. Savremena istraživanja sve više se okreću mogućnosti kombinovanja konvencionalne terapije sa biljnim lekovitim proizvodima. Cilj ovog istraživanja bio je praćenje efekata atorvastatina (CAS broj 134523-00-5), poznatog leka koji se koristi u terapiji hiperlipidemije, i tinkture lista artičoke primenjenih pojedinačno, kao i u obliku kombinovane terapije. Metode. Eksperimentalne životinje bile su podeljene u pet grupa: grupa I bila je kontrolna i činili su je pacovi hranjeni standardnom hranom za glodare tokom 11 nedelja, dok su preostale četiri grupe (II-V) činili pacovi koji su hranjeni standardnom hranom tokom prve nedelje, a potom u narednih 10 hranom bogatom holesterolom. Grupa II nije dobijala nikakav tretman, dok su III, IV i V posle 4. nedelje od početka uzimanja hrane bogate holesterolom, tokom narednih šest nedelja tretirane per os, redom: atorvastatinom u dozi od 1,15 mg/kg, tinkturom artičoke u dozi od 0,1 mL/kg i njihovom kombinacijom u istim dozama. Rezultati. Hrana bogata holesterolom izazvala je uznapredovalu hiperholesterolemiju na koju terapija nije značajno delovala. Terapija je pokazala povoljan efekat na debljinu zida trbušne aorte, parametre oksidativnog stresa (malondialdehid - MDA, prooksidativni-antioksidativni balans - PAB) i anti-oksidativne zaštite (redukovani glutation - GSH, SH grupe, paraoksonazu1 - PON1, superoksid dismutazu - SOD). Tinktura lista artičoke pokazala se najboljom u poboljšanju oksidativnog statusa. Zaključak. Poređenje pojedinačne terapije pokazalo je da tinktura lista artičoke ima jako anti-oksidativno dejstvo i pokazuje povoljne efekte u početnim fazama aterosklerotskog procesa. S obzirom na to da atorvastatin i komponente tinkture lista artičoke verovatno deluju različitim mehanizmima, kombinovana primena može imati povoljne efekte, ali se mora dodatno ispitati jer dobijeni rezultati ukazuju da je tinktura lista artičoke manje efikasan kada se primenjuje zajedno sa atorvastatinom.