Protective effect of guggulsterone against cardiomyocyte injury induced by doxorubicin in vitro

Abstract

BackgroundDoxorubicin (DOX) is an effective antineoplastic drug; however, clinical use of DOX is limited by its dose-dependent cardiotoxicity. It is well known that reactive oxygen species (ROS) play a vital role in the pathological process of DOX-induced cardiotoxicity. For this study, we evaluated the protective effects of guggulsterone (GS), a steroid obtained from myrrh, to determine its preliminary mechanisms in defending against DOX-induced cytotoxicity in H9C2 cells.MethodsIn this study, we used a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release measurements, and Hoechst 33258 staining to evaluate the protective effect of GS against DOX-induced cytotoxicity in H9C2 cells. In addition, we observed the immunofluorescence of intracellular ROS and measured lipid peroxidation, caspase-3 activity, and apoptosis-related proteins by using Western blotting.ResultsThe MTT assay and LDH release showed that treatment using GS (1–30 μM) did not cause cytotoxicity. Furthermore, GS inhibited DOX (1 μM)-induced cytotoxicity in a concentration-dependent manner. Hoechst 33258 staining showed that GS significantly reduced DOX-induced apoptosis and cell death. Using GS at a dose of 10–30 μM significantly reduced intracellular ROS and the formation of MDA in the supernatant of DOX-treated H9C2 cells and suppressed caspase-3 activity to reference levels. In immunoblot analysis, pretreatment using GS significantly reversed DOX-induced decrease of PARP, caspase-3 and bcl-2, and increase of bax, cytochrome C release, cleaved-PARP and cleaved-caspase-3. In addition, the properties of DOX-induced cancer cell (DLD-1 cells) death did not interfere when combined GS and DOX.ConclusionThese data provide considerable evidence that GS could serve as a novel cardioprotective agent against DOX-induced cardiotoxicity.

The Oleo-Gum-Resin of Commiphora myrrha Ameliorates Male Reproductive Dysfunctions in Streptozotocin-Induced Hyperglycemic Rats

“…There is evidence showing that the use of guggulsterone at the doses of 10-30 μM significantly reduced the formation of MDA and suppressed caspase-3 activity to reference levels in doxorubicin-induced cytotoxicity and cell death in H9C2 cell line. 36 The beneficial effects of EEM found in the present study might be attributed to its phytochemical compounds.…”

Organ-specific antitoxic effects of N-stearoilethanolamine male mice with lewis carcinoma under indoxorubicin intoxication

“…Відомо, що важливу роль у розвитку кардіотоксичності, зумовленої доксорубіцином, відіграють активні форми кисню (АФК) [1]. Одним із механізмів пошкоджень міокарда доксорубіцином є роз-балансування активності антиоксидантних ензимів у тканині серця, зокрема каталази, глутатіонпероксидази та супероксиддисмутази [2].…”

Therapeutic Effect of Guggulsterone in Primary Cultured Orbital Fibroblasts Obtained From Patients with Graves’ Orbitopathy

“…10 GS has aroused considerable interest as an active gugulipid component, exerting diverse pharmacologic reactions, including anti-inflammatory, hypolipidemic, antineoplastic, antioxidative, antidiabetic, and cardioprotective effects. 9,[21][22][23][24][25][26] In this study, we illustrate the significant ability of GS to suppress the elevated production of proinflammatory mediators in IL-1β-stimulated GO and non-GO fibroblasts. Additionally, GS attenuated adipogenesis and hyaluronan production.…”