title: Cellular protection with proanthocyanidins derived from grape seeds.
abstract: Grape seed proanthocyanidins have been reported to possess a broad spectrum of pharmacological and medicinal properties against oxidative stress. We have demonstrated that IH636 proanthocyanidin extract (GSPE) provides excellent protection against free radicals in both in vitro and in vivo models. GSPE had significantly better free radical scavenging ability than vitamins C, E and beta-carotene and demonstrated significant cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal cells. GSPE protected against tobacco-induced apoptotic cell death in human oral keratinocytes and provided protection against cancer chemotherapeutic drug-induced cytotoxicity in human liver cells by modulating cell cycle/apoptosis regulatory genes such as bcl2, p53 and c-myc. Recently, the bioavailability and mechanistic pathways of cytoprotection by GSPE were examined on acetaminophen-induced hepatotoxicity and nephrotoxicity, amiodarone-induced pulmonary toxicity, doxorubicin-induced cardiotoxicity, DMN-induced immunotoxicity and MOCAP-induced neurotoxicity in mice. Serum chemistry changes, integrity of genomic DNA and histopathology were assessed. GSPE pre-exposure provided near complete protection in terms of serum chemistry changes and DNA damage, as well as abolished apoptotic and necrotic cell death in all tissues. Histopathological examination reconfirmed these findings. GSPE demonstrated concentration-/dose-dependent inhibitory effects on the drug metabolizing enzyme cytochrome P450 2E1, and this may be a major pathway for the anti-toxic potential exerted by GSPE. Furthermore, GSPE treatment significantly decreased TNFalpha-induced adherence of T-cells to HUVEC by inhibiting VCAM-1 expression. These results demonstrate that GSPE is highly bioavailable and may serve as a potential therapeutic tool in protecting multiple target organs from structurally diverse drug- and chemical-induced toxicity.
authors.affiliation: Department of Pharmacy Services, Creighton University School of Pharmacy & Allied Health Professions, Omaha, Nebraska 68178, USA. debsis@creighton.edu
authors.forename: Debasis
authors.initials: D
authors.lastname: Bagchi
authors.forename: Manashi
authors.initials: M
authors.lastname: Bagchi
authors.forename: Sidney j
authors.initials: Sj
authors.lastname: Stohs
authors.forename: Sidhatha D
authors.initials: SD
authors.lastname: Ray
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Sen
authors.forename: Harry G
authors.initials: HG
authors.lastname: Preuss
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D019610:Cytoprotection; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D044945:Proanthocyanidins; D012639:Seeds / Q000737:chemistry; D027843:Vitis
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; D016166:Free Radical Scavengers; D044945:Proanthocyanidins; C013221:proanthocyanidin