Alleviation of Aflatoxin B1-Induced Genomic Damage by Proanthocyanidins via Modulation of DNA Repair.
In order to study the mechanisms underlying the alleviation of aflatoxin B1-induced genomic damage by proanthocyanidins (PAs), we examined the modulation of oxidative DNA damage induced by aflatoxin B1 in PAs-pretreated animals. The effects of PAs on changes in the expression of DNA damage and repair genes induced by aflatoxin B1 were also evaluated in rat marrow cells. Administration of PAs before aflatoxin B1 significantly mitigated aflatoxin B1-induced oxidative DNA damage in a dose-dependent manner. Aflatoxin B1 treatment induced significant alterations in the expression of specific DNA repair genes, and the pre-treatment of rats with PAs ameliorated the altered expression of these genes. Conclusively, PAs protect against aflatoxin B1-induced oxidative DNA damage in rats. These protective effects are attributed to the antioxidant effects of PA and enhanced DNA repair through modulation of DNA repair gene expression. Therefore, PAs are a promising chemoprotective agent for averting genotoxic risks associated with aflatoxin B1 exposure.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Saleh A
SA
Bakheet
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Ahmed M
AM
Alhuraishi
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Naif O
NO
Al-Harbi
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Khaled A
KA
Al-Hosaini
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Shakir D
SD
Al-Sharary
Department of Plant Protection, Faculty of Agriculture, Damanhour University, Damanhour, Egypt.
Mohammed M
MM
Attia
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Ali R
AR
Alhoshani
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Othman A
OA
Al-Shabanah
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Mohammed M
MM
Al-Harbi
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Faisal
F
Imam
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Sheikh F
SF
Ahmad
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Sabry M
SM
Attia
D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001231:Aspergillus flavus / Q000737:chemistry; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D018384:Oxidative Stress / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D044945:Proanthocyanidins; D016159:Tumor Suppressor Protein p53; D016604:Aflatoxin B1; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D045647:DNA Glycosylases; C483741:OGG1 protein, rat
Aflatoxins; Carcinogenesis; DNA Damage/Repair; Proanthocyanidins