Protective effect of gallic acid against bleomycin-induced pulmonary fibrosis in rats.
BACKGROUND
Bleomycin (BLM), a chemotherapeutic agent is indicated in the management of some types of cancers. This drug produces a dose-dependent pulmonary fibrosis (PF) in most patients as well as experimental animals through oxidative injury. This study aimed to investigate the effect of gallic acid (GA), a polyphenolic compound, against PF-induce by BLM in rats.


METHODS
The rats were given GA orally at doses (50, 100, and 200 mg/kg/day) for 7 consecutive days before the administration of single intratracheal (it) instillation of BLM at 7.5 IU/kg. GA doses were continued for 21 days after BLM exposure. The regulatory effects of GA on BLM-induced pulmonary toxicity were determined by assaying oxidative stress biomarkers, lung and serum cytokine levels, and by histopathological examination of lung tissue.


RESULTS
The results showed that intratracheal BLM administration significantly increased the inflammatory or fibrotic changes, collagen content, levels of malondialdehyde (MDA), and pro-inflammatory cytokines such as TNF-α and IL1β in lung. Also, it significantly decreased non-enzymatic (total thiol) and enzymatic (glutathione peroxidase (GPx)) antioxidant contents in the rats' lung tissue. However, oral administration of GA reversed all of these biochemical indices as well as histopathological alterations induced by BLM.


CONCLUSIONS
Results of the present study demonstrate that GA, by its antioxidant properties, attenuates oxidative damage and fibrosis induced by BLM. Thus, an effective supplement with GA as an adjuvant therapy may be a very promising compound in reducing the side effects of BLM.
Department of Pharmacology and Toxicology, School of Pharmacy, Medicinal Plants and Natural Products Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Jafar
J
Nikbakht
Department of Pharmacology and Toxicology, School of Pharmacy, Medicinal Plants and Natural Products Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Ali Asghar
AA
Hemmati
Department of Pharmacology and Toxicology, School of Pharmacy, Medicinal Plants and Natural Products Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Ardeshir
A
Arzi
Department of Pharmacology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: mansouri_smt@yahoo.com.
Mohammad Taghi
MT
Mansouri
Department of Pathobiology, School of Veterinary Medicine, University of Shahid Chamran, Ahvaz, Iran.
Anahita
A
Rezaie
Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Mehri
M
Ghafourian
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001761:Bleomycin; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats
D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D001761:Bleomycin; D005707:Gallic Acid; D006909:Hydroxyproline
Bleomycin; Gallic acid; Oxidative stress; Pulmonary fibrosis; Rats