Attenuation of genotoxicity, oxidative stress, apoptosis and inflammation by rutin in benzo(a)pyrene exposed lungs of mice: plausible role of NF-κB, TNF-α and Bcl-2.

Abstract

BACKGROUND:

Benzo(a)pyrene [B(a)P] is an environmental contaminant and potential carcinogenic agent that causes lung injuries which leads to lung cancer. Rutin, a well-known flavonoid present in various natural sources, possesses biological activities such as anti-oxidative and anti-inflammatory properties. The aim of this study was to evaluate the protective effects of rutin against B(a)P-induced genotoxicity, oxidative stress, apoptosis and inflammation in Swiss albino mice.

METHODS:

Pretreatment of rutin was given by oral gavage at doses of 40 and 80 mg/kg body weight (b.wt.) for 7 days before the administration of a single oral dose of B(a)P (125 mg/kg b.wt.). The ameliorative effect of rutin on oxidative stress, apoptotic and inflammatory markers in lung tissues and genotoxicity was studied using an alkaline unwinding assay and DNA fragmentation.

RESULTS:

B(a)P enhanced lipid peroxidation, xanthine oxidase, H2O2 generation and lactate dehydrogenase (LDH) activity; depleted activities of anti-oxidant enzymes and glutathione content; induced DNA strand breaks and fragmentation; disrupted normal histopathological architecture and also showed abnormal expression of NF-κB, COX-2, IL-6, TNF-α and Bcl-2. Rutin pretreatment caused a significant reduction in lipid peroxidation and LDH activity; increased glutathione content; restored antioxidant enzyme activity; reduced DNA strand breaks and fragmentation; modulated the expression of inflammatory, and apoptotic markers and restored the histopathological structure.

CONCLUSIONS:

The findings of the present study supported the protective effect of rutin against B(a)P-induced lung toxicity and genotoxicity.

• Authors: Ayaz Shahid, Rashid Ali, Nemat Ali, Syed Kazim Hasan, Summya Rashid, Ferial Majed, Sarwat Sultana
• Journal: Journal of complementary & integrative medicine (J Complement Integr Med) Vol. 13 Issue 1 Pg. 17-29 (Mar 2016) ISSN: 1553-3840 [Electronic] Germany
• PMID: 26829483 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Carcinogens
• Interleukin-6
• NF-kappa B
• Proto-Oncogene Proteins c-bcl-2
• Tumor Necrosis Factor-alpha
• Benzo(a)pyrene
• Malondialdehyde
• Rutin
• DNA
• Hydrogen Peroxide
• L-Lactate Dehydrogenase
• Cyclooxygenase 2
• Superoxide Dismutase

Topics

• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Benzo(a)pyrene (toxicity)
• Carcinogens (toxicity)
• Cyclooxygenase 2 (metabolism)
• DNA (drug effects)
• Hydrogen Peroxide (metabolism)
• Interleukin-6 (metabolism)
• L-Lactate Dehydrogenase (drug effects)
• Male
• Malondialdehyde (metabolism)
• Mice
• NF-kappa B (metabolism, physiology)
• Oxidative Stress (physiology)
• Pneumonia (prevention & control)
• Proto-Oncogene Proteins c-bcl-2 (metabolism, physiology)
• Rutin (pharmacology)
• Superoxide Dismutase (drug effects)
• Tumor Necrosis Factor-alpha (metabolism, physiology)