Curcumin Ameliorates Benzo[a]pyrene-Induced DNA Damages in Stomach Tissues of Sprague-Dawley Rats.

Kyeong Seok Kim,Yoon Gyoon Kim,Hye Gwang Jeong,Boomin Kim,Jae Hyeon Park,Hyung Sik Kim,Ji Yeon Son,Su Hyun Lee,Hae Ri Kim,Byung Mu Lee,Na Yoon Kim

doi:10.3390/ijms20225533

Kyeong Seok Kim, Yoon Gyoon Kim + Show 9 more

Open Access

https://doi.org/10.3390/ijms20225533

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Abstract

Benzo[a]pyrene (BaP) is a well-known carcinogen formed during the cooking process. Although BaP exposure has been implicated as one of the risk factors for lung cancer in animals and humans, there are only limited data on BaP-induced gastrointestinal cancer. Therefore, this study investigated the protective effects of curcumin on BaP-induced DNA damage in rat stomach tissues. BaP (20 mg/kg/day) and curcumin (50, 100, or 200 mg/kg) were administered daily to Sprague-Dawley rats by oral gavage over 30 days. Curcumin was pre-administered before BaP exposure. All rats were euthanized, and liver, kidney, and stomach tissues were removed at 24 h after the last treatment. We observed that aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glucose levels were significantly reduced in rats treated with high dose co-administration of curcumin (200 mg/kg) compared to BaP alone. The expression levels of cytochrome P450 (CYP) 1A1 and CYP1B1 were significantly increased in the liver of rats treated with BaP. However, co-administration of curcumin (200 mg/kg) with BaP markedly reduced CYP1A1 expression in a dose-dependent manner. Furthermore, plasma levels of BaP-diolepoxide (BPDE) and BaP metabolites were significantly reduced by co-administration of curcumin (200 mg/kg). Additionally, co-administration of curcumin (200 mg/kg) with BaP significantly reduced the formation of BPDE-I-DNA and 8-hydroxydeoxy guanosine (8-OHdG) adducts in the liver, kidney, and stomach tissues. The inhibition of these adduct formations were more prominent in the stomach tissues than in the liver. Overall, our observations suggest that curcumin might inhibit BaP-induced gastrointestinal tumorigenesis and shows promise as a chemopreventive agent.

Highlights

Benzo[a]pyrene (BaP) is considered a major pollutant in the environment
Animals treated with either BaP or BaP in combination with curcumin exhibited a slight, but significant reduction in body weight compared to controls
Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, as well as blood urea nitrogen (BUN) and glucose levels, were significantly increased in the BaP-treated group compared with control group

Summary

Introduction

Benzo[a]pyrene (BaP) is considered a major pollutant in the environment. BaP is a polyaromatic hydrocarbon (PAH) found in coal tar, coal-processing waste products, petroleum sludge, asphalt, and tobacco smoke [1,2]. Exposure to BaP causes various adverse health effects including cancer development, immunosuppression, teratogenicity, and hormonal dysfunctions [3,4]. With the exception of occupational exposure, the major route of BaP exposure to human is via contaminated foods because BaP can be produced by the pyrolysis of amino acids, fatty acids, and carbohydrates during the cooking process [5,6]. The probability of BaP exposure to humans through the consumption of grilled meats, water, and smoked fishes is very high [7,8]. In addition to specific components of the diet, the cooking process is associated with increased risk of gastrointestinal cancer, which is causatively related to the formation of BaP-DNA adducts in the stomach [9,10,11].

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