Curcumin reduces oxidative and nitrative DNA damage through balancing of oxidant–antioxidant status in hamsters infected with Opisthorchis viverrini

Abstract

Opisthorchis viverrini (OV) infection is endemic in northeastern Thailand. We have previously reported that OV infection induces oxidative and nitrative DNA damage via chronic inflammation, which contributes to the disease and cholangiocarcinogenesis. Here, we examined the effect of curcumin, an antioxidant, on pathogenesis in OV-infected hamsters. DNA lesions were detected by double immunofluorescence and the hepatic expression of oxidant-generating and antioxidant genes was assessed by quantitative RT-PCR analysis. Dietary 1.0% curcumin significantly decreased OV-induced accumulation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidative DNA lesion, and 8-nitroguanine, a nitrative DNA lesion, in the nucleus of bile duct epithelial and inflammatory cells. Expression of oxidant-generating genes (inducible nitric oxide synthase; iNOS, its nuclear transcriptional factor, NF-kappaB, and cyclooxygenase-2), and plasma levels of nitrate, malondialdehyde, and alanine aminotransferase, were also decreased in curcumin-treated group. In contrast, curcumin increased the mRNA expression of antioxidant enzymes (Mn-superoxide dismutase and catalase), and ferric-reducing anti-oxidant power in the plasma. In conclusion, curcumin reduced oxidative and nitrative DNA damage by suppression of oxidant-generating genes and enhancement of antioxidant genes, leading to inhibition of oxidative and nitrative stress. Therefore, curcumin may be used as a chemopreventive agent to reduce the severity of OV-associated diseases and the risk of cholangiocarcinoma (CCA).

Indirect effect of a turmeric diet: enhanced bile duct proliferation in Syrian hamsters with a combination of partial obstruction by Opisthorchis viverrini infection and inflammation by N-nitrosodimethylamine administration

“…Many people are opting to choose new therapeutic methods of treatment for cancer, the most popular of which are traditional medicines. Curcumin, the primary active com- pound of TUR, has been used for many years and is effective against many diseases (Angelo and Kurzrock 2009;Half and Arber 2009;Suzuki et al 2009), including opisthorchiasis (Boonjaraspinyo et al 2009;Pinlaor et al 2009). Opisthorchiasis is a major risk factor for CCA development in Southeast Asia, especially Thailand, Laos, and Cambodia (IARC 1994;Sripa et al 2007).…”

Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells

“…This compound is well known for its antioxidant properties acting as a free radical scavenger by inhibiting lipid peroxidation and oxidative DNA damage [45], [46]. Additionally, it has been proposed that curcumin-induced apoptosis might be triggered by ROS production and/or oxidative stress in some tumor cells [47].…”

Redox regulation in health and disease — Therapeutic potential of berberine

“…It is desirable then to choose therapies on the basis of their ability to target and stabilize the activity of oxidant and antioxidant enzymes, intercede pathophysiological ROS signals, and restore homeostatic redox regulation (Ceriello & Testa, 2009;Kizhakekuttu & Widlansky, 2010;Singh, Chandra, Mahdi, Roy, & Sharma, 2010). Many natural compounds, some of which are also direct antioxidants, have been shown to display such bioactivity (Pinlaor et al, 2009;Sangeetha & Baskaran, 2010;Singh et al, 2010). One such compound is berberine, a naturally derived lipophilic isoquinoline alkaloid.…”