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NAD+ AND Dunnione

Saeed Nazari Soltan Ahmad, Nadereh Rashtchizadeh, Hassan Argani, Leila Roshangar, Amir Ghorbani Haghjo, Davoud Sanajou, Fatemeh Panah, Zahra Ashrafi Jigheh, Siavoush Dastmalchi, Mehran Mesgari-Abbasi
Despite being an efficacious anticancer agent, the clinical utility of cisplatin is hindered by its cardinal side effects. This investigation aimed to appraise potential protective impact of dunnione, a natural naphthoquinone pigment with established NQO1 stimulatory effects, on cisplatin nephrotoxicity of rats. Dunnione was administered orally at 10 and 20 mg/kg doses for 4 d and a single injection of cisplatin was delivered at the second day. Renal histopathology, inflammatory/oxidative stress/apoptotic markers, kidney function, and urinary markers of renal injury were assessed...
June 4, 2018: Free Radical Research
Arpana Pandit, Hyung-Jin Kim, Gi-Su Oh, AiHua Shen, Su-Bin Lee, Dipendra Khadka, SeungHoon Lee, Hyeok Shim, Sei-Hoon Yang, Eun-Young Cho, Kang-Beom Kwon, Tae Hwan Kwak, Seong-Kyu Choe, Raekil Park, Hong-Seob So
Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD(+)) is a cofactor for various enzymes associated with cellular homeostasis...
November 27, 2015: Biochemical and Biophysical Research Communications
Hyung-Jin Kim, Arpana Pandit, Gi-Su Oh, AiHua Shen, Su-Bin Lee, Dipendra Khadka, SeungHoon Lee, Hyeok Shim, Sei-Hoon Yang, Eun-Young Cho, Tae Hwan Kwak, Seong-Kyu Choe, Raekil Park, Hong-Seob So
Ototoxicity is an important issue in patients receiving cisplatin chemotherapy. Numerous studies have demonstrated that cisplatin-induced ototoxicity is related to oxidative stress and DNA damage. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as an important regulator of energy metabolism and cellular homeostasis. Here, we demonstrate that the levels and activities of sirtuin-1 (SIRT1) are suppressed by the reduction of intracellular NAD(+) levels in cisplatin-mediated ototoxicity...
March 2016: Hearing Research
Jinlei Bian, Lili Xu, Bang Deng, Xue Qian, Jun Fan, Xiuwen Yang, Fang Liu, Xiaoli Xu, Xiaoke Guo, Xiang Li, Haopeng Sun, Qidong You, Xiaojin Zhang
Natural product (±)-dunnione (2) and its ortho-quinone analogues (3-8) were synthesized and found to be substrates for NQO1. The structure-activity relationship study revealed that the biological activity was favored by the presence of methyl group at the C ring and methoxy group at the A ring. The docking studies supported the rationalization of the metabolic studies. Deeper location in the active site of NQO1, interactions with hydrophobic pocket and C-H…π interactions with the adjacent Phe178 residue contributed to the better catalytic efficiency and specificity to NQO1...
March 15, 2015: Bioorganic & Medicinal Chemistry Letters
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