The reductive metabolism of nitric oxide in hepatocytes: possible interaction with thiols.
نویسندگان
چکیده
Nitric oxide (NO) is both an endogenously generated species and the active species released from a variety of important drugs. Due to its endogenous generation and use as a therapeutic agent, the metabolism and fate of NO is of interest and concern. To date, most attention regarding the metabolism and fate of NO has been paid to its oxidized metabolites. Due to the reducing environment of cells, we considered that NO may also undergo reductive metabolism as well. Therefore, we have examined the reductive metabolism of NO by hepatocytes. Generation of nitrous oxide (N(2)O) was used as an indication of NO reduction. Indeed, we observed that NO could be reduced to N(2)O by the cytosolic fraction of hepatocytes. The N(2)O production was partially inhibited by the thiol modifying agent, N-ethylmaleimide and thiol consumption was observed during N(2)O formation. Thus, our results indicate that NO reduction is feasible and likely occurs via a thiol-dependent process.
منابع مشابه
Metabolism and Cytotoxic Mechanisms of Nitroglycerin in Isolated Rat Hepatocytes
It has been proposed that organic nitrates such as glyceryl trinitrate (GTN), used in the treatment of cardiovascular diseases, act by producing nitric oxide (NO). However, the biochemical pathway for NO formation from GTN is not well understood. In the present study, we showed that nitrate formation from GTN, by isolated rat hepatocytes, was inhibited about 50% when cellular glutathione w...
متن کاملThe Effects of Cholestasis and Cirrhosis on Gastric Acid and Pepsin Secretions in Rat: Involvement of Nitric Oxide
Objective(s) The liver has major role in the organism homeostasis, interactions with other systems, synthesis and metabolism of bile production, drug detoxification and hormone inactivation. Cholestasis can be defined as an impairment of the bile flow which can lead to hepatocytes necrosis and finally cirrhosis. Some studies reported a gastric acid secretion reduction in cirrhotic subjects, wh...
متن کاملNephrotoxicity of Isosorbide Dinitrate and Cholestasis in Rat: The Possible Role of Nitric Oxide
Background: Nitric oxide (NO), a major chemical form of endothelium-derived relaxing factor and an important regulator of vascular tone, is released by endothelial cells. The role of NO is not restricted to the vascular system, and it participates in the regulation of renal hemodynamics and renal excretory function. There are increasing evidences indicating that the elevated levels of NO play a...
متن کاملImprovement of Tissue Survival of Skin Flaps by 5α-Reductase Inhibitors: Possible Involvement of Nitric Oxide and Inducible Nitric Oxide Synthase
Background: Skin flap grafting is a popular approach for reconstruction of critical skin and underlying soft tissue injuries. In a previous study, we demonstrated the beneficial effects of two 5α-reductase inhibitors, azelaic acid and finasteride, on tissue survival in a rat model of skin flap grafting. In the current study, we investigated the involvement of nitric oxide and inducible nitric o...
متن کاملMetabolism of S-nitrosoglutathione by endothelial cells.
S-nitrosoglutathione (GSNO) is an inhibitor of platelet aggregation and has also been shown to protect the ischemic heart from reperfusion-mediated injury. Although GSNO is often used in cell culture as a source of nitric oxide, the mechanisms of GSNO metabolism are not well established. We show here that GSNO decomposition by bovine aortic endothelial cells has an absolute dependence on the pr...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Drug metabolism and disposition: the biological fate of chemicals
دوره 27 9 شماره
صفحات -
تاریخ انتشار 1999