N‐acetyl‐L‐cysteine ameliorates gestational diabetes mellitus by inhibiting oxidative stress

Abstract

Gestational diabetes mellitus (GDM) is a common pregnant disorder that needs careful medical attention. N‐acetyl‐L‐cysteine (NAC) is a well‐recognized antioxidant to treat oxidative stress‐induced diseases. Although its role in GDM has been reported, the mechanism remains largely unknown. Therefore, our current study further explored its protective role against GDM. An 8‐week‐old, db/+, female mice were injected with a single dose of 100 mg/kg streptozotocin (STZ) to induce diabetes. Pregnant mice were randomly treated with 1200 mg/kg NAC or water daily. On gestational day 19, oral glucose tolerance test was performed, and visceral fat tissue and blood samples were collected. After delivery, litter size and weight were recorded. NAC could effectively improve GDM‐induced glucose intolerance, hyperlipidemia, activated inflammation, and oxidative stress in GDM mice. Moreover, NAC reduced the litter size and weight of GDM mice. NAC also activated the nuclear factor‐erythroid factor 2‐related factor 2 (Nrf2)/heme oxygenase‐1 (HO‐1) signaling pathway in the liver of GDM mice. NAC effectively ameliorated GDM symptoms and the reproductive outcome of GDM mice through inhibiting oxidative stress, inflammation, and hyperlipidemia. Therefore, NAC might serve as a potential candidate drug against GDM.

NRF2 Dysregulation in Mice Leads to Inadequate Beta-Cell Mass Expansion during Pregnancy and Gestational Diabetes

“…Notably, prevention of GDM using broad spectrum antioxidants is still controversial. Accordingly, while treatment with N-Acetyl-l-cysteine (NAC), vitamin E and vitamin C have been reported to ameliorate diabetes in GDM and type 2 diabetic mouse models [37][38][39][40][41] , clinical trials in women with GDM are still lacking and administration of NAC to type 2 diabetic patients did not improve their glycemia 42 . This could result from differences in the physiology between rodents and humans.…”

Development of Dipeptide N–acetyl–L–cysteine Loaded Nanostructured Carriers Based on Inorganic Layered Hydroxides

“…NAC has effective antioxidant properties and, consequently, a strong capability to be used in treatments related to the generation of free radicals and as a food supplement. This drug has therapeutic potential for the treatment of other diseases such as Alzheimer’s [ 6 ], type-2 diabetes [ 7 ], type-1 diabetes [ 8 ], gestational diabetes mellitus [ 9 ], diseases related to psychiatric disorders [ 10 ], neurodegenerative diseases [ 11 ], inhibition and induced death of lung cancer cells [ 12 ], HIV-associated tuberculosis [ 13 ], and bone regeneration approaches [ 14 , 15 ]. NAC is considered helpful in the nutraceutical control of RNA viruses such as influenza and coronavirus and has been investigated as an adjuvant to the prevention and therapy of COVID-19 [ 16 , 17 , 18 ] and post-COVID-19 pulmonary fibrosis [ 19 ].…”