Premium
Evaluation of Tumor Necrosis Factor Alpha (TNF‐α) in Sleep‐Deprived Menopausal‐Induced Rats and the Impact on Bone Health
Author(s) -
Ellsworth Nicole Lynn,
Frisch Frank
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09173
Subject(s) - ovariectomized rat , medicine , tumor necrosis factor alpha , osteoporosis , endocrinology , sleep deprivation , intraperitoneal injection , estrogen , saline , sleep (system call) , circadian rhythm , computer science , operating system
Post‐menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro‐inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zoledronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zoledronate on the concentrations of tumor necrosis factor alpha‐type (TNF‐α) in 32 ovariectomized Wistar rats that were ovariectomized to simulate post‐menopausal estrogen‐deficiency. After one week of surgical recovery, rats were separated into 4 groups. The control group (C, n=4) was given an intraperitoneal (IP) injection of 0.45 mL of 0.9% saline, were housed in standard conditions permitting 12 hours light and 12 hours dark. The Zoledronate group (Z, n=8) were given an IP injection of 50 ug/kg of 10% Zoledronate and housed in standard conditions with a 12 hour light/dark cycle. The sleep‐deprived group (SD, n=8) were given the same IP injection as the rats in C, but were housed in chambers that did not permit sleep for 18 hours, then moved to sleep chambers for 6 hours. The sleep‐deprived Zoledronate group experienced the same sleep deprivation as the SD group, but received an IP injection of 50ug/kg body weight of 10% Zoledronate. Throughout the five‐week period of sleep deprivation cycles, the concentrations of TNF‐α were collected and examined. It was originally hypothesized that the sleep‐deprived group of rats would have the highest concentration of TNF‐α due to the biological stress associated with insomnia. However, TNF‐α levels were significantly higher in the Zoledronate group than both the control and sleep‐deprived groups, as well as the sleep‐deprived with Zoledronate groups (p<0.01). We ascribe this to bisphosphonate induced transient fever seen in Zoledronate usage in previous studies (Dicuonzo, 2003). It is also suspected that the low concentrations of TNF‐α in the sleep‐deprived groups are seen due to the short time frame of this experiment along with a challenged immune system in the animals. With a longer period of sleep deprivation, it is possible that the hypothesized cytokine levels would be reached. Support or Funding Information This study was supported in part by Novartis, Basel, Switzerland