N-Acetyl Cysteine Treatment Restores Early Phase Fracture Healing in Ethanol-Fed Rats

Michael J. Duryee, Anand Dusad, Carlos D. Hunter, Kusum Kharbanda, Joseph D. Bruenjes, Karen C. Easterling, Justin C Siebler, Geoffrey Milton Thiele, Dennis A. Chakkalakal

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Fracture healing in alcoholics is delayed and often associated with infections resulting in prolonged rehabilitation. It has been reported that binge drinking of alcohol increases oxidative stress and delays fracture healing in rats, which is prevented by treatment with the antioxidant n-acetyl cysteine (NAC). Oxidative stress is a significant factor in pathologies of various organs resulting from chronic alcoholism. Therefore, we hypothesize that treatment with NAC reduces oxidative stress and restores fracture healing in chronic alcoholics. Methods: Rats (10 months old) were pair-fed the Lieber-DeCarli ethanol (EtOH) diet or control diet for 16 weeks. A closed fracture was performed and rats allowed to recover for 72 hours. Rats were divided into 4 groups—control, control + NAC, EtOH, and EtOH + NAC—and injected intraperitoneally with 200 mg/kg of NAC daily for 3 days. Serum and bone fracture callus homogenates were collected and assayed for traditional markers of inflammation, oxidative stress, and bone regeneration. Results: The oxidative stress marker malondialdehyde (MDA) was increased in both serum and bone tissue in EtOH-fed animals compared to controls. NAC treatment significantly (p < 0.01) reduced MDA to near normal levels and dramatically increased the index of antioxidant efficacy (catalase/MDA ratio) (p < 0.01). Inflammatory markers tumor necrosis factor-α, interferon-γ, and interleukin-6 were significantly decreased in serum and callus following NAC treatment. NAC treatment reduced EtOH-induced bone resorption as evidenced by significant decreases in C-telopeptide of type-I-collagen levels (p < 0.05) and band-5 tartrate-resistant acid phosphatase levels in the tissue (p < 0.001). Conclusions: Oxidative stress and excessive inflammation are involved in the inhibition of fracture healing by EtOH. In this study, early short-term treatment of EtOH-fed animals with the antioxidant NAC reduced oxidative stress and normalized the innate immune response to fracture in the early phase of fracture healing, thereby restoring the normal onset of bone regeneration.

Original languageEnglish (US)
Pages (from-to)1206-1216
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume42
Issue number7
DOIs
StatePublished - Jul 2018

Fingerprint

Acetylcysteine
Fracture Healing
Oxidative stress
Cysteine
Rats
Ethanol
Oxidative Stress
Bone
Malondialdehyde
Stress Fractures
Bone Regeneration
Antioxidants
Bony Callus
Therapeutics
Alcoholics
Nutrition
Animals
Serum
Tissue
Diet

Keywords

  • Alcoholic Liver Disease
  • Antioxidants
  • Ethanol
  • Fracture Model
  • Inflammation
  • N-Acetyl Cysteine
  • Rat Model
  • Reactive Oxygen Species

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Duryee, M. J., Dusad, A., Hunter, C. D., Kharbanda, K., Bruenjes, J. D., Easterling, K. C., ... Chakkalakal, D. A. (2018). N-Acetyl Cysteine Treatment Restores Early Phase Fracture Healing in Ethanol-Fed Rats. Alcoholism: Clinical and Experimental Research, 42(7), 1206-1216. https://doi.org/10.1111/acer.13765

N-Acetyl Cysteine Treatment Restores Early Phase Fracture Healing in Ethanol-Fed Rats. / Duryee, Michael J.; Dusad, Anand; Hunter, Carlos D.; Kharbanda, Kusum; Bruenjes, Joseph D.; Easterling, Karen C.; Siebler, Justin C; Thiele, Geoffrey Milton; Chakkalakal, Dennis A.

In: Alcoholism: Clinical and Experimental Research, Vol. 42, No. 7, 07.2018, p. 1206-1216.

Research output: Contribution to journalArticle

Duryee, Michael J. ; Dusad, Anand ; Hunter, Carlos D. ; Kharbanda, Kusum ; Bruenjes, Joseph D. ; Easterling, Karen C. ; Siebler, Justin C ; Thiele, Geoffrey Milton ; Chakkalakal, Dennis A. / N-Acetyl Cysteine Treatment Restores Early Phase Fracture Healing in Ethanol-Fed Rats. In: Alcoholism: Clinical and Experimental Research. 2018 ; Vol. 42, No. 7. pp. 1206-1216.
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AU - Dusad, Anand

AU - Hunter, Carlos D.

AU - Kharbanda, Kusum

AU - Bruenjes, Joseph D.

AU - Easterling, Karen C.

AU - Siebler, Justin C

AU - Thiele, Geoffrey Milton

AU - Chakkalakal, Dennis A.

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N2 - Background: Fracture healing in alcoholics is delayed and often associated with infections resulting in prolonged rehabilitation. It has been reported that binge drinking of alcohol increases oxidative stress and delays fracture healing in rats, which is prevented by treatment with the antioxidant n-acetyl cysteine (NAC). Oxidative stress is a significant factor in pathologies of various organs resulting from chronic alcoholism. Therefore, we hypothesize that treatment with NAC reduces oxidative stress and restores fracture healing in chronic alcoholics. Methods: Rats (10 months old) were pair-fed the Lieber-DeCarli ethanol (EtOH) diet or control diet for 16 weeks. A closed fracture was performed and rats allowed to recover for 72 hours. Rats were divided into 4 groups—control, control + NAC, EtOH, and EtOH + NAC—and injected intraperitoneally with 200 mg/kg of NAC daily for 3 days. Serum and bone fracture callus homogenates were collected and assayed for traditional markers of inflammation, oxidative stress, and bone regeneration. Results: The oxidative stress marker malondialdehyde (MDA) was increased in both serum and bone tissue in EtOH-fed animals compared to controls. NAC treatment significantly (p < 0.01) reduced MDA to near normal levels and dramatically increased the index of antioxidant efficacy (catalase/MDA ratio) (p < 0.01). Inflammatory markers tumor necrosis factor-α, interferon-γ, and interleukin-6 were significantly decreased in serum and callus following NAC treatment. NAC treatment reduced EtOH-induced bone resorption as evidenced by significant decreases in C-telopeptide of type-I-collagen levels (p < 0.05) and band-5 tartrate-resistant acid phosphatase levels in the tissue (p < 0.001). Conclusions: Oxidative stress and excessive inflammation are involved in the inhibition of fracture healing by EtOH. In this study, early short-term treatment of EtOH-fed animals with the antioxidant NAC reduced oxidative stress and normalized the innate immune response to fracture in the early phase of fracture healing, thereby restoring the normal onset of bone regeneration.

AB - Background: Fracture healing in alcoholics is delayed and often associated with infections resulting in prolonged rehabilitation. It has been reported that binge drinking of alcohol increases oxidative stress and delays fracture healing in rats, which is prevented by treatment with the antioxidant n-acetyl cysteine (NAC). Oxidative stress is a significant factor in pathologies of various organs resulting from chronic alcoholism. Therefore, we hypothesize that treatment with NAC reduces oxidative stress and restores fracture healing in chronic alcoholics. Methods: Rats (10 months old) were pair-fed the Lieber-DeCarli ethanol (EtOH) diet or control diet for 16 weeks. A closed fracture was performed and rats allowed to recover for 72 hours. Rats were divided into 4 groups—control, control + NAC, EtOH, and EtOH + NAC—and injected intraperitoneally with 200 mg/kg of NAC daily for 3 days. Serum and bone fracture callus homogenates were collected and assayed for traditional markers of inflammation, oxidative stress, and bone regeneration. Results: The oxidative stress marker malondialdehyde (MDA) was increased in both serum and bone tissue in EtOH-fed animals compared to controls. NAC treatment significantly (p < 0.01) reduced MDA to near normal levels and dramatically increased the index of antioxidant efficacy (catalase/MDA ratio) (p < 0.01). Inflammatory markers tumor necrosis factor-α, interferon-γ, and interleukin-6 were significantly decreased in serum and callus following NAC treatment. NAC treatment reduced EtOH-induced bone resorption as evidenced by significant decreases in C-telopeptide of type-I-collagen levels (p < 0.05) and band-5 tartrate-resistant acid phosphatase levels in the tissue (p < 0.001). Conclusions: Oxidative stress and excessive inflammation are involved in the inhibition of fracture healing by EtOH. In this study, early short-term treatment of EtOH-fed animals with the antioxidant NAC reduced oxidative stress and normalized the innate immune response to fracture in the early phase of fracture healing, thereby restoring the normal onset of bone regeneration.

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KW - N-Acetyl Cysteine

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KW - Reactive Oxygen Species

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