Short-Term Cohousing of Sick with Healthy or Treated Mice Alleviates the Inflammatory Response and Liver Damage
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ORIGINAL ARTICLE
Short-Term Cohousing of Sick with Healthy or Treated Mice Alleviates the Inflammatory Response and Liver Damage Yehudit Shabat,1 Yoav Lichtenstein,1 and Yaron Ilan
1,2
(Received May 1, 2020; accepted September 22, 2020)
Cohousing of sick with healthy or treated animals is based on the concept of sharing an intestinal ecosystem and coprophagy, the consumption of feces, which includes sharing of the microbiome and of active drug metabolites secreted in the feces or urine. To develop a model for short-term cohousing, enabling the study of the effect of sharing an ecosystem on inflammatory states. To determine the impact of cohousing of sick and healthy mice on the immune-mediated disorders, mice injected with concanavalin A (ConA) were cohoused with healthy or sick mice or with steroid-treated or untreated mice. To determine the effect of cohousing on acetaminophen (APAP)-induced liver damage, APAP-injected mice were cohoused with N-acetyl-cysteine (NAC)-treated or untreated mice. In the ConA-induced immune-mediated hepatitis model, cohousing of sick with healthy mice was associated with the alleviation of liver damage in sick animals. Similarly, a significant decrease in serum ALT was noted in ConA-injected mice kept in the same cage as ConAinjected mice treated with steroids. A trend for reduction in liver enzymes in APAPinjected mice was observed upon cohousing with NAC-treated animals. Cohousing of sick mice with healthy or treated mice ameliorated the immune-mediated inflam-
Abstract—
1
Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Ein-Kerem, POB 1200, IL91120 Jerusalem, Israel 2 To whom correspondence should be addressed at Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Ein-Kerem, POB 1200, IL91120 Jerusalem, Israel. Email: [email protected] Abbreviations ConA, Concanavalin A; NAC, N-Acetyl-cysteine; APAP, Acetaminophen; IBD, Inflammatory bowel disease; TLR, Toll-like receptor; TNF-α, Tumor necrosis factor-alpha; NAFLD, Nonalcoholic fatty liver disease; NASH, Nonalcoholic steatohepatitis; NLRP, Nod-like receptor protein; IFNAR1, Type I interferon receptor; TMF/ARA160, TATA element modulatory factor
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Shabat, Lichtenstein, and Ilan matory state induced by ConA and APAP. These models for liver damage can serve as biological systems for determining the effects of alterations in the ecosystem on the immune system. KEY WORDS: ConA hepatitis; Cohousing; Coprophagy.
INTRODUCTION Cohousing of sick with healthy or treated animals is based on the concept of sharing an intestinal ecosystem and coprophagy, the consumption of feces, which may include active drug metabolites secreted in the feces or urine [1]. Marking laboratory mice so that they can be individually identified is the current practice in many labs. The influences that mixed strain housing exerts on the phenotypes of mice and on the
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