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Environmental enrichment and abstinence attenuate ketamine-induced cardiac and renal toxicity.

Li X, Li S, Zheng W, Pan J, Huang K, Chen R, Pan T, Liao G, Chen Z, Zhou D, Shen W, Zhou W, Liu Y - Sci Rep (2015)

Bottom Line: Two weeks of ketamine SA caused significant increases in organ weight, Apoptosis Stimulating Fragment/Kidney Injury Molecule-1, and apoptotic level of heart and kidney.The extended length of withdrawal from ketamine SA partially reduced toxicity on the heart and kidney.The interactive effect of EE and abstinence was promising to promote the recovery of cardiac and renal toxicity of ketamine.

View Article: PubMed Central - PubMed

Affiliation: Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, P. R. China.

ABSTRACT
The current study was designed to investigate the effect of abstinence in combination with environmental enrichment (EE) on cardiac and renal toxicity induced by 2 weeks of ketamine self-administration (SA) in rodents. In Experiment 1, one group of rats underwent ketamine SA for 14 days. In Experiment 2, the animals completed 2 weeks of ketamine SA followed by 2 and 4 weeks of abstinence. In Experiment 3, animals underwent 14 days of ketamine SA and 4 weeks of abstinence in which isolated environment (IE) and EE was introduced. The corresponding control groups were included for each experiment. Two weeks of ketamine SA caused significant increases in organ weight, Apoptosis Stimulating Fragment/Kidney Injury Molecule-1, and apoptotic level of heart and kidney. The extended length of withdrawal from ketamine SA partially reduced toxicity on the heart and kidney. Finally, introduction of EE during the period of abstinence greatly promoted the effect of abstinence on ketamine-induced cardiac and renal toxicity. The interactive effect of EE and abstinence was promising to promote the recovery of cardiac and renal toxicity of ketamine.

No MeSH data available.


Related in: MedlinePlus

The effects of ketamine SA on morphological alterations and toxicity of the heart.(A,B) Representative images of H&E staining for a Saline and a Ketamine SA rat. Arrow represents the irregular arrangement of myocardial cells (C,D) Representative images of IHC staining for a saline and a ketamine SA rat. Arrow represents a cell with positive expression of FAS. (E) The level of FAS for the saline (left) and the Ketamine SA (right) groups. (F,G) Representative TUNEL staining images for a saline and a ketamine SA rat. Arrow represents an apoptotic cell. (H) TUNEL + cells (%) for saline (left) and ketamine SA (right) groups. Data are expressed as mean ± SEM. ** p < 0.01 FAS: apoptosis stimulating fragment; SA: self-administration; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. The FAS level was defined as the average integral optical density.
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f2: The effects of ketamine SA on morphological alterations and toxicity of the heart.(A,B) Representative images of H&E staining for a Saline and a Ketamine SA rat. Arrow represents the irregular arrangement of myocardial cells (C,D) Representative images of IHC staining for a saline and a ketamine SA rat. Arrow represents a cell with positive expression of FAS. (E) The level of FAS for the saline (left) and the Ketamine SA (right) groups. (F,G) Representative TUNEL staining images for a saline and a ketamine SA rat. Arrow represents an apoptotic cell. (H) TUNEL + cells (%) for saline (left) and ketamine SA (right) groups. Data are expressed as mean ± SEM. ** p < 0.01 FAS: apoptosis stimulating fragment; SA: self-administration; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. The FAS level was defined as the average integral optical density.

Mentions: Independent t-test revealed that both the heart weight/body ratio (HW/BW) and kidney weight/body weight ratio (KW/BW) were significantly higher in the Ketamine SA group than in the corresponding control group (HW/BW: p = 0.009; KW/BW: p < 0.01; Fig. 1C,D). Ketamine SA produced toxicity on the heart. The H&E staining results revealed that normal myocardial cells were arranged regularly (Fig. 2A). In contrast, myocardial cells were arranged irregularly and the nuclei seemed to be distorted and varied in size in the Ketamine SA group (Fig. 2B). Moreover, ketamine SA significantly increased the level of apoptosis stimulating fragment (FAS) level determined by optical density, compared with the corresponding control group (p < 0.01; Fig. 2C–E). Finally, TUNEL staining results indicated that the percentage of apoptotic cell number per unit area in the heart was significantly higher in the Ketamine SA group than that in the corresponding control group (p < 0.01; Fig. 2F–H).


Environmental enrichment and abstinence attenuate ketamine-induced cardiac and renal toxicity.

Li X, Li S, Zheng W, Pan J, Huang K, Chen R, Pan T, Liao G, Chen Z, Zhou D, Shen W, Zhou W, Liu Y - Sci Rep (2015)

The effects of ketamine SA on morphological alterations and toxicity of the heart.(A,B) Representative images of H&E staining for a Saline and a Ketamine SA rat. Arrow represents the irregular arrangement of myocardial cells (C,D) Representative images of IHC staining for a saline and a ketamine SA rat. Arrow represents a cell with positive expression of FAS. (E) The level of FAS for the saline (left) and the Ketamine SA (right) groups. (F,G) Representative TUNEL staining images for a saline and a ketamine SA rat. Arrow represents an apoptotic cell. (H) TUNEL + cells (%) for saline (left) and ketamine SA (right) groups. Data are expressed as mean ± SEM. ** p < 0.01 FAS: apoptosis stimulating fragment; SA: self-administration; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. The FAS level was defined as the average integral optical density.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4481381&req=5

f2: The effects of ketamine SA on morphological alterations and toxicity of the heart.(A,B) Representative images of H&E staining for a Saline and a Ketamine SA rat. Arrow represents the irregular arrangement of myocardial cells (C,D) Representative images of IHC staining for a saline and a ketamine SA rat. Arrow represents a cell with positive expression of FAS. (E) The level of FAS for the saline (left) and the Ketamine SA (right) groups. (F,G) Representative TUNEL staining images for a saline and a ketamine SA rat. Arrow represents an apoptotic cell. (H) TUNEL + cells (%) for saline (left) and ketamine SA (right) groups. Data are expressed as mean ± SEM. ** p < 0.01 FAS: apoptosis stimulating fragment; SA: self-administration; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. The FAS level was defined as the average integral optical density.
Mentions: Independent t-test revealed that both the heart weight/body ratio (HW/BW) and kidney weight/body weight ratio (KW/BW) were significantly higher in the Ketamine SA group than in the corresponding control group (HW/BW: p = 0.009; KW/BW: p < 0.01; Fig. 1C,D). Ketamine SA produced toxicity on the heart. The H&E staining results revealed that normal myocardial cells were arranged regularly (Fig. 2A). In contrast, myocardial cells were arranged irregularly and the nuclei seemed to be distorted and varied in size in the Ketamine SA group (Fig. 2B). Moreover, ketamine SA significantly increased the level of apoptosis stimulating fragment (FAS) level determined by optical density, compared with the corresponding control group (p < 0.01; Fig. 2C–E). Finally, TUNEL staining results indicated that the percentage of apoptotic cell number per unit area in the heart was significantly higher in the Ketamine SA group than that in the corresponding control group (p < 0.01; Fig. 2F–H).

Bottom Line: Two weeks of ketamine SA caused significant increases in organ weight, Apoptosis Stimulating Fragment/Kidney Injury Molecule-1, and apoptotic level of heart and kidney.The extended length of withdrawal from ketamine SA partially reduced toxicity on the heart and kidney.The interactive effect of EE and abstinence was promising to promote the recovery of cardiac and renal toxicity of ketamine.

View Article: PubMed Central - PubMed

Affiliation: Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang 315211, P. R. China.

ABSTRACT
The current study was designed to investigate the effect of abstinence in combination with environmental enrichment (EE) on cardiac and renal toxicity induced by 2 weeks of ketamine self-administration (SA) in rodents. In Experiment 1, one group of rats underwent ketamine SA for 14 days. In Experiment 2, the animals completed 2 weeks of ketamine SA followed by 2 and 4 weeks of abstinence. In Experiment 3, animals underwent 14 days of ketamine SA and 4 weeks of abstinence in which isolated environment (IE) and EE was introduced. The corresponding control groups were included for each experiment. Two weeks of ketamine SA caused significant increases in organ weight, Apoptosis Stimulating Fragment/Kidney Injury Molecule-1, and apoptotic level of heart and kidney. The extended length of withdrawal from ketamine SA partially reduced toxicity on the heart and kidney. Finally, introduction of EE during the period of abstinence greatly promoted the effect of abstinence on ketamine-induced cardiac and renal toxicity. The interactive effect of EE and abstinence was promising to promote the recovery of cardiac and renal toxicity of ketamine.

No MeSH data available.


Related in: MedlinePlus