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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

Effects of the duration of abstinence on cardiac toxicity induced by ketamine SA.(A) The heart and body weight ratio of Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups (B–G). Representative images of H&E staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents irregular arrangement of myocardial cell. (H) FAS levels of ketamine SA, ketamine SA + 2 W and ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups. (I–N) Representative images of IHC staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents a cell with positive expression of FAS. (O) TUNEL + cells (%) of the Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups (P–U) Representative images of TUNEL staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents an apoptotic cell. Data are expressed as mean ± SEM. FAS: apoptosis stimulating fragment; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining; SA: self-administration; W: week; HW: heart weight; BW: body weight.
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f4: Effects of the duration of abstinence on cardiac toxicity induced by ketamine SA.(A) The heart and body weight ratio of Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups (B–G). Representative images of H&E staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents irregular arrangement of myocardial cell. (H) FAS levels of ketamine SA, ketamine SA + 2 W and ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups. (I–N) Representative images of IHC staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents a cell with positive expression of FAS. (O) TUNEL + cells (%) of the Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups (P–U) Representative images of TUNEL staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents an apoptotic cell. Data are expressed as mean ± SEM. FAS: apoptosis stimulating fragment; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining; SA: self-administration; W: week; HW: heart weight; BW: body weight.

Mentions: A two-way ANOVA analysis revealed that there was a significant Drug (ketamine vs. saline) effect on HW/BW ratio (F(1,41) = 31.855, p < 0.01). The effect of abstinence failed to reach significant (F(2,41) = 3.081, p = 0.06). Post-hoc tests revealed that the HW/BW ratio in the Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups was significantly higher than that of their corresponding control groups (Ketamine SA: p = 0.001; Ketamine SA + 2 W: p = 0.015; Ketamine SA + 4 W: p = 0.003; Fig. 4A; Table 1). The HW/BW ratio for the Ketamine SA group was not significantly different from that for either the Ketamine SA + 2w (p = 0.523) or Ketamine SA + 4 W group (p = 0.095; Fig. 4A; Table 1). Furthermore, a two-way ANOVA revealed a significant drug and abstinence effect on the level of FAS and apoptosis (FAS/Drug: F(1,79) = 287.178 p < 0.01; FAS/Abstinence: F(2, 79) = 20.871, p < 0.01; Apoptosis/Drug: F(1,55) = 163.830, p < 0.01; Apoptosis/Abstinence: F(2,55) = 31.473, p < 0.01; Fig. 4H–U; Table 1). Post hoc tests showed that the Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups showed a significantly higher level of FAS than their corresponding control groups (Ketamine SA: p < 0.01; Ketamine SA + 2 W: p < 0.01; Ketamine SA + 4 W: p < 0.01; Fig. 4I–N; Table 1). The similar pattern was found for the level of apoptosis (Ketamine SA: p < 0.01; Ketamine SA + 2 W: p < 0.01; Ketamine SA + 4 W: p < 0.01; Fig. 4P–U; Table 1).The level of FAS was significantly lowered following 2 and 4 weeks of abstinence, relative to the Ketamine SA group (p < 0.01; Fig. 4J,L,N; Table 1). The similar pattern was also found for the level of apoptosis (p < 0.01; Fig. 4Q,S,U). Additionally, animals in the Ketamine + 4 W group showed a significantly lower level of FAS and apoptosis than those in the Ketamine + 2 W group (p < 0.01; Fig. 4L,N; Fig. 4S,U; Table 1).


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)

Effects of the duration of abstinence on cardiac toxicity induced by ketamine SA.(A) The heart and body weight ratio of Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups (B–G). Representative images of H&E staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents irregular arrangement of myocardial cell. (H) FAS levels of ketamine SA, ketamine SA + 2 W and ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups. (I–N) Representative images of IHC staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents a cell with positive expression of FAS. (O) TUNEL + cells (%) of the Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups (P–U) Representative images of TUNEL staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents an apoptotic cell. Data are expressed as mean ± SEM. FAS: apoptosis stimulating fragment; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining; SA: self-administration; W: week; HW: heart weight; BW: body weight.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Effects of the duration of abstinence on cardiac toxicity induced by ketamine SA.(A) The heart and body weight ratio of Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups (B–G). Representative images of H&E staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents irregular arrangement of myocardial cell. (H) FAS levels of ketamine SA, ketamine SA + 2 W and ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups. (I–N) Representative images of IHC staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents a cell with positive expression of FAS. (O) TUNEL + cells (%) of the Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups and their corresponding control (Saline, Saline + 2 W, Saline + 4 W) groups (P–U) Representative images of TUNEL staining for a Saline, a Ketamine SA, a Saline + 2 W, a Ketamine + 2 W, a Saline + 4 W and a Ketamine SA + 4 W rat. Arrow represents an apoptotic cell. Data are expressed as mean ± SEM. FAS: apoptosis stimulating fragment; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining; SA: self-administration; W: week; HW: heart weight; BW: body weight.
Mentions: A two-way ANOVA analysis revealed that there was a significant Drug (ketamine vs. saline) effect on HW/BW ratio (F(1,41) = 31.855, p < 0.01). The effect of abstinence failed to reach significant (F(2,41) = 3.081, p = 0.06). Post-hoc tests revealed that the HW/BW ratio in the Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups was significantly higher than that of their corresponding control groups (Ketamine SA: p = 0.001; Ketamine SA + 2 W: p = 0.015; Ketamine SA + 4 W: p = 0.003; Fig. 4A; Table 1). The HW/BW ratio for the Ketamine SA group was not significantly different from that for either the Ketamine SA + 2w (p = 0.523) or Ketamine SA + 4 W group (p = 0.095; Fig. 4A; Table 1). Furthermore, a two-way ANOVA revealed a significant drug and abstinence effect on the level of FAS and apoptosis (FAS/Drug: F(1,79) = 287.178 p < 0.01; FAS/Abstinence: F(2, 79) = 20.871, p < 0.01; Apoptosis/Drug: F(1,55) = 163.830, p < 0.01; Apoptosis/Abstinence: F(2,55) = 31.473, p < 0.01; Fig. 4H–U; Table 1). Post hoc tests showed that the Ketamine SA, Ketamine SA + 2 W and Ketamine SA + 4 W groups showed a significantly higher level of FAS than their corresponding control groups (Ketamine SA: p < 0.01; Ketamine SA + 2 W: p < 0.01; Ketamine SA + 4 W: p < 0.01; Fig. 4I–N; Table 1). The similar pattern was found for the level of apoptosis (Ketamine SA: p < 0.01; Ketamine SA + 2 W: p < 0.01; Ketamine SA + 4 W: p < 0.01; Fig. 4P–U; Table 1).The level of FAS was significantly lowered following 2 and 4 weeks of abstinence, relative to the Ketamine SA group (p < 0.01; Fig. 4J,L,N; Table 1). The similar pattern was also found for the level of apoptosis (p < 0.01; Fig. 4Q,S,U). Additionally, animals in the Ketamine + 4 W group showed a significantly lower level of FAS and apoptosis than those in the Ketamine + 2 W group (p < 0.01; Fig. 4L,N; Fig. 4S,U; Table 1).

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