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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 EE and IE in combination with abstinence on the recovery from ketamine-induced renal toxicity.(A) The kidney and body weight ratio of the Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (B–E). Representative images of H&E staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents tubular edema. (F) KIM-1 levels of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (G–J). Representive images of IHC staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents a cell with positive expression of KIM-1. (K) KIM-1 levels of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups. (I) TUNEL + cells (%) of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (L, M, N, O) Representive images of TUNEL staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents an apoptotic cell. Data are expressed as mean ± SEM. KIM-1: Kidney Injury Molecule 1; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining; IE: isolated environment; EE: enriched environment; KW: kidney weight; BW: body weight.
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f7: Effects of EE and IE in combination with abstinence on the recovery from ketamine-induced renal toxicity.(A) The kidney and body weight ratio of the Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (B–E). Representative images of H&E staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents tubular edema. (F) KIM-1 levels of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (G–J). Representive images of IHC staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents a cell with positive expression of KIM-1. (K) KIM-1 levels of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups. (I) TUNEL + cells (%) of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (L, M, N, O) Representive images of TUNEL staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents an apoptotic cell. Data are expressed as mean ± SEM. KIM-1: Kidney Injury Molecule 1; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining; IE: isolated environment; EE: enriched environment; KW: kidney weight; BW: body weight.

Mentions: A two-way ANOVA major effect of Drug (saline vs. ketamine) was found in both HW/BW (F(1,23) = 123.139, p < 0.01) and KW/BW (F(1,23) = 209.747, p < 0.01) ratio. The effect of Condition (IE vs. EE) was significant in the HW/BW ratio ((F(1,23) = 5.471, p = 0.029), but not in the KW/BW ratio (F(1,23) = 1.569, p = 0.224); Fig. 6A and 7A; Table 2). Post-hoc tests revealed that both the Ketamine SA + IE and Ketamine SA + EE group exhibited a significantly higher HW/BW ratio than their corresponding control group (Ketamine SA + IE: p < 0.01; Ketamine SA + EE: p < 0.01; Fig. 6B–E). There was also a significant difference in HW/BW and KW/BW between Ketamine SA + IE and Ketamine SA + EE group (HW/BW: p = 0.051; KW/BW: p = 0.046; Fig. 6C,E and 7C,E). For the level FAS, the was a significant effect of Drug (F(1,51) = 25.437, p < 0.01), but not Condition (F(1,51) = 2.030, p = 0.161). For the level of KIM-1, there was a significant effect of both Drug and Condition (Drug: F(1,51) = 78.337, p < 0.01; Condition: F(1,51) = 15.792, p < 0.01; Fig. 6F and 7F; Table 2). Post-hoc tests showed that the EE condition significantly decreased the level of FAS and KIM-1, compared with the IE condition (FAS: p = 0.045; KIM-1: p < 0.01; Fig. 6H,J and Fig. 7H,J). However, animals undergoing either the EE or IE abstinence still exhibited a significantly higher level of FAS and KIM-1 than their corresponding control ones (p < 0.01). The degree of apoptosis in the heart and kidney was also significantly different for the factor of Drug and Condition (Heart/Drug: F(1, 47) = 49.202, p < 0.01; Heart/Condition: F(1, 47) = 25.103, p < 0.01; Kidney/Drug: F(1, 47) = 8.400, p = 0.006; Kidney/Condition: F(1, 47) = 9.449, p = 0.004; Fig. 6K and 7K; Table 2). Similarly, the apoptotic level of the heart and kidney was significantly decreased by EE abstinence, relative to IE abstinence (p < 0.01). However, either EE or IE abstinence group exerted a significant increase in apoptosis of the heart and kidney, compared with their corresponding control group (p < 0.01).


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 EE and IE in combination with abstinence on the recovery from ketamine-induced renal toxicity.(A) The kidney and body weight ratio of the Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (B–E). Representative images of H&E staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents tubular edema. (F) KIM-1 levels of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (G–J). Representive images of IHC staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents a cell with positive expression of KIM-1. (K) KIM-1 levels of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups. (I) TUNEL + cells (%) of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (L, M, N, O) Representive images of TUNEL staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents an apoptotic cell. Data are expressed as mean ± SEM. KIM-1: Kidney Injury Molecule 1; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining; IE: isolated environment; EE: enriched environment; KW: kidney weight; BW: body weight.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Effects of EE and IE in combination with abstinence on the recovery from ketamine-induced renal toxicity.(A) The kidney and body weight ratio of the Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (B–E). Representative images of H&E staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents tubular edema. (F) KIM-1 levels of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (G–J). Representive images of IHC staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents a cell with positive expression of KIM-1. (K) KIM-1 levels of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups. (I) TUNEL + cells (%) of Ketamine SA + IE, Ketamine SA + EE groups and the corresponding control (Saline + IE, Saline + EE) groups (L, M, N, O) Representive images of TUNEL staining for a Saline + IE, a Ketamine SA + IE, a Saline + EE, and a Ketamine SA + EE rat. Arrow represents an apoptotic cell. Data are expressed as mean ± SEM. KIM-1: Kidney Injury Molecule 1; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining; IE: isolated environment; EE: enriched environment; KW: kidney weight; BW: body weight.
Mentions: A two-way ANOVA major effect of Drug (saline vs. ketamine) was found in both HW/BW (F(1,23) = 123.139, p < 0.01) and KW/BW (F(1,23) = 209.747, p < 0.01) ratio. The effect of Condition (IE vs. EE) was significant in the HW/BW ratio ((F(1,23) = 5.471, p = 0.029), but not in the KW/BW ratio (F(1,23) = 1.569, p = 0.224); Fig. 6A and 7A; Table 2). Post-hoc tests revealed that both the Ketamine SA + IE and Ketamine SA + EE group exhibited a significantly higher HW/BW ratio than their corresponding control group (Ketamine SA + IE: p < 0.01; Ketamine SA + EE: p < 0.01; Fig. 6B–E). There was also a significant difference in HW/BW and KW/BW between Ketamine SA + IE and Ketamine SA + EE group (HW/BW: p = 0.051; KW/BW: p = 0.046; Fig. 6C,E and 7C,E). For the level FAS, the was a significant effect of Drug (F(1,51) = 25.437, p < 0.01), but not Condition (F(1,51) = 2.030, p = 0.161). For the level of KIM-1, there was a significant effect of both Drug and Condition (Drug: F(1,51) = 78.337, p < 0.01; Condition: F(1,51) = 15.792, p < 0.01; Fig. 6F and 7F; Table 2). Post-hoc tests showed that the EE condition significantly decreased the level of FAS and KIM-1, compared with the IE condition (FAS: p = 0.045; KIM-1: p < 0.01; Fig. 6H,J and Fig. 7H,J). However, animals undergoing either the EE or IE abstinence still exhibited a significantly higher level of FAS and KIM-1 than their corresponding control ones (p < 0.01). The degree of apoptosis in the heart and kidney was also significantly different for the factor of Drug and Condition (Heart/Drug: F(1, 47) = 49.202, p < 0.01; Heart/Condition: F(1, 47) = 25.103, p < 0.01; Kidney/Drug: F(1, 47) = 8.400, p = 0.006; Kidney/Condition: F(1, 47) = 9.449, p = 0.004; Fig. 6K and 7K; Table 2). Similarly, the apoptotic level of the heart and kidney was significantly decreased by EE abstinence, relative to IE abstinence (p < 0.01). However, either EE or IE abstinence group exerted a significant increase in apoptosis of the heart and kidney, compared with their corresponding control group (p < 0.01).

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