Methylglyoxal (MG) and Cerebro-Renal Interaction: Does Long-Term Orally Administered MG Cause Cognitive Impairment in Normal Sprague-Dawley Rats?
Abstract
:1. Introduction
2. Results
2.1. Physical Findings and Laboratory Tests
Phase | Age in weeks (W) | MG exposure (W) | Behavior test | Urine & blood test | Mean BP (mmHg) | p Value | Body weight (g) | p Value | ||
---|---|---|---|---|---|---|---|---|---|---|
Control (n = 9) | MG (n = 10) | Control (n = 9) | MG (n = 10) | |||||||
Phase I | 8 | START | - | - | 101 ± 2.1 | 105 ± 2.0 | 0.221 | 281 ± 3.3 | 277 ± 3.8 | 0.527 |
16 | +8 | - | Urine Test (1) | 99.0 ± 4.0 | 99.0 ± 3.3 | 0.935 | 506 ± 10.5 | 487 ± 10.7 | 0.238 | |
16 | +8 | Object exploration Test (1) | - | - | - | - | - | - | - | |
20 ~ 23 | +12~+15 | Radial-arm Maze Test (1) | - | 82.0 ± 2.1 | 79.7 ± 3.4 | 0.594 | 533 ± 10.3 | 509 ± 11.9 | 0.159 | |
Phase II | 31 | +23 | Object exploration Test (2) | - | - | - | - | 569 ± 11.3 | 539 ± 12.8 | 0.116 |
42 ~ 44 | +34~+36 | Radial-arm Maze Test (2) | - | - | - | - | - | - | - | |
45 | +37 | - | Urine Test (2) | - | - | - | - | - | - | |
47 | +39 | (Sacrificed) | Blood Test | 93.4 ± 3.3 | 94.2 ± 4.5 | 0.674 | 603 ± 14.2 | 566 ± 14.5 | 0.083 |
Parameters | Phase I | Phase II | ||||
---|---|---|---|---|---|---|
Control (n = 9) | MG (n = 10) | p Value | Control (n = 9) | MG (n = 10) | p Value | |
Uric Protein (g/gCrea) | 0.7 ± 0.2 | 1.0 ± 0.5 | 0.068 | 3.0 ± 0.7 | 1.8 ± 0.6 | 0.201 |
Urinary 8-OHdG (ng/day) | 252.2 ± 21.1 | 218.9 ± 14.5 | 0.356 | 211.9 ± 12.0 | 205.0 ± 16.3 | 0.549 |
Urinary MDA (nmol/day) | 106.8 ± 9.2 | 101.3 ± 12.6 | 0.733 | 27.0 ± 4.9 | 27.7 ± 4.8 | 0.927 |
BUN (mg/dL) | - | - | - | 20.7 ± 0.6 | 21.9 ± 0.8 | 0.241 |
Serum Creatinine (mg/dL) | - | - | - | 0.30 ± 0.01 | 0.33 ± 0.02 | 0.210 |
Plasma Glucose (mg/dL) | - | - | - | 236.3 ± 7.1 | 221.9 ± 6.4 | 0.149 |
Serum MG (nM) | - | - | - | 244.8 ± 28.2 | 495.8 ± 38.1 | <0.001 |
Plasma MDA (µM) | - | - | - | 0.16 ± 0.04 | 0.14 ± 0.01 | 0.447 |
Plasma AGT (ng/mL) | - | - | - | 3.2 ± 0.3 | 2.1 ± 0.1 | 0.014 |
Urinary AGT (ng/day) | 29.3 ± 6.5 | 16.3 ± 6.3 | 0.034 | |||
Kidney GPx (mU/mg) | - | - | - | 3.6 ± 0.4 | 5.1 ± 0.4 | 0.036 |
Kidney SOD (U/mL/mg) | - | - | - | 3.7 ± 0.9 | 6.3 ± 0.9 | 0.069 |
2.2. Results of Behavioral Testing
2.3. Histological Findings of Brain and Kidney
2.4. Analysis of Oxidative Stress, Antioxidants and Angiotensinogen
3. Discussion
4. Experimental Section
4.1. Animals
4.2. Treatment Protocol
4.3. Behavioral Procedure
4.3.1. Object Exploration Test
4.3.2. Radial Arm Maze Test
4.4. Collection of Blood, Urine, Kidney and Brain Samples
4.5. Sample Analysis
4.6. Statistical Analysis
5. Conclusions
Acknowledgments
Conflicts of Interest
References
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Watanabe, K.; Okada, K.; Fukabori, R.; Hayashi, Y.; Asahi, K.; Terawaki, H.; Kobayashi, K.; Watanabe, T.; Nakayama, M. Methylglyoxal (MG) and Cerebro-Renal Interaction: Does Long-Term Orally Administered MG Cause Cognitive Impairment in Normal Sprague-Dawley Rats? Toxins 2014, 6, 254-269. https://doi.org/10.3390/toxins6010254
Watanabe K, Okada K, Fukabori R, Hayashi Y, Asahi K, Terawaki H, Kobayashi K, Watanabe T, Nakayama M. Methylglyoxal (MG) and Cerebro-Renal Interaction: Does Long-Term Orally Administered MG Cause Cognitive Impairment in Normal Sprague-Dawley Rats? Toxins. 2014; 6(1):254-269. https://doi.org/10.3390/toxins6010254
Chicago/Turabian StyleWatanabe, Kimio, Kana Okada, Ryoji Fukabori, Yoshimitsu Hayashi, Koichi Asahi, Hiroyuki Terawaki, Kazuto Kobayashi, Tsuyoshi Watanabe, and Masaaki Nakayama. 2014. "Methylglyoxal (MG) and Cerebro-Renal Interaction: Does Long-Term Orally Administered MG Cause Cognitive Impairment in Normal Sprague-Dawley Rats?" Toxins 6, no. 1: 254-269. https://doi.org/10.3390/toxins6010254