Caffeine improves bladder function in diabetic rats via a neuroprotective effect

Xue,Jun; Liu,Yadong; Zhang,Sichong; Ding,Liucheng; Shen,Baixin; Shao,Yunpeng; Wei,Zhongqing

doi:10.3892/etm.2021.9932

Caffeine improves bladder function in diabetic rats via a neuroprotective effect

Authors:
- Jun Xue
- Yadong Liu
- Sichong Zhang
- Liucheng Ding
- Baixin Shen
- Yunpeng Shao
- Zhongqing Wei
View Affiliations

Affiliations: Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China
Published online on: March 17, 2021 https://doi.org/10.3892/etm.2021.9932
Article Number: 501
Copyright: © Xue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Diabetic cystopathy (DCP) is one of the most common complications of diabetes mellitus (DM). A previous study reported that caffeine may improve bladder dysfunction in rats with DM. The aim of the present study was to investigate the mechanisms behind the capacity for caffeine to improve bladder function in rats with DM. Sprague Dawley rats were divided into four groups: control, caffeine, DM and DM plus caffeine treatment (DM + caffeine). Bladder function was measured by urodynamic analyses. The levels of nerve growth factor (NGF), brain‑derived neurotrophic factor (BDNF) and calcitonin gene‑related peptide (CGRP) in the bladder tissue were detected by ELISA. Apoptosis in the dorsal root ganglion (DRG) was detected by terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling assay. The expression levels of B‑cell lymphoma‑2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), caspase‑3, cleaved caspase‑3, caspase‑9 and cleaved caspase‑9 proteins in the DRG were detected by western blotting. Following treatment with caffeine, the urination time and micturition interval of rats with DM were improved, the bladder wet weight was decreased, and the maximum voiding pressure was increased. Relative to that in the DM group, the expression levels of NGF, BDNF and CGRP in the bladder tissue of DM + caffeine rats increased; cellular apoptosis in the DRG of DM + caffeine rates decreased; and the expression levels of Bcl‑2, Bax, cleaved caspase‑3 and cleaved caspase‑9 proteins in the DRG of DM + caffeine rats were restored to a certain extent. In conclusion, caffeine promotes bladder function in rats with DM through a protective effect on DRG.

View Figures

View References

1	Xu Y, Wang L, He J, Bi Y, Li M, Wang T, Wang L, Jiang Y, Dai M, Lu J, et al: Prevalence and control of diabetes in Chinese adults. JAMA. 310:948–959. 2013.PubMed/NCBI View Article : Google Scholar
2	Yuan Z, Tang Z, He C and Tang W: Diabetic cystopathy: A review. J Diabetes. 7:442–447. 2015.PubMed/NCBI View Article : Google Scholar
3	Arrellano-Valdez F, Urrutia-Osorio M, Arroyo C and Soto-Vega E: A comprehensive review of urologic complications in patients with diabetes. Springerplus. 3(549)2014.PubMed/NCBI View Article : Google Scholar
4	Feifer A and Corcos J: Contemporary role of suprapubic cystostomy in treatment of neuropathic bladder dysfunction in spinal cord injured patients. Neurourol Urodyn. 27:475–479. 2008.PubMed/NCBI View Article : Google Scholar
5	Franz MJ, Bantle JP, Beebe CA, Brunzell JD, Chiasson JL, Garg A, Holzmeister LA, Hoogwerf B, Mayer-Davis E, Mooradian AD, et al: Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care. 26 (Suppl 1):S51–S61. 2003.PubMed/NCBI View Article : Google Scholar
6	Cho YS, Ko IG, Kim SE, Hwan L, Shin MS, Kim CJ, Kim SH, Jin JJ, Chung JY and Kim KH: Caffeine enhances micturition through neuronal activation in micturition centers. Mol Med Rep. 10:2931–2936. 2014.PubMed/NCBI View Article : Google Scholar
7	Yi CR, Wei ZQ, Deng XL, Sun ZY, Li XR and Tian CG: Effects of coffee and caffeine on bladder dysfunction in streptozotocin-induced diabetic rats. Acta Pharmacol Sin. 27:1037–1043. 2006.PubMed/NCBI View Article : Google Scholar
8	Langdale CL, Thor KB, Marson L and Burgard EC: Maintenance of bladder innervation in diabetes: A stereological study of streptozotocin-treated female rats. Auton Neurosci. 185:59–66. 2014.PubMed/NCBI View Article : Google Scholar
9	WenBo W, Fei Z, YiHeng D, Wei W, TingMang Y, WenHao Z, QianRu L and HaiTao L: Human umbilical cord mesenchymal stem cells overexpressing nerve growth factor ameliorate diabetic cystopathy in rats. Neurochem Res. 42:3537–3547. 2017.PubMed/NCBI View Article : Google Scholar
10	Liu YD, Zhang SC, Xue J, Wei ZQ, Shen BX and Ding LC: Caffeine improves bladder function in streptozotocin-induced diabetic rats. Neurourol Urodyn. 38:81–86. 2018.PubMed/NCBI View Article : Google Scholar
11	Kashyap M, Pore S, Yoshimura N and Tyagi P: Constitutive expression Of NGF, P75(NTR) affected by bladder distension and NGF antisense treatment. Life Sci. 148:93–98. 2016.PubMed/NCBI View Article : Google Scholar
12	Wada N, Shimizu T, Shimizu N, de Groat WC, Kanai AJ, Tyagi P, Kakizaki H and Yoshimura N: The effect of neutralization of nerve growth factor (NGF) on bladder and urethral dysfunction in mice with spinal cord injury. Neurourol Urodyn. 37:1889–1896. 2018.PubMed/NCBI View Article : Google Scholar
13	Tonyali S, Ates D, Akbiyik F, Kankaya D, Baydar D and Ergen A: Urine nerve growth factor (NGF) level, bladder nerve staining and symptom/problem scores in patients with interstitial cystitis. Adv Clin Exp Med. 27:159–163. 2018.PubMed/NCBI View Article : Google Scholar
14	Kashyap MP, Pore SK, de Groat WC, Chermansky CJ, Yoshimura N and Tyagi P: BDNF overexpression in the bladder induces neuronal changes to mediate bladder overactivity. Am J Physiol Renal Physiol. 315:F45–F56. 2018.PubMed/NCBI View Article : Google Scholar
15	Kashyap MP, Roberts C, Waseem M and Tyagi P: Drug targets in neurotrophin signaling in the central and peripheral nervous system. Mol Neurobiol. 55:6939–6955. 2018.PubMed/NCBI View Article : Google Scholar
16	Parameswaran N, Disa J, Spielman WS, Brooks DP, Nambi P and Aiyar N: Activation of multiple mitogen-activated protein kinases by recombinant calcitonin gene-related peptide receptor. Eur J Pharmacol. 389:125–130. 2000.PubMed/NCBI View Article : Google Scholar
17	Nirmal J, Tyagi P, Chuang YC, Lee WC, Yoshimura N, Huang CC, Rajaganapathy B and Chancellor MB: Functional and molecular characterization of hyposensitive underactive bladder tissue and urine in streptozotocin-induced diabetic rat. PLoS One. 9(e102644)2014.PubMed/NCBI View Article : Google Scholar
18	Daneshgari F, Liu G, Birder L, Hanna-Mitchell AT and Chacko S: Diabetic bladder dysfunction: Current translational knowledge. J Urol. 182 (Suppl 6):S18–S26. 2009.PubMed/NCBI View Article : Google Scholar
19	Li R, Wu Y, Zou S, Wang X, Li Y, Xu K, Gong F, Liu Y, Wang J, Liao Y, et al: NGF attenuates high glucose-induced ER stress, preventing schwann cell apoptosis by activating the PI3K/Akt/GSK3β and ERK1/2 pathways. Neurochem Res. 42:3005–3018. 2017.PubMed/NCBI View Article : Google Scholar
20	Sun Z, Hu W, Yin S, Lu X, Zuo W, Ge S and Xu Y: NGF protects against oxygen and glucose deprivation-induced oxidative stress and apoptosis by up-regulation of HO-1 through MEK/ERK pathway. Neurosci Lett. 641:8–14. 2017.PubMed/NCBI View Article : Google Scholar
21	Cao J, Wu Y, Liu G and Li Z: Over-expression of BDNF inhibits angiotensin II-induced apoptosis of cardiomyocytes in SD rats. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 34:218–224. 2018.PubMed/NCBI(In Chinese).
22	Qi G, Mi Y, Wang Y, Li R, Huang S, Li X and Liu X: Neuroprotective action of tea polyphenols on oxidative stress-induced apoptosis through the activation of the TrkB/CREB/BDNF pathway and Keap1/Nrf2 signaling pathway in SH-SY5Y cells and mice brain. Food Funct. 8:4421–4432. 2017.PubMed/NCBI View Article : Google Scholar
23	Ma YX, Guo Z and Sun T: CGRP inhibits norepinephrine induced apoptosis with restoration of Bcl-2/Bax in cultured cardiomyocytes of rat. Neurosci Lett. 549:130–134. 2013.PubMed/NCBI View Article : Google Scholar
24	Yang JH, Zhang YQ and Guo Z: Endogenous CGRP protects retinal cells against stress induced apoptosis in rats. Neurosci Lett. 501:83–85. 2011.PubMed/NCBI View Article : Google Scholar
25	Renault TT, Dejean LM and Manon S: A brewing understanding of the regulation of Bax function by Bcl-xL and Bcl-2. Mech Ageing Dev. 161:201–210. 2017.PubMed/NCBI View Article : Google Scholar
26	Vogel MW: Cell death, Bcl-2, Bax, and the cerebellum. Cerebellum. 1:277–287. 2002.PubMed/NCBI View Article : Google Scholar
27	Song L, Gao LN, Wang J, Thapa S, Li Y, Zhong XB, Zhao HW, Xiang XR, Zhang FG and Ji P: Stromal cell-derived factor-1α alleviates calcium-sensing receptor activation-mediated ischemia/reperfusion injury by inhibiting caspase-3/caspase-9-induced cell apoptosis in rat free flaps. Biomed Res Int. 2018(8945850)2018.PubMed/NCBI View Article : Google Scholar
28	Lan T, Zhao H, Xiang B, Wang J and Liu Y: Suture compression induced midpalatal suture chondrocyte apoptosis with increased caspase-3, caspase-9, Bad, Bak, Bax and Bid expression. Biochem Biophys Res Commun. 489:179–186. 2017.PubMed/NCBI View Article : Google Scholar