open access
Curcumin reduces blood-nerve barrier abnormalities and cytotoxicity to endothelial cells and pericytes induced by cisplatin
, 1, 1, 1, 1
Affiliations- Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
open access
Abstract
Background: Cisplatin is a platinum-based antineoplastic agent used to treat
cancers of solid organs. Neuropathy is one of its major side effects, necessitating
dose reduction or cessation. Previous studies suggested that cisplatin causes
microvascular toxicity, including pericyte detachment. This study aimed to clarify
whether these alterations occurred in the blood–nerve barrier (BNB) of capillaries
after cisplatin treatment.
Materials and methods and Results: Electron microscopic analysis of rat sciatic
nerves with cisplatin neuropathy showed increased frequency and severity of
pericyte detachment. Moreover, the vascular basement membrane did not tightly
encircle around the endothelial cells and pericytes. Cultured human umbilical vein
endothelial cells and human brain vascular pericytes showed reduced viability,
increased caspase-3 activity and enhanced oxidative stress following cisplatin
treatment. In addition, cisplatin decreased transendothelial electrical resistance
(TEER) and the expression of the tight junction proteins occludin and zonula
occludens-1. Curcumin, a polyphenol found in the root of Curcuma longa, had
favourable effects on cisplatin neuropathy in previous work. Therefore, curcumin
was tested to determine whether it had any effect on these abnormalities. Curcumin
alleviated pericyte detachment, cytotoxicity, oxidative stress, TEER reduction
and tight junction protein expression.
Conclusions: These data indicate that cisplatin causes BNB disruption in the
nerves and might result in neuropathy. Curcumin might improve neuropathy via
the restoration of BNB. Whether alterations in the BNB occur and curcumin is
effective in patients with cisplatin neuropathy remain to be investigated.
Abstract
Background: Cisplatin is a platinum-based antineoplastic agent used to treat
cancers of solid organs. Neuropathy is one of its major side effects, necessitating
dose reduction or cessation. Previous studies suggested that cisplatin causes
microvascular toxicity, including pericyte detachment. This study aimed to clarify
whether these alterations occurred in the blood–nerve barrier (BNB) of capillaries
after cisplatin treatment.
Materials and methods and Results: Electron microscopic analysis of rat sciatic
nerves with cisplatin neuropathy showed increased frequency and severity of
pericyte detachment. Moreover, the vascular basement membrane did not tightly
encircle around the endothelial cells and pericytes. Cultured human umbilical vein
endothelial cells and human brain vascular pericytes showed reduced viability,
increased caspase-3 activity and enhanced oxidative stress following cisplatin
treatment. In addition, cisplatin decreased transendothelial electrical resistance
(TEER) and the expression of the tight junction proteins occludin and zonula
occludens-1. Curcumin, a polyphenol found in the root of Curcuma longa, had
favourable effects on cisplatin neuropathy in previous work. Therefore, curcumin
was tested to determine whether it had any effect on these abnormalities. Curcumin
alleviated pericyte detachment, cytotoxicity, oxidative stress, TEER reduction
and tight junction protein expression.
Conclusions: These data indicate that cisplatin causes BNB disruption in the
nerves and might result in neuropathy. Curcumin might improve neuropathy via
the restoration of BNB. Whether alterations in the BNB occur and curcumin is
effective in patients with cisplatin neuropathy remain to be investigated.
Keywords
capillaries, cisplatin, nerve, neuropathy
About this articleTitle
Curcumin reduces blood-nerve barrier abnormalities and cytotoxicity to endothelial cells and pericytes induced by cisplatin
Journal
Issue
Article type
Original article
Pages
533-542
Published online
2022-07-08
Page views
1324
Article views/downloads
944
DOI
Pubmed
Bibliographic record
Folia Morphol 2023;82(3):533-542.
Keywords
capillaries
cisplatin
nerve
neuropathy
Authors
P. Kobutree
A. Tothonglor
A. Roumwong
D. Jindatip
S. Agthong
References (38)- Abadi AJ, Mirzaei S, Mahabady MK, et al. Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects. Phytother Res. 2022; 36(1): 189–213.
- Agthong S, Kaewsema A, Charoensub T. Curcumin ameliorates functional and structural abnormalities in cisplatin-induced neuropathy. Exp Neurobiol. 2015; 24(2): 139–145.
- Al Moundhri MS, Al-Salam S, Al Mahrouqee A, et al. The effect of curcumin on oxaliplatin and cisplatin neurotoxicity in rats: some behavioral, biochemical, and histopathological studies. J Med Toxicol. 2013; 9(1): 25–33.
- Anand P, Kunnumakkara AB, Newman RA, et al. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007; 4(6): 807–818.
- Authier N, Gillet JP, Fialip J, et al. An animal model of nociceptive peripheral neuropathy following repeated cisplatin injections. Exp Neurol. 2003; 182(1): 12–20.
- Basu P, Maier C, Basu A. Effects of curcumin and its different formulations in preclinical and clinical studies of peripheral neuropathic and postoperative pain: a comprehensive review. Int J Mol Sci. 2021; 22(9): 4666.
- Branca JJ, Maresca M, Morucci G, et al. Oxaliplatin-induced blood brain barrier loosening: a new point of view on chemotherapy-induced neurotoxicity. Oncotarget. 2018; 9(34): 23426–23438.
- Cole GM, Teter B, Frautschy SA. Neuroprotective effects of curcumin. Adv Exp Med Biol. 2007; 595: 197–212.
- Dieckmann KP, Struss WJ, Budde U. Evidence for acute vascular toxicity of cisplatin-based chemotherapy in patients with germ cell tumour. Anticancer Res. 2011; 31(12): 4501–4505.
- Dilruba S, Kalayda GV. Platinum-based drugs: past, present and future. Cancer Chemother Pharmacol. 2016; 77(6): 1103–1124.
- Dore-Duffy P, Owen C, Balabanov R, et al. Pericyte migration from the vascular wall in response to traumatic brain injury. Microvasc Res. 2000; 60(1): 55–69.
- Dursun B, He Z, Somerset H, et al. Caspases and calpain are independent mediators of cisplatin-induced endothelial cell necrosis. Am J Physiol Renal Physiol. 2006; 291(3): F578–F587.
- Eguchi R, Fujimori Y, Ohta T, et al. Calpain is involved in cisplatin-induced endothelial injury in an in vitro three-dimensional blood vessel model. Int J Oncol. 2010; 37(5): 1289–1296.
- Epstein J, Sanderson IR, Macdonald TT. Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies. Br J Nutr. 2010; 103(11): 1545–1557.
- Hatcher H, Planalp R, Cho J, et al. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci. 2008; 65(11): 1631–1652.
- Jindatip D, Fujiwara K, Sarachana T, et al. Characteristics of pericytes in diethylstilbestrol (DES)-induced pituitary prolactinoma in rats. Med Mol Morphol. 2018; 51(3): 147–155.
- Jindatip D, Nopparat W, Kobutree P, et al. Pericyte loss and detachment in experimental cisplatin-induced neuropathy. Int J Morphol. 2019; 37(2): 509–514.
- Kirchmair R, Walter DH, Ii M, et al. Antiangiogenesis mediates cisplatin-induced peripheral neuropathy: attenuation or reversal by local vascular endothelial growth factor gene therapy without augmenting tumor growth. Circulation. 2005; 111(20): 2662–2670.
- Krarup-Hansen A, Helweg-Larsen S, Schmalbruch H, et al. Neuronal involvement in cisplatin neuropathy: prospective clinical and neurophysiological studies. Brain. 2007; 130(Pt 4): 1076–1088.
- Li SH, Chen WH, Tang Y, et al. Incidence of ischemic stroke post-chemotherapy: a retrospective review of 10,963 patients. Clin Neurol Neurosurg. 2006; 108(2): 150–156.
- Liu YW, Liu CT, Su YL, et al. A narrative review of complementary nutritional supplements for chemotherapy-induced peripheral neuropathy. Altern Ther Health Med. 2020; 26(4): 43–49.
- Maiuolo J, Gliozzi M, Musolino V, et al. The role of endothelial dysfunction in peripheral blood nerve barrier: molecular mechanisms and pathophysiological implications. Int J Mol Sci. 2019; 20(12): 3022.
- Mendonça LM, da Silva Machado C, Teixeira CC, et al. Curcumin reduces cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells. Neurotoxicology. 2013; 34: 205–211.
- Moballegh Nasery M, Abadi B, Poormoghadam D, et al. Curcumin delivery mediated by bio-based nanoparticles: a review. Molecules. 2020; 25(3): 689.
- Notarbartolo M, Poma P, Perri D, et al. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Lett. 2005; 224(1): 53–65.
- Nuver J, De Haas EC, Van Zweeden M, et al. Vascular damage in testicular cancer patients: A study on endothelial activation by bleomycin and cisplatin in vitro. Oncology Reports. 2009; 23(1): 247–253.
- Özkaya D, Nazıroğlu M. Curcumin diminishes cisplatin-induced apoptosis and mitochondrial oxidative stress through inhibition of TRPM2 channel signaling pathway in mouse optic nerve. J Recept Signal Transduct Res. 2020; 40(2): 97–108.
- Peltonen S, Alanne M, Peltonen J. Barriers of the peripheral nerve. Tissue Barriers. 2013; 1(3): e24956.
- Pfister F, Feng Y, vom Hagen F, et al. Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes. 2008; 57(9): 2495–2502.
- Quasthoff S, Hartung HP. Chemotherapy-induced peripheral neuropathy. J Neurol. 2002; 249(1): 9–17.
- Rao R. Oxidative stress-induced disruption of epithelial and endothelial tight junctions. Front Biosci. 2008; 13: 7210–7226.
- Santos NA, Ferreira RS, Santos AC. Overview of cisplatin-induced neurotoxicity and ototoxicity, and the protective agents. Food Chem Toxicol. 2020; 136: 111079.
- Shimizu F, Sano Y, Abe MA, et al. Peripheral nerve pericytes modify the blood-nerve barrier function and tight junctional molecules through the secretion of various soluble factors. J Cell Physiol. 2011; 226(1): 255–266.
- Shimizu F, Sano Y, Haruki H, et al. Advanced glycation end-products induce basement membrane hypertrophy in endoneurial microvessels and disrupt the blood-nerve barrier by stimulating the release of TGF-β and vascular endothelial growth factor (VEGF) by pericytes. Diabetologia. 2011; 54(6): 1517–1526.
- Wongtawatchai T, Agthong S, Kaewsema A, et al. Altered phosphorylation of mitogen-activated protein kinases in dorsal root ganglia and sciatic nerve of rats with cisplatin-induced neuropathy. Asian Biomed (Res Rev News). 2012; 6(3): 397–411.
- Wongtawatchai T, Agthong S, Kaewsema A, et al. Sex-related differences in cisplatin-induced neuropathy in rats. J Med Assoc Thai. 2009; 92(11): 1485–1491.
- Zhang Na, Cai J, Xu L, et al. Cisplatin-Induced stria vascularis damage is associated with inflammation and fibrosis. Neural Plast. 2020; 2020: 8851525.
- Zhang X, Guan Z, Wang X, et al. Curcumin alleviates oxaliplatin-induced peripheral neuropathic pain through inhibiting oxidative stress-mediated activation of NF-κB and mitigating inflammation. Biol Pharm Bull. 2020; 43(2): 348–355.
