+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

CB1 cannabinoid receptors promote oxidative/nitrosative stress, inflammation and cell death in a murine nephropathy model

CB1 cannabinoid receptors promote oxidative/nitrosative stress, inflammation and cell death in a murine nephropathy model

British Journal of Pharmacology 160(3): 657-668

Accumulating recent evidence suggests that cannabinoid-1 (CB(1)) receptor activation may promote inflammation and cell death and its pharmacological inhibition is associated with anti-inflammatory and tissue-protective effects in various preclinical disease models, as well as in humans. In this study, using molecular biology and biochemistry methods, we have investigated the effects of genetic deletion or pharmacological inhibition of CB(1) receptors on inflammation, oxidative/nitrosative stress and cell death pathways associated with a clinically relevant model of nephropathy, induced by an important chemotherapeutic drug cisplatin. Cisplatin significantly increased endocannabinoid anandamide content, activation of p38 and JNK mitogen-activated protein kinases (MAPKs), apoptotic and poly (ADP-ribose)polymerase-dependent cell death, enhanced inflammation (leucocyte infiltration, tumour necrosis factor-alpha and interleukin-1beta) and promoted oxidative/nitrosative stress [increased expressions of superoxide-generating enzymes (NOX2(gp91phox), NOX4), inducible nitric oxide synthase and tissue 4-hydroxynonenal and nitrotyrosine levels] in the kidneys of mice, accompanied by marked histopathological damage and impaired renal function (elevated creatinine and serum blood urea nitrogen) 3 days following its administration. Both genetic deletion and pharmacological inhibition of CB(1) receptors with AM281 or SR141716 markedly attenuated the cisplatin-induced renal dysfunction and interrelated oxidative/nitrosative stress, p38 and JNK MAPK activation, cell death and inflammatory response in the kidney. The endocannabinoid system through CB(1) receptors promotes cisplatin-induced tissue injury by amplifying MAPK activation, cell death and interrelated inflammation and oxidative/nitrosative stress. These results also suggest that inhibition of CB(1) receptors may exert beneficial effects in renal (and most likely other) diseases associated with enhanced inflammation, oxidative/nitrosative stress and cell death.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 051887028

Download citation: RISBibTeXText

PMID: 20590569

DOI: 10.1111/j.1476-5381.2010.00769.x

Related references

Cannabinoid-2 receptor limits inflammation, oxidative/nitrosative stress, and cell death in nephropathy. Free Radical Biology and Medicine 48(3): 457-467, 2010

CB1 cannabinoid receptors promote oxidative stress and cell death in murine models of doxorubicin-induced cardiomyopathy and in human cardiomyocytes. Cardiovascular Research 85(4): 773-784, 2010

Interplay of oxidative, nitrosative/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy. Biochimica et Biophysica Acta 1852(2): 232-242, 2015

Cannabidiol attenuates cisplatin-induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation, and cell death. Journal of Pharmacology and Experimental Therapeutics 328(3): 708-714, 2009

A new cannabinoid CB2 receptor agonist HU-910 attenuates oxidative stress, inflammation and cell death associated with hepatic ischaemia/reperfusion injury. British Journal of Pharmacology 165(8): 2462-2478, 2012

Interplay of cannabinoid 2 (CB2) receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration. Journal of Molecular Medicine 90(4): 347-351, 2012

Inhibitory effects of sildenafil and tadalafil on inflammation, oxidative stress and nitrosative stress in animal model of bronchial asthma. Pharmacological Reports 71(3): 517-521, 2019

Hyperglycemia-induced inflammation caused down-regulation of 8-oxoG-DNA glycosylase levels in murine macrophages is mediated by oxidative-nitrosative stress-dependent pathways. International Journal of Biochemistry and Cell Biology 73: 82-98, 2016

Calcium Dobesilate Is Protective against Inflammation and Oxidative/Nitrosative Stress in the Retina of a Type 1 Diabetic Rat Model. Ophthalmic Research 58(3): 150-161, 2017

Mechanisms of cell death governed by the balance between nitrosative and oxidative stress. Annals of the New York Academy of Sciences 899: 209-221, 2000

Soot nanoparticles promote biotransformation, oxidative stress, and inflammation in murine lungs. American Journal of Respiratory Cell and Molecular Biology 39(2): 198-207, 2008

Integration of oxidative and nitrosative stress in the overall cell death signaling induced by sorafenib in hepatoma cells. Free Radical Biology and Medicine 96: S56-S57, 2016

Antitumoral Activity of Sorafenib in Hepatocellular Carcinoma: Effects on Cell Survival and Death Pathways, Cell Metabolism Reprogramming, and Nitrosative and Oxidative Stress. Critical Reviews in Oncogenesis 21(5-6): 413-432, 2016

PARP-1 inhibition prevents oxidative and nitrosative stress-induced endothelial cell death via transactivation of the VEGF receptor 2. Arteriosclerosis, Thrombosis, and Vascular Biology 28(4): 711-717, 2008

Nitric oxide donors rescue diabetic nephropathy through oxidative-stress-and nitrosative-stress-mediated Wnt signaling pathways. Journal of Diabetes Investigation 6(1): 24-34, 2015